CONSEQUENCES OF INVOLUNTARY SMOKING a report of the Surgeon General 1986 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES ne ERC ? yy Public Health Service z Centers for Disease Control 5 Center for Health Promotion and Education %, "ey, bei Office on Smoking and Heaith an Rockville, Maryland 20857 For sale by the Superintendent of Documents, U.S. Government Printing, Office Washington, DC 20402 THE SECRETARY OF HEALTH AND HUMAN SERVICES. WASHINGION OF 20701 DEC | 5 166 The Honorable George Bush President of the Senate Washington, D.C. 20510 Dear Mr. President: It is wy pleasure to transmit to the Congress the 1986 Surgeon General's Report on the health consequences of suoking, ae mandated by Section 8(a) of the Public Health Cigarette Smoking act of 1969. ‘The current volume, entitled The Health Consequences of involuntary Smoking, examines the scientific evidence on the health effects resulting from nonsmker exposure to environmental tobacco smke. The issue of whether or not tobacco smoke is carcinogenic for humans was conclusively resolved more than 20 years ago when the first report on smking and health was issued in 1964. Based on the current report, the judgment can now be made that exposure to environmental tobacco smoke can cause disease, including lung cancer, in nonamokers. It is also clear that simple separation of amokers and nonsmpkers within the same airspace may reduce but cannot eliminate nonswker exposure to environmental tobacco smoke. The report also reviews an extensive body of evidence which establishes ano increased risk of respiratory illness and reduced lung function in infants and very young children of parents who smoke. This effect is more pronounced if both parents smoke than if only one parent smokes. As a physician, I believe that parents should refrain from smoking around small children both as a means of protecting their children's health and to set a good example for the child. Today, only 30 percent of the adult population in the United States are smokers--the lowest level of smmking in the country since World War II, reflecting that the great majority of the population has never suoked or has successfully quit. Accompanying this decline in overall prevalence of cigarette smoking has been an increased concern for protecting the health and well being of nonsmokers, as evidenced by the number of lews and regulations restricting smoking in public places. Today, 40 States and the District of Columbia have enacted some form of legislation to restrict smoking in public. Increasingly, these laws pertain to protecting nonsmkers in many different settings, including the workplace. Based on the evidence presented in this report, the choice to smoke should mot interfere with the nonamoker's choice for an environment free of tobacco smoke. Sincerely, OC VOT ewe MZ. Otis R. Bowen, M.D. Secretary Enclosure THE SECRETARY OF HEALTH AND HUMAN SERV-LES WASH NGTON D¢ 2020, DEG OS The Honorable Thomas P. O'Neill, Jr. Speaker of the House of Representatives Washington, D.C. 20515 Dear Mr. Speaker: It is my pleasure to transmit to the Congress the 1986 Surgeon General's Report on the health consequences of smoking, as mandated by Section 8(a) of the Public Health Cigarette Smoking Act of 1969. The current volume, entitled The Health Consequences of Involuntary Smoking, examines the scientific evidence on the health effects resulting from nonsmoker exposure to environmental tobacco smke. The issue of whether or not tobacco amke is carcinogenic for humans was conclusively resolved mre than 20 years ago when the first report on smoking and health was issued in 1964. Based on the current report, the judgment can now be made that exposure to environmental tobacco smoke can cause disease, including lung cancer, in nonsmokers. It is also clear that simple separation of smokers and nonsmokers within the same airspace may reduce but cannot eliminate nonsmker exposure to environmental tobacco smoke. The report also reviews an extensive body of evidence which establishes an increased risk of respiratory illness and reduced lung function in infants and very young children of parents who smoke. This effect is more pronounced if both parents smoke than if only one parent amokes. As a physician, I believe that parents should refrain from smoking around small children both as a means of protecting their children's health and to set a good example for the child. Today, only 30 percent of the adult population in the United Statea are smkers—the lowest level of smoking in the country since World War Il, reflecting that the great majority of the population has never smked or has successfully quit. Accompanying this decline in overall prevalence of cigarette smking has been an increased concern for protecting the health and well being of nonsmokers, as evidenced by the number of laws and regulations restricting smoking in public places. Today, 40 States and the District of Columbia have enacted some form of legislation to restrict smoking in public. Increasingly, these laws pertain to protecting nonsmokers in many different settings, including the workplace. Based on the evidence presented in this report, the choice to smke should not interfere with the nonsmoker's choice for an environment free of tobacco smoke. Sincerely, OT 72-1 eevee MZ, Otis R. Bowen, M.D. Secretary Enclosure FOREWORD The data reviewed in 17 previous U.S. Public Health Service reports on the health consequences of smoking have conclusively established cigarette smoking as the largest single preventable cause of premature death and disability in the United States. The question whether tobacco smoke is harmful to smokers was answered more than 20 years ago. As a result, many scientists began to question whether the low levels of exposure to environmental tobacco smoke (ETS) received by nonsmokers could also be harmful. The current Report, The Health Consequences of Involuntary Smoking, examines the evidence that even the lower exposure to smoke received by the nonsmoker carries with it a health risk. Use of the term “involuntary smoking” denotes that for many nonsmokers, exposure to ETS is the result of an unavoidable consequence of being in proximity to smokers. It is the first Report in the health consequences of smoking series to establish a health risk due to tobacco smoke exposure for individuals other than the smoker, and represents the work of more than 60 distinguished physicians and scientists, both in this country and abroad. After careful examination of the available evidence, the following overall conclusions can be reached: 1. Involuntary smoking is a cause of disease, including lung cancer, in healthy nonsmokers. 2.The children of parents who smoke, compared with the children of nonsmoking parents, have an increased frequency of respiratory infections, increased respiratory symptoms, and slightly smaller rates of increase in lung function as the lung matures. 3. Simple separation of smokers and nonsmokers within the same air space may reduce, but does not eliminate, exposure of nonsmokers to environmental tobacco smoke. Exposure to environmental tobacco smoke occurs at home, at the worksite, in public, and in other places where smoking is permitted. vii The quality of the indoor environment must be a concern of all who control and occupy that environment. Protection of individuals from exposure to environmental tobacco smoke is therefore a responsibili- ty shared by all: e As parents and adults we must protect the health of our children by not exposing them to environmental tobacco smoke. e As employers and employees we must ensure that the act of smoking does not expose the nonsmoker to tobacco smoke. e For smokers, it is their responsibility to assure that their behavior does not jeopardize the health of others. e For nonsmokers, it is their responsibility to provide a support- ive environment for smokers who are attempting to stop. Actions taken by individuals, employers, and employee organiza- tions reflect the growing concern for protecting nonsmokers. The number of laws and regulations enacted at the national, State, and local level governing smoking in public has increased substantially over the past 10 years, and surveys conducted by numerous organizations show strong public support for these actions among both smokers and nonsmokers. As a Nation, we have made substantial progress in addressing the enormous toll inflicted by active smoking. Efforts to improve and protect individual health must be not only continued but strength- ened. On the basis of the evidence presented in this Report, it is clear that actions to protect nonsmokers from ETS exposure not only are warranted but are essential to protect public health. Robert E. Windom, M.D. Assistant Secretary for Health PREFACE This, the 1986 Report of the Surgeon General, is the U.S. Public Health Service’s 18th in the health consequences of smoking series and the 5th issued during my tenure as Surgeon General. Previous Reports have documented the tremendous health burden to society from smoking, particularly cigarette smoking. The evi- dence establishing cigarette smoking as the single largest preventa- ble cause of premature death and disability in the United States is overwhelming—totaling more than 50,000 studies from dozens of cultures. Smoking is now known to be causally related to a variety of cancers in addition to lung cancer; it is a cause of cardiovascular disease, particularly coronary heart disease, and is the major cause of chronic obstructive lung disease. It is estimated that smoking is responsible for well over 300,000 deaths annually in the United States, representing approximately 15 percent of all mortality. Thirty years ago, however, the scientific evidence linking smoking with early death and disability was more limited. By 1964, the year the Advisory Committee to the Surgeon General issued the first report on smoking and health, a substantial body of evidence had accumulated upon which a judgment could be made that smoking was a cause of disease in active smokers. Subsequent reports over the last 20 years have expanded our understanding and knowledge about smoking behavior, the toxicity and carcinogenicity of tobacco smoke, and the specific disease risks resulting from exposure to this agent. This Report is the first issued since 1964 that identifies a chronic disease risk resulting from exposure to tobacco smoke for individuals other than smokers. It is now clear that disease risk due to the inhalation of tobacco smoke is not limited to the individual who is smoking, but can extend to those who inhale tobacco smoke emitted into the air. This Report represents a detailed review of the health effects resulting from nonsmoker exposure to environmental tobacco smoke (ETS). ETS is the combination of smoke emitted from a burning tobacco product between puffs (sidestream smoke) and the smoke exhaled by the smoker. The 1986 Report, The Health Consequences of Involuntary Smoking, is a critical review of all the available scientific evidence pertaining to the health effects of ETS exposure on nonsmokers. The term “involuntary smoking” is used to ix note that such exposures often occur as an unavoidable consequence of being in close proximity to smokers. Lung Cancer and Environmental Tobacco Smoke The appropriate framework for an examination of the lung cancer risk from involuntary smoking is that of a low-dose exposure to a known human carcinogen. Over 30 years of research have conclu- sively established cigarette smoke as a carcinogen. This Report presents evidence that the chemical composition of sidestream smoke is qualitatively similar to the mainstream smoke inhaled by the active smoker, and that both mainstream and sidestream smoke act as carcinogens in bioassay systems. Data related to environmen- tal levels of tobacco smoke constituents and from measures of nicotine absorption in nonsmokers suggest that nonsmokers are exposed to levels of environmental tobacco smoke that would be expected to generate a lung cancer risk; epidemiological studies of populations exposed to ETS have documented an increased risk for lung cancer in those nonsmokers with increased exposure. It is rare to have such detailed exposure data or human epidemio- logic studies on disease occurrence when attempting to evaluate the risk of low-dose exposure to an agent with established toxicity at higher levels of exposure. The relative abundance of data reviewed in this Report, their cohesiveness, and their biologic plausibility allow a judgment that involuntary smoking can cause lung cancer in nonsmokers. Although the number of lung cancers due to involun- tary smoking is smaller than that due to active smoking, it still represents a number sufficiently large to generate substantial public health concern. It is certain that a substantial proportion of the lung cancers that occur in nonsmokers are due to ETS exposure; however, more complete data on the dose and variability of smoke exposure in the nonsmoking U.S. population will be needed before a quantitative estimate of the number of such cancers can be made. Children and Infants This Report also documents a relationship between parental smoking and the respiratory health of infants and children (under 2 years of age). Infants of parents who smoke have an increased risk of hospitalization for bronchitis and pneumonia when compared with infants of nonsmoking parents. There is a relationship between parental smoking and an increased frequency of respiratory symp- toms in children. A slower rate of growth in lung function has been observed in children of smoking parents. In many studies, if both parents smoke, a stronger relationship exists than if only one parent smokes. What future respiratory burden these findings may represent for these children later in life is not known. As a former pediatric surgeon, I strongly urge parents to refrain from smoking in the presence of children as a means of protecting not only their children’s current health status but also their own. Diseases Other Than Lung Cancer Several studies have provided data on the relationship between ETS and cancers other than lung cancer and on ETS exposure and cardiovascular disease. However, further research in these areas will be required to determine whether an association exists between ETS exposure and an increased risk of developing these diseases. Policies Restricting Smoking in Public Places The growth in our understanding of the disease risk associated with involuntary smoking has been accompanied by a change in the social acceptability of smoking and by a growing body of legislation, regulation, and voluntary action that addresses where smoking may occur in public. Forty States and the District of Columbia now have some form of legislation controlling or restricting smoking in various public settings. Some States limit smoking to only a few designated areas; however, States are increasingly developing and implement- ing comprehensive legislation that restricts smoking in many public settings, including the workplace. Nine States have restrictions that cover smoking not only by public employees but also by employees in the private sector. No systematic evaluation of the effects these measures may have on smoking behavior has been conducted, but there is little doubt that strong public sentiment exists for implementing such restric- tions. A number of national surveys conducted by voluntary health organizations, government agencies, and even the tobacco industry have documented that an overwhelming majority of both smokers and nonsmokers support restricting smoking in public. Public Health Policy and Involuntary Smoking The 1986 Surgeon General’s Report on the Health Consequences of Involuntary Smoking clearly documents that nonsmokers are placed at increased risk for developing disease as the result of exposure to environmental tobacco smoke. Critics often express that more research is required, that certain studies are flawed, or that we should delay action until more conclusive proof is produced. As both a physician and a public health xi official, it is my judgment that the time for delay is past; measures to protect the public health are required now. The scientific case against involuntary smoking as a health risk is more than sufficient to justify appropriate remedial action, and the goal of any remedial action must be to protect the nonsmoker from environmental tobacco smoke. The data contained in this Report on the rapid diffusion of tobacco smoke throughout an enclosed environment suggest that separation of smokers and nonsmokers in the same room or in different rooms that share the same ventilation system may reduce ETS exposure but will not eliminate exposure. The responsibility to protect the safety of the indoor environment is shared by all who occupy or control that environment. Changes in smoking policies regarding the workplace and other environments necessitated by the data presented in this Report should not be designed to punish the smoker. Successful implementa- tion of protection for the nonsmoker requires the support and cooperation of smokers, nonsmokers, management, and employees and should be developed through a cooperative effort of all groups affected. In addition, changes are often more effective when support and assistance is provided for the smoker who wants to quit. Cigarette smoking is an addictive behavior, and the individual smoker must decide whether or not to continue that behavior; however, it is evident from the data presented in this volume that the choice to smoke cannot interfere with the nonsmokers’ right to breathe air free of tobacco smoke. The right of smokers to smoke ends where their behavior affects the health and well-being of others; furthermore, it is the smokers’ responsibility to ensure that they do not expose nonsmokers to the potential harmful effects of tobacco smoke. C. Everett Koop, M.D. Surgeon General xii ACKNOWLEDGMENTS This Report was prepared by the Department of Health and Human Services under the general editorship of the Office on Smoking and Health, Donald R. Shopland, Acting Director. Manag- ing Editor was William R. Lynn, Acting Technical Information Officer, Office on Smoking and Health. Senior scientific editor was David M. Burns, M.D., Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of California Medical Center, San Diego, San Diego, California. Consulting scientific editors were Ellen R. Gritz, Ph.D., Director, Division of Cancer Control, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California; John H. Holbrook, M.D., Associate Professor of Internal Medicine, Department of Internal Medicine, University Hospital, Salt Lake City, Utah; and Jonathan M. Samet, M.D., Professor of Medicine, Department of Medicine, The University of New Mexico School of Medicine, Albuquerque, New Mexico. The following individuals prepared draft chapters or portions of the Report. Neal Benowitz, M.D., San Francisco General Medical Center, San Francisco, California A. Sonia Buist, M.D., Professor of Medicine, Department of Physiolo- gy, Oregon Health Sciences University, Portland, Oregon Charles Hiller, M.D., Pulmonary Division, University Hospital, Little Rock, Arkansas Dietrich Hoffmann, Ph.D., Associate Director, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York Ilse Hoffmann, Research Coordinator, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York John R. Hoidal, M.D., Director of Pulmonary Medicine, University of Tennessee Center for Health Sciences, Memphis, Tennessee John McCarthy, M.P.H., Harvard School of Public Health, Boston, Massachusetts Nancy A. Rigotti, M.D., Institute for the Study of Smoking Behavior and Policy, John F. Kennedy School of Government, Harvard University, Cambridge, Massachusetts Jonathan M. Samet, M.D., Professor of Medicine, Department of Medicine, The University of New Mexico School of Medicine, Albuquerque, New Mexico John Spengler, Ph.D., Harvard School of Public Health, Boston, Massachusetts Annetta Weber, Ph.D., Federal Institute of Technology, Zurich, Switzerland Scott T. Weiss, M.D., M.S., Associate Professor of Medicine, Chan- ning Laboratories, Harvard Medical School, Boston, Massachu- setts Anna H. Wu, Ph.D., Department of Preventive Medicine, School of Medicine, University of Southern California, Los Angeles, Califor- nia The editors acknowledge with gratitude the following distin- guished scientists, physicians, and others who lent their support in the development of this Report by coordinating manuscript prepara- tion, contributing critical reviews of the manuscript, or assisting in other ways. Elvin E. Adams, M.D., M.P.H., Director, Health and Temperance Department, General Conference of Seventh-Day Adventists, Washington, D.C. Stephen M. Ayres, M.D., Dean, School of Medicine, Medical College of Virginia, Richmond, Virginia David V. Bates, M.D.,. Professor of Medicine and Physiology, Department of Medicine, Acute Care Hospital, University of British Columbia, Vancouver, British Columbia —_ William J: Blot, Ph.D., Chief, Biostatistics Branch, Epidemiology and ‘Biostatistics Program, Division of Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Benjamin Burrows, M.D., Professor of Internal Medicine, and Director, Division of Respiratory Sciences, The University of Arizona College of Medicine, Tucson, Arizona D. M. DeMarini, Ph.D., Genetic Toxicology Division, U.S. Environ- mental Protection Agency, Research Triangle Park, North Caro- lina Vincent T. DeVita, Jr.. M.D., Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Louis Diamond, Ph.D., College of Pharmacy, University of Kentucky, Lexington, Kentucky Richard Doll, Cancer Epidemiology and Clinical Trials Unit, Imperi- al Cancer Research Fund, The Radcliffe Infirmary, University of Oxford, Oxford, England, United Kingdom xiv Manning Feinleib, M.D., Dr.P.H., Director, National Center for Health Statistics, Office of the Assistant Secretary for Health, Hyattsville, Maryland Edwin B. Fisher, Jr., Ph.D., Associate Professor, Department of Psychology, Washington University, St. Louis, Missouri William H. Foege, M.D., Executive Director, Task Force for Child Survival, Carter Presidential Center, Atlanta, Georgia Joseph F. Fraumeni, Jr., M.D., Associate Director for Epidemiology and Biostatistics, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Lawrence Garfinkel, M.A., Vice President for Epidemiology and Statistics, and Director of Cancer Prevention, American Cancer Society, New York, New York R.A. Griesemer, D.V.M., Ph.D., Director, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee Michael R. Guerin, Ph.D., Organic Chemistry Section, Analytical Chemistry, Oak Ridge National Laboratory, Oak Ridge, Tennessee Jeffery E. Harris, M.D., Ph.D., Associate Professor, Department of Economics, Massachusetts Institute of Technology, Cambridge, Massachusetts Millicent Higgins, M.D., Associate Director, Epidemiology and Biometry Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Takeshi Hirayama, M.D., Director, Institute of Preventive Oncology, Shinjuku-ku, Tokyo, Japan Dwight Janerich, D.D.S., M.P.H., Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut Martin Jarvis, M.P.H., Senior Clinical Psychologist, Addiction Research Unit, Institute of Psychiatry, London, England, United Kingdom Brian P. Leaderer, Ph.D., M.P.H., Associate Fellow, John B. Pierce Foundation Laboratory, Associate Professor, Department of Epide- miology and Public Health, Yale University School of Medicine, New Haven, Connecticut Charles L. LeMaistre, M.D., President, University of Texas Systems Cancer Center, Houston, Texas Claude Lenfant, M.D., Director, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Donald Ian Macdonald, M.D., Administrator, Alcohol, Drug Abuse, and Mental Health Administration, Rockville, Maryland James 8. Marks, M.D., M.P.H., Assistant Director for Science, Center for Health Promotion and Education, Centers for Disease Control, Atlanta, Georgia James O. Mason, M.D., Dr.P.H., Director, Centers for Disease Control, Atlanta, Georgia xv J. Michael McGinnis, M.D., Deputy Assistant Secretary for Health (Disease Prevention and Health Promotion), Office of the Assistant Secretary for Health, Washington, D.C. A. J. McMichael, M.D., M.B.B.S., Ph.D., Chairman and Senior Principal Research Scientist, CSIRO Division of Human Nutrition, Adelaide, South Australia D. J. Moschandreas, Ph.D., Research Director, ITT Research Insti- tute, Chicago, Illinois David Muir, M.D., Director, Occupational Health Program, Health Sciences Center, McMaster University, Hamilton, Ontario, Cana- da C. Tracy Orleans, Ph.D., Research Associate, Health Services Re- search Center, University of North Carolina, Chapel Hill, North Carolina Richard Peto, M.A., M.Sc., LC.R.F., Regius Assessor of Medicine, The Radcliffe Infirmary, University of Oxford, Oxford, England, Unit- ed Kingdom Otto Raabe, M.D., Laboratory for Energy Related Health Research, University of California, Davis, Davis, California James L. Repace, Chief of Technical Services, Indoor Air Quality Program, U.S. Environmental Protection Agency, Washington, D.C. M.A.H. Russell, F.R.C.P., Addiction Research Unit, Institute of Psychiatry, University of London, London, England, United King- dom Roy J. Shephard, M.D., Ph.D., Director, School of Physical and Health Education, University of Toronto, Toronto, Canada Frank E. Speizer, M.D., Channing Laboratories, Harvard Medical School, Boston, Massachusetts Jesse L. Steinfeld, M.D., President, Medical College of Georgia, Augusta, Georgia David N. Sundwall, M.D., Administrator, Health Resources and Services Administration, Rockville, Maryland Gregory W. Traynor, Staff Scientist, Lawrence Berkeley Laboratory, Berkeley, California Dimitrios Trichopoulos, Director, Department of Hygiene and Epide- miology, School of Medicine, University of Athens, Athens, Greece Kenneth E. Warner, Ph.D., Professor, and Chairman, Department of Public Health Policy and Administration, School of Public Health, The University of Michigan, Ann Arbor, Michigan Ernst L. Wynder, M.D., President, American Health Foundation, New York, New York James B. Wyngaarden, M.D., Director, National Institutes of Health, Bethesda, Maryland Frank E. Young, M.D., Commissioner, Food and Drug Administra- tion, Rockville, Maryland The editors also acknowledge the contributions of the following staff members and others who assisted in the preparation of this Report. Erica W. Adams, Chief Copy Editor and Assistant Production Manager, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Maryland Richard H. Amacher, Director, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Maryland Margaret L. Anglin, Secretary, Office on Smoking and Health, Rockville, Maryland John L. Bagrosky, Associate Director for Program Operations, Office on Smoking and Health, Rockville, Maryland Charles A. Brown, Programmer, Automation and Technical Services Department, Sterling Software, Inc., Rockville, Maryland Clarice D. Brown, Statistician, Office on Smoking and Health, Rockville, Maryland Richard C. Brubaker, Information Specialist, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Catherine E. Burckhardt, Secretary, Office on Smoking and Health, Rockville, Maryland Joanna B. Crichton, Copy Editor, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Maryland Stephanie D. DeVoe, Programmer, Automation and Technical Services Department, Sterling Software, Inc., Rockville, Maryland Danny A. Goodman, Information Specialist, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Patricia E. Healy, Technical Information Specialist, Office on Smoking and Health, Rockville, Maryland Terri L. Henry, Clerk-Typist, Office on Smoking and Health, Rockville, Maryland Timothy K. Hensley, Technical Publications Writer, Office on Smoking and Health, Rockville, Maryland Shirley K. Hickman, Data Entry Operator, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Robert S. Hutchings, Associate Director for Information and Pro- gram Development, Office on Smoking and Health, Rockville, Maryland Maureen Illar, Editorial Assistant, Office on Smoking and Health, Rockville, Maryland Julie Kurz, Graphic Artist, Information Center Management De- partment, Sterling Software, Inc., Rockville, Maryland Ruth C. Palmer, Secretary, Office on Smoking and Health, Rockville, Maryland xvii Jerome A. Paulson, M.D., Medical Officer, Office on Smoking and Health, Rockville, Maryland Russell D. Peek, Library Acquisitions Specialist, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Margaret E. Pickerel, Public Information and Publications Special- ist, Office on Smoking and Health, Rockville, Maryland Raymond K. Poole, Production Coordinator, Health and Natural Resources Department, Sterling Software, Inc., Rockville, Mary- land Linda R. Spiegelman, Administrative Officer, Office on Smoking and Health, Rockville, Maryland Evelyn L. Swarr, Administrative Secretary, Automation and Techni- cal Services Department, Sterling Software, Inc., Rockville, Mary- land Debra C. Tate, Publications Systems Specialist, Publishing Systems Division, Sterling Software, Inc., Riverdale, Maryland Jerry W. Vaughn, Programmer, University of California, San Diego, San Diego, California Mary I. Walz, Computer Systems Analyst, Office on Smoking and Health, Rockville, Maryland Louise G. Wiseman, Technical Information Specialist, Office on Smoking and Health, Rockville, Maryland Pamela Zuniga, Secretary, University of California, San Diego, San Diego, California xviii TABLE OF CONTENTS Foreword ........ccceccccecccasc ee ene een eee see enna ee ee eee ee en eeee nae vii PLefACE oc cece cece cece cece eee eee e nent een EES ENOL REET e EEE E EASES ED ix Acknowledgments.............c::csseeeeseeeeeneeeeereeeenenenreees xiii 1. Introduction, Overview, and Summary and Conclusions ..........c.ccceeceececececensenaeeneenseeneeesennenees 1 2. Health Effects of Environmental Tobacco Smoke Ex- POSUIC 2... ccc ee cece eee c ee nenenene nee none eee ee eens nena nt eas 17 3. Environmental Tobacco Smoke Chemistry and Expo- sures of Nonsmokers ...........-..-.0ceseceeeeeeessceeeeraes 121 4. Deposition and Absorption of Tobacco Smoke Constit- UCNES 20... cc ccccc cece ce ccccccceeneeeee ee eeesesceeene nese eee tenene 177 5. Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke .............:::02006 225 6. Policies Restricting Smoking in Public Places and the Workplace. .........cccccseeeeeeecesceee eens eeeeeeeneceenen senses 261 CHAPTER 1 INTRODUCTION, OVERVIEW, AND SUMMARY AND CONCLUSIONS CONTENTS Introduction Development and Organization of the 1986 Report Overview Environmental Tobacco Smoke Constitutents Extent of Exposure Lung Cancer Respiratory Disease Cardiovascular Disease Irritation Determinants of Exposure Policies Restricting Smoking Summary and Conclusions of the 1986 Report Health Effects of Environmental Tobacco Smoke Exposure Environmental Tobacco Smoke Chemistry and Exposures of Nonsmokers Deposition and Absorption of Tobacco Smoke Constit- uents Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke Policies Restricting Smoking in Public Places and the Workplace Introduction Development and Organization of the 1986 Report The 1986 Report was developed by the Office on Smoking and Health of the U.S. Department of Health and Human Services as part of the Department’s responsibility, under Public Law 91-222, to report new and current information on smoking and health to the United States Congress. The scientific content of this Report reflects the contributions of more than 60 scientists representing a variety of disciplines. Individual manuscripts were written by experts known for their understanding of and work in specific content areas. These manu- scripts were refined through a series of meetings attended by the authors, Office on Smoking Health staff and consultants, and the Surgeon General. Upon receipt of the final manuscripts from the authors, the Office and its consultants edited and consolidated the individual manu- scripts into appropriate chapters. These draft chapters were subjec- ted to an extensive outside peer review (see Acknowledgments for individuals and their affiliations) whereby each was reviewed by up to seven experts. Their comments were integrated and the entire volume was assembled. This revised edition of the Report was resubjected to review by 17 distinguished scientists outside the Federal Government, both in this country and abroad. Parallel to this review, the entire Report was also submitted to various institutes and agencies within the U.S. Public Health Service for review and comment. The 1986 Report contains a Foreword by the Assistant Secretary for Health, a Preface by the Surgeon General of the US. Public Health Service, and the following chapters: Chapter 1. Introduction, Overview, and Summary and Conclu- sions Chapter 2. Health Effects of Environmental Tobacco Smoke Exposure Chapter 3. Environmental Tobacco Smoke Chemistry and Expo- sures of Nonsmokers Chapter 4. Deposition and Absorption of Tobacco Smoke Constit- uents Chapter 5. Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke Chapter 6. Policies Restricting Smoking in Public Places and the Workplace Overview Inhalation of tobacco smoke during active cigarette smoking remains the largest single preventable cause of death and disability 5 for the U.S. population. The health consequences of cigarette smoking and of the use of other tobacco products have been extensively documented in the 17 previous Reports in the health consequences of smoking series issued by the U.S. Public Health Service. Cigarette smoking is a major cause of cancer; it is most strongly associated with cancers of the lung and respiratory tract, but also causes cancers at other sites, including the pancreas and urinary bladder. It is the single greatest cause of chronic obstructive lung diseases. It causes cardiovascular diseases, including coronary heart disease, aortic aneurysm, and atherosclerotic peripheral vascular disease. Maternal cigarette smoking endangers fetal and neonatal health; it contributes to perinatal mortality, low birth weight, and complications during pregnancy. More than 300,000 premature deaths occur in the United States each year that are directly attributable to tobacco use, particularly cigarette smoking. This Report examines in detail the scientific evidence on involun- tary smoking as a potential cause of disease in nonsmokers. Nonsmokers’ exposure to environmental tobacco smoke is termed involuntary smoking in this Report because the exposure generally occurs as an unavoidable consequence of being in proximity to smokers, particularly in enclosed indoor environments. The term “passive smoking” is also used throughout the scientific literature to describe this exposure. The magnitude of the disease risks for active smokers secondary to their “high dose” exposure to tobacco smoke suggests that the “lower dose” exposure to tobacco smoke received by involuntary smokers may also have risks. Although the risks of involuntary smoking are smaller than the risks of active smoking, the number of individuals injured by involuntary smoking is large both in absolute terms and in comparison with the number injured by some other agents in the general environment that are regulated to curtail their potential to cause human illness. This Report reviews the evidence on the characteristics of main- stream tobacco smoke and of environmental tobacco smoke, on the levels of exposure to environmental tobacco smoke that occur, and on the health effects of involuntary exposure to tobacco smoke. The composition of the tobacco smoke inhaled by active smokers and by involuntary smokers is examined for similarities and differences, and the concentrations of tobacco smoke components that can be measured in a variety of settings are explored, as is smoke deposition and absorption in the respiratory tract. The studies that describe the risks of environmental tobacco smoke exposure for humans are carefully reviewed for their findings and their validity. The evidence on the health effects of involuntary smoking is reviewed for biologic plausibility, and compared with extrapolations of the risks of active 6 smoking to the lower dose of exposure to tobacco smoke found in nonsmokers. This review leads to three major conclusions: 1. Involuntary smoking is a cause of disease, including lung cancer, in healthy nonsmokers. 2. The children of parents who smoke compared with the children of nonsmoking parents have an increased frequency of respiratory infections, increased respira- tory symptoms, and slightly smaller rates of increase in lung function as the lung matures. 3. The simple separation of smokers and nonsmokers within the same air space may reduce, but does not eliminate, the exposure of nonsmokers to environmen- tal tobacco smoke. The subsequent chapters of this volume describe in detail the evidence that supports these conclusions; the evidence is briefly summarized here. Environmental Tobacco Smoke Constituents Important considerations in examining the risks of involuntary smoking are the composition of environmental tobacco smoke (ETS) and its toxicity and carcinogenicity relative to the tobacco smoke inhaled by active smokers. Mainstream cigarette smoke is the smoke drawn through the tobacco into the smoker’s mouth. Sidestream smoke is the smoke emitted by the burning tobacco between puffs. Environmental tobacco smoke results from the combination of sidestream smoke and the fraction of exhaled mainstream smoke not retained by the smoker. In contrast with mainstream smoke, ETS is diluted into a larger volume of air, and it ages prior to inhalation. The comparison of the chemical composition of the smoke inhaled by active smokers with that inhaled by involuntary smokers suggests that the toxic and carcinogenic effects are qualitatively similar, a similarity that is not too surprising because both mainstream smoke and environmental tobacco smoke result from the combustion of tobacco. Individual mainstream smoke constituents, with appropri- ate testing, have usually been found in sidestream smoke as well. However, differences between sidestream smoke and mainstream smoke have been well documented. The temperature of combustion during sidestream smoke formation is lower than during main- stream smoke formation. As a result, greater amounts of many of the organic constituents of smoke, including some carcinogens, are generated when tobacco burns and forms sidestream smoke than when mainstream smoke is produced. For example, in contrast with mainstream smoke, sidestream smoke contains greater amounts of ammonia, benzene, carbon monoxide, nicotine, and the carcinogens 7 2-napthylamine, 4-aminobiphenyl, N-nitrosamine, benz{a} anthracene, and benzo-pyrene per milligram of tobacco burned. Although only limited bioassay data comparing mainstream smoke and sidestream smoke are available, one study has suggested that sidestream smoke may be more carcinogenic. Extent of Exposure Although sidestream smoke and mainstream smoke differ some- what qualitatively, the differing quantitative doses of smoke compo- nents inhaled by the active smoker and by the involuntary smoker are of greater importance in considering the risks of the two exposures. A number of different markers for tobacco smoke exposure and absorption have been identified for both active and involuntary smoking. No single marker quantifies, with precision, the exposure to each of the smoke constituents over the wide range of environmental settings in which involuntary smoking occurs. However, in environments without other significant sources of dust, respirable suspended particulate levels can be used as a marker of smoke exposure. Levels of nicotine and its metabolite cotinine in body fluids provide a sensitive and specific indication of recent whole smoke exposure under most conditions. Widely varying levels of environmental tobacco smoke can be measured in the home and other environments using markers. The time-activity patterns of nonsmokers, which indicate the time spent in environments containing ETS, also vary widely. Thus, the extent of exposure to ETS is probably highly variable among individuals at a given point in time, and little is known about the variation in exposure of the same individual at different points in time. Lung Cancer The American Cancer Society estimates that there will be more than 135,000 deaths from lung cancer in the United States in 1986, and 85 percent of these lung cancer deaths are directly attributable to active cigarette smoking. Therefore, even if the number of lung cancer deaths caused by involuntary smoking were much smaller than the number of lung cancer deaths caused by active smoking, the number of lung cancer deaths attributable to involuntary exposure would still represent a problem of sufficient magnitude to warrant substantial public health concern. Exposure to environmental tobacco smoke has been examined in numerous recent epidemiological studies as a risk factor for lung cancer in nonsmokers. These studies have compared the risks for subjects exposed to ETS at home or at work with the risks for people not reported to be exposed in these environments. Because exposure to ETS is an almost universal experience in the more developed countries, these studies involve comparison of more exposed and less 8 exposed people rather than comparison of exposed and unexposed people. Thus, the studies are inherently conservative in assessing the consequences of exposure to ETS. Interpretation of these studies must consider the extent to which populations with different ETS exposures have been identified, the gradient in ETS exposure from the lower exposure to the higher exposure groups, and the magni- tude of the increased lung cancer risk that results from the gradient in ETS exposure. To date, questionnaires have been used to classify ETS exposure. Quantification of exposure by questionnaire, particularly lifetime exposure, is difficult and has not been validated. However, spousal and parental smoking status identify individuals with different levels of exposure to ETS. Therefore, investigation has focused on the children and nonsmoking spouses of smokers, groups for whom greater ETS exposure would be expected and for whom increased nicotine absorption has been documented relative to the children and nonsmoking spouses of nonsmokers. Of the epidemiologic studies reviewed in this Report that have examined the question of involuntary smoking’s association with lung cancer, most (11 of 13) have ‘shown a positive association with exposure, and in 6 the association reached statistical significance. Given the difficulty in identifying groups with differing ETS exposure, the low-dose range of exposure examined, and the small numbers of subjects in some series, it is not surprising that some studies have found no association and that in others the association did not reach a conventional level of statistical significance. The question is not whether cigarette smoke can cause lung cancer; that question has been answered unequivocally by examining the evi- dence for active smoking. The question is, rather, can tobacco smoke at a lower dose and through a different mode of exposure cause lung cancer in nonsmokers? The answer must be sought in the coherence and trends of the epidemiologic evidence available on this low-dose exposure to a known human carcinogen. In general, those studies with larger population sizes, more carefully validated diagnosis of lung cancer, and more careful assessment of ETS exposure status have shown statistically significant associations. A number of these studies have demonstrated a dose-response relationship between the level of ETS exposure and lung cancer risk. By using data on nicotine absorption by the nonsmoker, the nonsmoker’s risk of developing lung cancer observed in human epidemiologic studies can be compared with the level of risk expected from an extrapolation of the dose-response data for the active smoker. This extrapolation yields estimates of an expected lung cancer risk that approximate the observed lung cancer risk in epidemiologic studies of involuntary smoking. Cigarette smoke is well established as a human carcinogen. The chemical composition of ETS is qualitatively similar to mainstream smoke and sidestream smoke and also acts as a carcinogen in bioassay systems. For many nonsmokers, the quantitative exposure to ETS is large enough to expect an increased risk of lung cancer to occur, and epidemiologic studies have demonstrated an increased lung cancer risk with involuntary smoking. In examining a low-dose exposure to a known carcinogen, it is rare to have such an abundance of evidence on which to make a judgment, and given this abundance of evidence, a clear judgment can now be made: exposure to ETS is a cause of lung cancer. The data presented in this Report establish that a substantial number of the lung cancer deaths that occur among nonsmokers can be attributed to involuntary smoking. However, better data on the extent and variability of ETS exposure are needed to estimate the number of deaths with confidence. Respiratory Disease Acute and chronic respiratory diseases have also been linked to involuntary exposure to tobacco smoke; the evidence is strongest in infants. During the first 2 years of life, infants of parents who smoke are more likely than infants of nonsmoking parents to be hospital- ized for bronchitis and pneumonia. Children whose parents smoke also develop respiratory symptoms more frequently, and they show small, but measurable, differences on tests of lung function when compared with children of nonsmoking parents. Respiratory infections in young children represent a direct health burden for the children and their parents; moreover, these infec- tions, and the reductions in pulmonary function found in the school- age children of smokers, may increase susceptibility to develop lung disease as an adult. Several studies have reported small decrements in the average level of lung function in nonsmoking adults exposed to ETS. These ifferences may represent a response of the lung to chronic exposure to the irritants in ETS, but it seems unlikely that ETS exposure, by itself, is responsible for a substantial number of cases of clinically significant chronic obstructive lung disease. The small magnitude of the changes associated with ETS exposure suggests that only individuals with unusual susceptibility would be at risk of develop- ing clinically evident disease from ETS exposure alone. However, ETS exposure may be a factor that contributes to the development of clinical disease in individuals with other causes of lung injury. Cardiovascular Disease A few studies have examined the relationship between inv t ¢ olun- tary smoking and cardiovascular disease, but no firm conclusion on 10 the relationship can be made owing to the limited number of deaths in the studies. Irritation Perhaps the most common effect of tobacco smoke exposure is tissue irritation. The eyes appear to be especially sensitive to irritation by ETS, but the nose, throat, and airway may also be affected by smoke exposure. Irritation has been demonstrated to occur at levels that are similar to those found in real-life situations. The level of irritation increases with an increasing concentration of smoke and duration of exposure. In addition, participants in surveys report irritation and annoyance due to smoke in the environment under real-life conditions. Determinants of Exposure Exposure to ETS has been documented to be common in the United States, but additional data on the extent and determinants of exposure are needed to identify individuals within the population who have the highest exposure and are at greatest risk. Studies with biological markers and measurements of ETS components in indoor air confirm that measurable exposure to ETS is widespread. How- ever, within exposed populations, levels of cotinine excretion and presumably ETS exposure vary greatly. In a room or other indoor area, the size of the space, the number of smokers, the amount of ventilation, and other factors determine the concentration of tobacco smoke in the air. The technology for the cost-effective filtration of tobacco smoke from the air is not currently available, and because of their small size, the smoke particles remain suspended in the air for long periods of time; thus, the only way to remove smoke from indoor air is to increase the exchange of indoor air with clean outdoor air. The number of air changes per hour required to maintain acceptable indoor air quality is much higher when smoking is allowed than when smoking is prohibited. Environmental tobacco smoke originates at the lighted tip of the cigarette, and exposure to ETS is greatest in proximity to the smoker. However, the smoke rapidly disseminates throughout any airspace contiguous with the space in which the smoking is taking place. Dissemination of smoke is not uniform, and substantial gradients in ETS levels have been demonstrated in different parts of the same airspace. The time course of tobacco smoke dissemination is rapid enough to ensure the spread of smoke throughout an airspace within an 8-hour workday. In the home, the presence of even one smoker can significantly increase levels of respirable suspended particulates. These data lead to the conclusion that the simple separation of smokers and nonsmokers within the same airspace will reduce, but 11 not eliminate, exposure to ETS, particularly in those settings where exposure is prolonged, such as the working environment. The exposure of an individual nonsmoker to ETS is also deter- mined by that person’s time-activity pattern; that is, the amount of time spent in various locations. For adults, the duration of time spent in smoke-contaminated environments at work or at home is the principal determinant of ETS exposure, along with the levels of smoke in those environments. For infants and very young children, the smoking habit of the primary. caretaker, as well as that person’s time-activity pattern, is likely to play a major role in determining ETS exposure. Policies Restricting Smoking Policies regulating cigarette smoking with the objective of reduc- ing explosion or fire risk, or of safeguarding the quality of manufac- tured products, have been in force in a number of States since the late 1800s. More recently, and with steadily increasing frequency, policies regulating smoking on the basis of the health risk or the irritation of involuntary smoking have been promulgated. State and local governments have enacted laws and regulations restricting smoking in public places. These policies have been implemented with few problems and at little cost to the respective governments. The public awareness of these policies that results from the media coverage surrounding their implementation proba- bly facilitates their self-enforcement. Public awareness may best be fostered by encouraging the establishment of these changes at the local level. Policies limiting smoking in the worksite have also become increasingly widespread and more restrictive. However, changes in worksite policies have evolved largely through voluntary rather than governmental action. In a steadily increasing number of worksites, smoking has been prohibited completely or limited to relatively few areas within the worksite. The creation of a smoke- free workplace has proceeded successfully when the policy has been jointly developed by employees, employee organizations, and man- agement; instituted in phases; and accompanied by support and assistance for the smokers to quit smoking. This trend to protect nonsmokers from ETS exposure may have an added public health benefit—helping those smokers who are at- tempting to quit to be more successful and not encouraging smoking by people entering the workforce. Summary and Conclusions of the 1986 Report The three major conclusions of this report are the following: 12 1. Involuntary smoking is a cause of disease, including lung cancer, in healthy nonsmokers. 2. The children of parents who smoke compared with the children of nonsmoking parents have an increased frequency of respiratory infections, increased respira- tory symptoms, and slightly smaller rates of increase in lung function as the lung matures. 3. The simple separation of smokers and nonsmokers within the same air space may reduce, but does not _ eliminate, the exposure of nonsmokers to environmen- tal tobacco smoke. Individual chapter summaries and conclusions follow. Health Effects of Environmental Tobacco Smoke Exposure 1. Involuntary smoking can cause lung cancer in nonsmokers. 2. Although a substantial number of the lung cancers that occur in nonsmokers can be attributed to involuntary smoking, more data on the dose and distribution of ETS exposure in the population are needed in order to accurately estimate the magnitude of risk in the U.S. population. 3. The children of parents who smoke have an increased frequen- cy of hospitalization for bronchitis and pneumonia during the first year of life when compared with the children of nonsmok- ers. 4, The children of parents who smoke have an increased frequen cy of a variety of acute respiratory illnesses and infections, including chest illnesses before 2 years of age and physician- diagnosed bronchitis, tracheitis, and laryngitis, when com- pared with the children of nonsmokers. 5. Chronic cough and phlegm are more frequent in children whose parents smoke compared with children of nonsmokers. The implications of chronic respiratory symptoms for respira- tory health as an adult are unknown and deserve further study. 6. The children of parents who smoke have small differences in tests of pulmonary function when compared with the children of nonsmokers. Although this decrement is insufficient to cause symptoms, the possibility that it may increase suscepti- bility to chronic obstructive pulmonary disease with exposure to other agents in adult life, e.g., active smoking or occupation- al exposures, needs investigation. 7. Healthy adults exposed to environmental tobacco smoke may have small changes on pulmonary function testing, but are unlikely to experience clinically significant deficits in pulmo- 13 nary function as a result of exposure to environmental tobacco smoke alone. 8. A number of studies report that chronic middle ear effusions are more common in young children whose parents smoke than in children of nonsmoking parents. 9. Validated questionnaires are needed for the assessment of recent and remote exposure to environmental tobacco smoke in the home, workplace, and other environments. 10. The associations between cancers, other than cancer of the lung, and involuntary smoking require further investigation before a determination can be made about the relationship of involuntary smoking to these cancers. 11. Further studies on the relationship between involuntary smoking and cardiovascular disease are needed in order to determine whether involuntary smoking increases the risk of cardiovascular disease. Environmental Tobacco Smoke Chemistry and Exposures of Nonsmokers 1. Undiluted sidestream smoke is characterized by significantly higher concentrations of many of the toxic and carcinogenic compounds found in mainstream smoke, including ammonia, volatile amines, volatile nitrosamines, certain nicotine decom- position products, and aromatic amines, 2. Environmental tobacco smoke can be a substantial contributor to the level of indoor air pollution concentrations of respirable particles, benzene, acrolein, N-nitrosamine, pyrene, and carbon monoxide. ETS is the only source of nicotine and some N- nitrosamine compounds in the general environment. 3. Measured exposures to respirable suspended particulates are higher for nonsmokers who report exposure to environmental tobacco smoke. Exposures to ETS occur widely ‘in the non- smoking population. 4. The small particle size of environmental tobacco smoke places it in the diffusion-controlled regime of movement in air for deposition and removal mechanisms. Because these submicron particles will follow air streams, convective currents will dominate and the distribution of ETS will occur rapidly through the volume of a room. As a result, the simple Separation of smokers and nonsmokers within the same airspace may reduce, but will not eliminate, exposure to ETS. 5. It has been demonstrated that ETS has resulted in elevated respirable suspended particulate levels in enclosed places. 14 Deposition and Absorption of Tobacco Smoke Constituents 1. Absorption of tobacco-specific smoke constituents (i.e., nicotine) from environmental tobacco smoke exposures has been docu- mented in a number of samples of the general population of developed countries, suggesting that measurable exposure to environmental tobacco smoke is common. 2. Mean levels of nicotine and cotinine in body fluids increase with self-reported ETS exposure. 3. Because of the stability of cotinine levels measured at different times during exposure and the availability of noninvasive sampling techniques, cotinine appears to be the short-term marker of choice in epidemiological studies. 4. Both mathematical modeling techniques and experimental data suggest that 10 to 20 percent of the particulate fraction of sidestream smoke would be deposited in the airway. 5. The development of specific chemical assays for human expo- sure to the components of cigarette tar is an important research goal. Toxicity, Acute Irritant Effects, and Carcinogenicity of Environmental Tobacco Smoke 1. The main effects of the irritants present in ETS occur in the conjunctiva of the eyes and the mucous membranes of the nose, throat, and lower respiratory tract. These irritant effects are a frequent cause of complaints about poor air quality due to environmental tobacco smoke. 2. Active cigarette smoking is associated with prominent changes in the number, type, and function of respiratory epithelial and inflammatory cells; the potential for environmental tobacco smoke exposure to produce similar changes should be investi- gated. 3. Animal models have demonstrated the carcinogencity of ciga- rette smoke, and the limited data that exist suggest that more carcinogenic activity per milligram of cigarette smoke concen- trate may be contained in sidestream smoke than in main- stream cigarette smoke. Policies Restricting Smoking in Public Places and the Workplace 1. Beginning in the 1970s, an increasing number of public and private sector institutions have adopted policies to protect individuals from environmental tobacco smoke exposure by restricting the circumstances in which smoking is permitted. 2.Smoking in public places has been regulated primarily by government actions, which have occurred at Federal, State, 15 16 and local levels. All but nine States have enacted laws regulating smoking in at least one public place. Since the mid- 1970s, there has been an increase in the rate of enactment and in the comprehensiveness of State legislation. Local govern- ments have enacted smoking ordinances at an increasing rate since 1980; more than 80 cities and counties have smoking laws in effect. 3. Smoking at the workplace is regulated by a combination of government action and private initiative. Legislation in 12 States regulates smoking by government employees, and 9 States and more than 70 communities regulate smoking in the private sector workplace. Approximately 35 percent of busi- nesses have adopted smoking policies. The increase in work- place smoking policies has been a trend of the 1980s. 4. Smoking policies may have multiple effects. In addition to reducing environmental tobacco smoke exposure, they may alter smoking behavior and public attitudes about tobacco use. Over time, this may contribute to a reduction in smoking in the United States. To the present, there has been relatively little systematic evaluation of policies restricting smoking in public places or at the workplace. 5. On the basis of case reports and a small number of systematic studies, it appears that workplace smoking policies improve air quality, are met with good compliance, and are well accepted by both smokers and nonsmokers. Policies appear to be followed by a decrease in smokers’ cigarette consumption at work and an increase in enrollment in company-sponsored smoking cessation programs. 6. Laws restricting smoking in public places have been imple- mented with few problems and at little cost to State and local government. Their impact on smoking behavior and attitudes has not yet been evaluated. 7. Public opinion polls document strong and growing support for restricting or banning smoking in a wide range of public places. Changes in attitudes about smoking in public appear to have preceded legislation, but the interrelationship of smoking attitudes, behavior, and legislation are complex. CHAPTER 2 HEALTH EFFECTS OF ENVIRONMENTAL TOBACCO SMOKE EXPOSURE CONTENTS Introduction Evaluation of Low-Dose Tobacco Smoke Exposures Extrapolation of Active Smoking Data to Environ- mental Tobacco Smoke Exposure Comparison of Mainstream Smoke and Side- stream Smoke Deposition of Mainstream Smoke and Side- stream Smoke and Environmental Tobacco Smoke Dose Estimates _ Dose-Response Relationships and Threshold for Risk Pathophysiologic Considerations Cancer Lung Disease Methodological Considerations in Epidemiologic Studies Measurement of Exposure Atmospheric Markers Personal Monitoring Questionnaires Measurements of Absorption Potentially Confounding Variables Statistical Issues Respiratory System Effects of Involuntary Cigarette Smoke Exposure Infants and Children Acute Respiratory Illness Longitudinal Studies Cross-Sectional Studies Case-Control Studies Cough, Phiegm, and Wheezing Pulmonary Function Bronchoconstriction Ear, Nose, and Throat Adults Acute Respiratory Ilness Cough, Phlegm, and Wheezing 19 Pulmonary Function Bronchoconstriction Normal Subjects Asthmatics Ear, Nose, and Throat Lung Cancer Observed Risk General Methodological Issues Spousal Exposure: Prospective Studies The Japanese Cohort Study The American Cancer Society Cohort Study The Scottish Study Spousal Exposure: Case-Control Studies The Greek Study The Louisiana Study The Hong Kong Studies An Ongoing Study of Tobacco-Related Cancers The Los Angeles County Study The Four Hospitals Study A United Kingdom Study The Japanese Case-Control Study The Swedish Study The German Study Other Sources of Tobacco Smoke Exposure Parental Smoking Coworker’s Smoking Dose-Response Relationship Expected Lung Cancer Risk Summary Other Cancers Cardiovascular Diseases Conclusions References Introduction In 1964, the first Report of the Surgeon General on smoking and health (US PHS 1964) determined that cigarette smoking was a cause of lung cancer in men and probably a cause of lung cancer in women. That Report also noted causal relationships between smok- ing and other cancers, as well as chronic lung disease. Subsequent Reports have described associations, both causal and noncausal, between tobacco smoking and a wide range of acute and chronic diseases. Epidemiological investigations have documented the effects of tobacco smoking in humans; complementary laboratory investiga- tions have elucidated some of the mechanisms through which tobacco smoke causes disease. More recently, the effects of the inhalation of environmental tobacco smoke by nonsmokers have become a pressing public health concern. Nonsmokers, as well as active smokers, inhale environmen- tal tobacco smoke, the mixture of sidestream smoke and exhaled mainstream smoke. Various terms have been applied to the inhala- tion of environmental tobacco smoke by nonsmokers; the terms “involuntary smoking” and “passive smoking” are the most preva- lent and are often used interchangeably by researchers and the public. Many of the known toxic and carcinogenic agents found in mainstream cigarette smoke have also been demonstrated to be present in sidestream smoke. Furthermore, the combustion condi- tions under which sidestream smoke is produced result in the generation of larger amounts of many of these toxic and carcinogenic agents per gram of tobacco burned than the conditions under which mainstream smoke is generated (see Chapter 3). The characteristics of environmental tobacco smoke also differ from those of main- stream smoke because the sidestream smoke ages before it is inhaled and the mainstream smoke exhaled by the active smoker is modified during its residence in the lung. There is no evidence to suggest that environmental tobacco smoke has a qualitatively lower toxicity or carcinogenicity than mainstream smoke per milligram of smoke inhaled. In fact, the available evidence suggests that sidestream smoke contains higher concentrations of many known toxic and carcinogenic agents per milligram of smoke and is more tumorgenic than mainstream smoke in animal testing (Wynder and Hoffmann 1967). As a result, involuntary smoking should not be viewed as a qualitatively different exposure from active smoking, but rather as a low-dose exposure to a known hazardous agent—cigarette smoke. Evaluation of Low-Dose Tobacco Smoke Exposures Assessment of the health effects of any environmental exposure poses methodological problems, particularly when exposure levels 21 are low and therefore the magnitude of the expected effect is small. The evaluation of an effect due to a low-dose exposure such as environmental tobacco smoke requires the investigation of popula- tions with differences in exposure large enough so that an effect could be anticipated. The population studied must also be of sufficient size to quantitate the effects in the range of interest with precision. Failure to fulfill these requirements may produce a false- negative result in a study of a low-dose exposure. Exposure to environmental tobacco smoke is a nearly universal experience in the more developed countries, so the identification of a truly unexposed population is very difficult. Epidemiological studies of involuntary smoking have attempted to identify populations with lower exposure and higher exposure to environmental tobacco smoke, most notably by examining nonsmokers exposed to tobacco smoke generated by the smokers of their family. The effects of environmental tobacco smoke have been investigated in a number of populations throughout the world. The diversity of these populations is likely to be accompanied by a similar diversity of their exposure to environmental tobacco smoke. Thus, the gradient in exposure to environmental tobacco smoke between the “exposed” and “nonex- posed” groups is likely to vary widely among the reported studies. For example, the husband’s smoking status may be a strong predictor of total exposure to ETS in traditional societies, such as Japan and Greece, where the wife’s exposure outside the home is limited. In contrast, the husband’s smoking status in the United States, where substantial exposure may occur outside the home, may not be as predictive. epidemiological studies of lung cancer and involuntary smoking. Because the frequency of lung cancer in nonsmokers is low, many of these studies often included small numbers of nonsmokers and involuntary smoking, as the basis for its conclusions. In evaluating the hazards posed by an air pollutant such as environmental tobacco smoke, laboratory, toxicological, human exposure, and epidemiological investigations provide relevant data. Each approach has limitations, but the insights each provides are complementary. Epidemiological investigations describe the effects 22 in human populations, but their results must be interpreted in the context of the other types of investigations. Risk assessment techniques have also been used to characterize the potential adverse health effects of human exposures to environ- mental pollutants, particularly those at low levels. The four steps of risk assessment have been described by the National Academy of Sciences as hazard identification, dose-response assessment, expo- sure assessment, and risk characterization (NAS 1983). Risk assess- ment has also been used to describe the consequences of exposure to ETS. However, unlike many environmental exposures for which risk assessment represents the only approach for estimating human risk, the health effects of ETS exposure can be examined directly using epidemiological methods. Although this Report reviews several risk assessments done by individual researchers on ETS, its conclusions are based on the laboratory, toxicological, and epidemiological evidence. Extrapolation of Active Smoking Data to Environmental Tobacco Smoke Exposure Comparison of Mainstream Smoke and Sidestream Smoke A detailed comparison of mainstream and sidestream smoke can be found in Chapter 3. Mainstream smoke (MS) is the term applied to the complex mixture that is inhaled by the smoker from the mouthpiece of a cigarette, cigar, or pipe with each puff. Sidestream smoke (SS) is the aerosol that comes from the burning end of the cigarette, pipe, or cigar between puffs. Environmental tobacco smoke (ETS) is the term applied to the combination of SS and exhaled MS, which is diluted and aged in an area where smoking has taken place. Most of the existing data on mainstream and sidestream smoke characteristics relate to cigarette smoking and relatively little information is available pertaining to cigar and pipe smoking. Because both MS and SS are generated from the tip of the burning tobacco product, it is not surprising that their compositions are similar. Of the thousands of compounds identified in tobacco smoke, many have been identified as present in both MS and SS. Among these are carcinogens, gases such as carbon monoxide and the oxides of nitrogen, and nicotine. Since there is a wealth of information relating to the toxicity and carcinogenicity of MS, it should be emphasized again that ETS cannot be treated as a new environmen- tal agent for the purpose of assessing health risks. The presence of the same agents in MS and SS leads to the conclusion that ETS has a toxic and carcinogenic potential that would not be expected to be qualitatively different from that of MS. Quantitative differences between the active smoker’s exposure to MS and the involuntary smoker’s exposure to ETS are likely to be the more important 23 determinant of the differing magnitudes of risks associated with these two exposures. Differences in the composition of MS and SS primarily reflect their generation at different temperatures in different oxygen environments. Also, SS is diluted very rapidly, under most circum- stances, and has the opportunity to age before inhalation. The involuntary smoker usually inhales ETS, not SS, the aerosol that comes from the tip of a burning cigarette. In considering the characteristics of SS, it must be emphasized that much of the existing data about the composition of MS and SS is derived from studies carried out in special chambers rather than by sampling MS and SS generated by smokers. In these chamber studies, SS has been sampled by a probe located close to the burning tip. This experimen- tal situation clearly differs from that of a room with one or more smokers freely smoking. In that situation, SS is mixed with exhaled MS, diluted and aged. Nevertheless, these chamber studies provide very useful information about the compounds present in the SS. These studies have established that SS in comparison with MS has a higher pH, smaller particle size, and more carbon monoxide, benzene, toluene, acrolein, acetone, pyridine, ammonia, methyl- amine, nicotine, aniline, cadmium, radon daughters, benzo[a]pyrene and benzfajanthracene. Comparison of the relative concentrations of the various compo- nents of SS and MS smoke provides limited insights concerning the toxicological potential of ETS in comparison with active smoking. As described above, SS characteristics, as measured in a chamber, do not represent those of ETS, as inhaled by the nonsmoker under nonexperimental conditions. Further, the dose-response relation- ships between specific tobacco smoke components and specific diseases are not sufficiently established for the necessary extrapola- tions from active smoking to environmental tobacco smoke exposure for individual agents. For that reason the extrapolations in this section are confined to the dose-response relationships of whole smoke for those diseases with established dose-response relation- ships. With regard to the potential of ETS to cause lung cancer, undiluted SS has 20 to 100 times greater concentrations of highly carcinogenic volatile’ N-nitrosamines than MS (Brunnemann et al. 1978) as well as higher concentrations of benzopyrenes and benz[alanthracenes. For nonmalignant effects on airways and the lung parenchyma, the agents responsible for the development of acute and chronic respiratory disease have not been identified, although many tobacco smoke components have been shown to cause lung injury (US DHHS 1984). Presumably, both vapor phase (gaseous) and particulate phase (solid) components of MS are involved. Both airways disease and 24 parenchymal disease are probably a response to the total burden of respiratory insults, some of which, like active smoking, may be sufficient by themselves to cause physiologic impairment and ultimately, clinical disease. Others, such as ETS, may contribute to the total burden but be insufficient, individually, to cause clinical disease. Deposition of Mainstream Smoke and Sidestream Smoke and Environmental Tobacco Smoke Dose Estimates The dose of tobacco smoke delivered to the airways and alveoli depends, among other factors, on the volume of MS, SS, or ETS inhaled, on the rate and depth of inhalation, and on the size, shape, and density of the individual particles or droplets. Patterns of deposition of MS in the lungs have been described, but similar information about deposition patterns for ETS is not yet available. Without such data, it is necessary to extrapolate from the informa- tion on MS. The major factors that affect the pattern of deposition and retention for particles are particle size distribution and breathing pattern. The particle size range and mean aerodynamic diameter for particulates in sidestream smoke are similar to those of mainstream smoke (particle size range of 0.01 to 0.8 ym for sidestream smoke and 0.1 to 1.0 pm for mainstream smoke, and mean aerodynamic diameter 0.32 um for sidestream smoke and 0.4 pm for mainstream smoke) (see Chapters 3 and 4). The deposition site is determined largely by the size of the particles, with large particles being deposited preferentially in the nasopharynx and large conducting airways. Smaller particles are deposited more peripherally, and very small particles tend to be exhaled and to have a very low deposition fraction. The particulates of ETS, because of their size range, are likely to be deposited peripherally. The breathing patterns for the inhalation of MS and ETS are also different; MS is inhaled intermittently by the smoker with an intense inhalation, often followed by a breathhold that results in a more equal distribution. Environmental tobacco smoke, on the other hand, is inhaled continuously with tidal breaths when the passive smoker is at rest and with deeper inhalations when the passive smoker is physically active. Breathholding does not normally occur with tidal breathing. Estimates of the equivalent exposure, in terms of cigarettes per day, resulting from ETS, as compared with MS, vary quite widely and depend on the way in which the estimates were made. Repace and Lowrey (1985) estimated that nonsmokers in the United States are exposed to from 0 to 14 mg of tobacco tar (average 1.4 mg) per day.. Vutuc (1984) estimated that the exposure to environmental cigarette smoke is equivalent to 0.1 to 1 cigarette per day actively 25 smoked. Estimates of ETS exposure, based on cotinine measure- ments, suggest that involuntary smokers absorb about 0.5 to 1 percent of the nicotine that active smokers absorb (Jarvis et al. 1984; Haley and Hoffmann 1985; Wald et al. 1984; Russell et al. 1986). Dose-Response Relationships and Threshold for Risk Dose-response relationships for active smoking can provide in- sights into the expected magnitude of disease resulting from the exposure of nonsmokers to ETS. These data are reviewed to determine whether disease can be expected in association with ETS. Data from cohort and case-control studies demonstrate dose— response relationships for lung cancer, which extend to the lowest levels of reported active smoking. The dose-response relationship of active smoking with lung cancer risk has been described by several investigators in several different data sets (Whittemore and Altshu- ler 1976; Doll and Peto 1978; Pathak et al. 1986). Although the mathematical forms of these models vary, none have included a threshold level of active smoking that must be passed for lung cancer to develop. The dose-response relationship for active smoking and lung cancer has been used to project the lung cancer risk for nonsmokers (Vutuc 1984). Such projections yield risk estimates of 1.03 to 1.36 for exposures, considered to be reasonable estimates of involuntary smoking exposures, i.e., 0.1 to 1.0 cigarettes per day. The reference population for these risk estimates is the risk for nonsmokers as a group, including those with higher and those with lower exposures to environmental tobacco smoke. In contrast, the reference population for the risk estimates in studies of involuntary smoking is the lung cancer risk in only that group of nonsmokers who have lower exposure to ETS. Comparisons of lung cancer risk estimates from active smoking studies with those from involuntary smoking studies require reference to the same exposure group for proper interpreta- tion. In general, the lung cancer experience of all nonsmokers (ie., those with higher and lower involuntary smoking exposure com- bined) has been used to establish the reference rate of lung cancer occurrence (i.e., set as a risk of 1) in studies of active smoking. The use of all nonsmokers as the reference group averages the lower risks of nonsmokers with less ETS exposure with the higher risks of those with more ETS exposure. Thus, with the relative risk for the entire group of nonsmokers set to unity, the relative risk for nonsmokers with lower exposure is below 1 and that for the group with higher exposure is above 1. As a consequence, relative risk estimates from studies of involuntary exposure cannot be directly compared with risk estimates extrapolated from active smoking, unless comparison to a single level of exposure is possible. Failure to 26 consider the differences between the reference populations explains the apparent discrepancy noted by Vutuc. Consider, for example, the mortality study reported by Hirayama (1981a). In this study, the relative risk of lung cancer for nonsmoking wives of smoking husbands (current and former) compared with nonsmoking wives of nonsmoking husbands (as calculated from Figure 1 in Hirayama 198la) was 1.78. If the relative risk for nonsmoking wives of nonsmoking husbands were expressed in relation to the combined group of nonsmoking women, then a value of 0.63 is obtained, while with a similar calculation, that for nonsmoking wives of smoking husbands (both current and former), yields a value of 1.12. Thus, when the appropriate comparison is made, the risk estimates developed by extrapolation of the active smoking data (1.03 to 1.36) closely approximate those actually found in a study of lung cancer risk due to involuntary smoking. Dose-response relationships between active smoking and the level of lung function, the rate of decline of lung function in adult life, and the development of chronic airflow obstruction are well established (US DHHS 1984). Different measures of dose have provided the strongest correlation with functional decline in different studies. Pack-years, a cumulative dose measure, was the strongest predictor of the level of forced expiratory volume in 1 second (FEV)) in the Tucson epidemiologic study (Burrows, Knudson, Cline et al. 1977). Duration of smoking and the amount smoked were found to be the best predictors in male subjects in a study of three U.S. communities (Beck et al. 1981), and pack-years was the best predictor in female subjects. In both of these studies, however, the estimated dose accounted for only about 15 percent of the variation of age- and height-adjusted FEV: levels. The relatively low predictive capability of cigarette smoking variables in these studies most likely reflects a lack of information on the determinants of individual susceptibility to tobacco smoke. Further, exposure variables obtained by question- naire, such as the number of cigarettes smoked daily, may only roughly approximate the dose delivered to target sites in the respiratory tract. Many factors, such as puff volume, lung volume at which inhalation starts, and airways geometry will influence the smoke dose and its distribution within the lungs. Extrapolation from the results of these studies to the pulmonary effects of exposure to ETS is, therefore, likely to be inaccurate. Another approach for assessing low-dose exposures is to consider the information available from studies involving children and teenagers who have recently taken up smoking. Even with brief smoking experience, cross-sectional studies of active cigarette smok- ing by children and adolescents have demonstrated an increased frequency of respiratory symptoms (Rawbone et al. 1978; Rush 1974; Bewley et al. 1973; Seely et al. 1971) and small but statistically 27 significant reductions in lung function (Seely et al. 1971; Peters and Ferris 1967; Lim 1973; Walter et al. 1974; Backhouse 1975; Woolcock et al. 1984). Longitudinal studies involving children and adolescents have demonstrated that a physiologic impairment attributable to smoking may be found in some children by age 14 and may be present after only 1 year of smoking 10 or more cigarettes per week in children with previously normal airways (Woolcock et al. 1984), and that relatively small amounts of cigarette use may lead to significant effects on FEV: and on the growth of lung function in adolescents (Figure 1) (Tager et al. 1985). When considering the risk of low-dose exposures for the develop- ment of chronic respiratory disease, the existence of a spectrum of risk and a distribution of dose within the population should be taken into consideration. The characteristics of the part of the population most susceptible to involuntary smoke exposure is still being clarified. Evidence is accumulating that airways hyperrespon- siveness, atopy, childhood respiratory illness, and occupational exposures may all influence response to ETS. Current understanding of lung injury suggests that individuals with one or more of these characteristics that place them at the most sensitive end of the susceptibility curve may be the most likely to develop symptoms or functional changes as a result of ETS exposure. Dose of ETS also varies in the population, and the coincidence of high dose and increased susceptibility may convey a particularly high risk. Fur- thermore, ETS exposure may damage lungs that are also affected by other insults. Pathophysiologic Considerations Cancer Carcinogenesis refers to the process by which a normal cell is transformed into a malignant cell with uncontrolled replication. Carcinogenesis has been conceptualized as a multistage process involving a sequence of alterations in cellular DNA that terminate with the development of a malignant cell. Agents acting early in this sequence are referred to as initiators; those acting later are referred to as promoters. Compounds with both initiating activity and promoting activity have been identified in tobacco smoke. Carcinogenesis reflects DNA damage; although some repair may take place, biological models have not suggested that there is a threshold of damage that must be exceeded. Rather, carcinogenesis has been considered to involve a series of changes, each occurring at a rate dependent on the dose of a damaging agent. Higher doses increase the probability that the entire sequence will be completed, but lower doses may also lead to malignancy. 28 140 3 > A ¢ ¢ + a . < 120 - w sad + ; ~ oat + + + 100 4, ¢ . +o4 a yy . ° 5 > +> S + a 80 4 cd > : . . 60 +4 + 7 7 v ¥ Tv ¥ 7 y ¥ 0 10,000 20,000 30,000 40,000 50,000 60,000 70,000 + —-80,000 Number of cigarettes consumed 150 + 8 > a 125 4 . + pe fh fh. + ° wi + + w wWO7e% 3 *- + . + + + + + + & 754 + + 3 .* + é 50 - + Sd 25 + tT T ¥ rt T T F T T 0 10,000 20,000 30,000 40,000 50,000 60,000 (70,000 80,000 Number of cigarettes consumed FIGURE 1.—Relationship between levels of predicted for FEV, (A) and FEF z-z (B) at examination 8 and cumulative number of cigarettes smoked during examinations 4 through 8 NOTE: Men and women combined (N= 44). SOURCE: Tager et al. (1985). with the PiZZ or other phenotypes, are modest particulate exposures likely to increase the risk for disease to an appreciable extent. The development of acute and chronic airway disease or symptoms of cough, phlegm production, and wheeze may require a considerably smaller exposure than changes in the lung parenchyma, and it is not unreasonable to hypothesize that these symptoms may be related to repeated and continuous exposure to ETS in the susceptible individu- al. Strong evidence that low-dose active smoking causes increased rates of respiratory symptoms and functional impairment comes from the studies of children and adolescents discussed earlier (Woolcock et al. 1984; Tager et al. 1985). Because of the length of exposure, it is likely that these reflect airway rather than parenchy- mal effects. Another pathophysiological mechanism by which exposure to ETS may increase an individual’s risk for the development of chronic airflow obstruction is through respiratory viral infections. Mounting evidence indicates that the very young child (under 2 years of age) exposed to ETS is at increased risk for lower respiratory tract viral infections (Harlap and Davies 1974; Colley 1974; Colley et al. 1974; Leeder et al. 1976a; Fergusson et al. 1981; Dutau et al. 1979; Pedreira et al. 1985). There is also increasing, though still inconclusive, epidemiologic evidence that respiratory viral infections in early life may be associated with an accelerated decline in FEV: and, therefore, an increased risk for the development of chronic airflow obstruction in adult life in smokers (Burrows, Knudson, Lebowitz 1977; Samet et al. 1983). By increasing the occurrence of viral infections of the lower respiratory tract in early life, exposure to ETS in childhood may have an appreciable, but indirect, effect on the risk for the development of chronic airflow obstruction in adult life. The structural basis for this increased susceptibility has not yet been elucidated, however. Furthermore, the child whose parents smoke is also more likely to take up smoking than is the child of nonsmoking parents. Thus, the child made susceptible to the effects of active smoking by prior ETS exposure is also more likely to become an active smoker. The possibility that exposure to constituents of tobacco smoke in utero may exert a prenatal effect must also be considered. This exposure is clearly not the same as ETS exposure, since the lungs of the fetus are not being exposed to ETS; rather, the developing fetal lung is exposed to compounds absorbed by the mother and delivered to the fetus transplacentally. Evidence of an in utero effect in pregnant rats has been reported by Collins and coworkers (1985). These investigators reported that pregnant rats exposed to smoke from day 5 to day 20 of gestation, in comparison with control rats, showed reduced lung volume at term and saccules that were reduced in number and increased in size as a result of the reduced formation 31 Lung Disease The noncarcinogenic pathophysiologic effects of active smoking on the respiratory tract can be separated into (1) effects on the airways and (2) effects on the lung parenchyma. In the airways, the structural changes include inflammation in the small airways and mucous gland hypertrophy and hyperplasia. In the parenchyma, the main structural change is alveolar wall destruction. Both the airways and the parenchymal changes are caused by active smoking, but the interrelationships of these changes are not clear. They may be independent pathophysiologic processes, linked only by their joint association with tobacco smoking. As discussed earlier, there is evidence showing an approximately linear dose-response relationship between FEV; level and amount smoked; however, the dose-response relationships have not been as well described for the underlying pathophysiologic changes in the airways or in the lung parenchyma. Host factors and other environ- mental factors presumably interact with active smoking to affect an individual’s risk for the development of disease. In this regard, present evidence would suggest that only 10 to 15 percent of smokers develop clinically significant airflow obstruction, although parenchy- mal and airways changes can be demonstrated in a substantially higher percentage at autopsy (US DHHS 1984). Extrapolation from the evidence on active smoking to the likely effect of exposure to environmental tobacco smoke on the airways and parenchyma suggests that pathophysiologic effects on both the airways and the lung parenchyma might be expected. Because the dose of smoke components from ETS exposure is small in comparison with the dose from active smoking, the extent of lung injury would most likely also be much smaller than that found in active smokers. Small changes in the lung may be below the threshold for detection on pulmonary function testing. If clinically significant chronic airflow obstruction occurs in nonsmokers exposed to ETS, the risk is likely to be concentrated among those individuals highly susceptible to the airway or parenchymal effects of cigarette smoke. This susceptible group may include individuals with bronchial hyperre- sponsiveness and with other, as yet unidentified, genetic and familial risk factors. Identifying the risk factors for susceptibility to the airway and parenchymal effects of both mainstream smoke and ETS is an important priority. The dose of environmental tobacco smoke received by the nonsmoker is unlikely, by itself, to be sufficient to cause a clinically significant degree of parenchymal disease (em- physema) unless an individual is at the extreme end of the susceptibility distribution. Any particulate load is likely to increase the elastase burden in the lungs by causing an influx of neutrophils. However, only in the individual with very inadequate lung defenses, specifically severe deficiency of protease inhibitor (Pi) associated 30 of saccule partitions. These hypoplastic lungs showed an internal surface area that was decreased. Whether this study in rats has any relevance to humans is not yet clear, but this issue deserves further investigation. Whether continued exposure to ETS during childhood, while the lung is remodeling and growing, affects the process of growth and remodeling is not yet clear. In general, rapidly dividing cells and immature organs are more susceptible to the effects of environmen- tal toxins than are cells undergoing a normal rate of division and mature organs. Apart from the evidence, cited above, linking lower respiratory tract viral infections in very early life to an accelerated decline of FEV: in adult life, there is no information yet to link the rate of growth of lung function during childhood to the rate of decline of lung function in adult life because the necessary longitudi- nal studies have not been done. More information is needed to describe the relationship of exposure to ETS at various times during childhood to the maximal level of lung function achieved at full lung growth. Methodological Considerations in Epidemiologic Studies Measurement of Exposure In assessing the health effects of ETS exposure, as with other environmental pollutants, accurate assessment of exposure is critical for obtaining estimates of this agent’s effects. Both random and systematic misclassification of the exposures of subjects in an investigation are of concern. Random misclassification refers to errors that occur at random; the consequence of such random misclassification is to bias toward finding no effect. Systematic misclassification refers to nonrandom errors in exposure assessment, the consequence may be to bias toward a greater or lesser effect than is actually present. Biased answers in response to a questionnaire may introduce systematic misclassification. Some misclassification occurs in most observational (nonexperi- mental) epidemiological studies, and is inherent in all epidemiologi- cal studies of ETS. Tobacco smoking is ubiquitous in nearly all environments; few people escape being exposed to ETS. Thus, the exposure variables for ETS in epidemiological studies do not separate nonexposed subjects from exposed subjects; rather, they identify groups with more or less exposure, or with a qualitative or semiquantitative gradient of exposure. In assessing exposure to ETS, the information should cover the biologically appropriate time period for the health effect of interest and be collected in a form that permits the construction of biologically appropriate exposure measures. However, the collection of a full lifetime history of ETS exposure, as in a study of malignancy, may not be feasible, and the accuracy of the informa- 32 tion may be limited. In evaluating the effects of ETS exposure, cumulative exposure, duration of exposure, and intensity of exposure may each influence the magnitude of effects, as may the timing of exposure in relation to age and level of development. Because of the difficulties inherent in assessing exposures through questionnaires, increased emphasis has been placed on measuring exposure through the use of molecular or biochemical markers. With available markers, this approach is limited to providing an indica- tion of recent (within 48 hours) exposure, which may not necessarily correlate with past exposure. A marker has not yet been devised for total integrated dose. Nevertheless, biological markers provide another method for classification of current exposure, and a stan- dard for validating questionnaires. The strengths and weaknesses of the existing methods of measur- ing exposure are further discussed below. Atmospheric Markers A number of different markers of atmospheric contamination by tobacco combustion products can be feasibly measured. Ideally, the atmospheric levels of the air contaminant or class of contaminants that are implicated in producing the adverse health effects would be measured. A variety of contaminants have been measured as indicators of ETS, but no single measure can adequately index all of its myriad components. Further, some contaminants are produced by sources of environmental contamination other than tobacco smoke. Nicotine is absorbed only from tobacco and tobacco combustion products. Some of the pollutants that have been measured include (1) carbon monoxide, (2) respirable suspended particulates (RSP), (3) nicotine, (4) a number of aromatic hydrocarbons, such as benzene, toluene, benzo-pyrene, and phenols, and (5) acrolein. Some of these are in the vapor phase and some in the particulate phase. Some, such as nicotine, may exist in one phase (particulate) in MS and in the other (gas) phase in SS. Until more is learned about the contaminants and their physical state in ETS, the results of monitoring for a particular ETS component will be difficult to relate to its disease-causing potential. At a practical level, the technology for measuring nicotine levels and RSP levels is available and accurate. Personal Monitoring Both active and passive personal monitors can be used to measure an individual’s total exposure to an air contaminant at the breathing zone. Active personal monitoring systems employ pumps to concen- trate the air contaminants on a collection medium for laboratory analysis or to deliver the air to a continuous monitor. Passive 33 personal monitoring systems use diffusion and permeation to concentrate gases on a collection medium for laboratory analysis. Personal monitoring should provide a more accurate estimate of the dose of a contaminant than area monitoring, because the actual air in the breathing zone is sampled and the subject’s time-activity pattern is inherently considered. As with area monitoring, the results for a particular component of ETS may not adequately characterize exposure to other components responsible for a particular disease or effect. Respirable suspended particulates can be measured with accuracy and give a reasonably accurate measurement of current exposure. ‘ Questionnaires The questionnaire has been the most frequently used means of estimating exposures for epidemiological investigations. Question- naires typically have obtained information about the smoking habits of parents, spouses, or other family members and often about exposure outside the home. From this information, the subject is classified as exposed or not exposed to ETS, and the extent of exposure may be estimated. The questionnaire approach for exposure estimation has several potential limitations. First, the information obtained cannot exhaus- tively cover lifetime exposure to ETS; therefore, a completely accurate reconstruction of integrated dose over the years cannot be achieved. Second, in evaluating ETS exposure in the home, the usual daily smoking of the smokers has often been used as a measure of exposure intensity at home. This assumption may not be correct, since smoking does not occur only in the home. For example, a one- pack-a-day smoker may smoke only five cigarettes a day in the home environment and smoke the rest at work or elsewhere outside the home. Third, quantitation of exposure in the workplace is inherently difficult because of changes in jobs and the varying exposure in any particular workplace. Despite these shortcomings, the information obtained by question- ‘aires does discriminate between more exposed and less exposed ubjects. The evidence validating the questionnaire method is trongest for domestic exposure. In several studies, levels of cotinine in body fluids have varied with reported exposure to tobacco smoke at home (Greenberg et al. 1984; Wald and Ritchie 1984; Matsukura et al. 1984; Jarvis et al. 1984). In fact, residence with a smoker may identify a population that is more tolerant of ETS, and therefore more likely to be exposed outside the home. Evidence in support of this speculation is provided by a study of urinary cotinine levels in nonsmoking men in the United Kingdom (Wald and Ritchie 1984). In this study, the men married to women who smoked reported a 34 greater duration of exposure outside the home than men married to women who did not smoke. Until accurate and inexpensive exposure markers are available for cumulative ETS exposure, the questionnaire approach will remain the simplest means of obtaining exposure information. It is, there- fore, important to consider the misclassification that can be intro- duced by using this indirect measure of exposure. In studies of the effect of ETS exposure, two types of misclassification are of concern: misclassification of current or former smokers as never smokers and misclassification of the extent of ETS exposure. Because active smoking has a greater effect on the lungs than exposure to ETS, the inclusion of active smokers within a larger group of nonsmokers may lead to the finding of a significant effect on lung function, which is actually attributable to active smoking rather than to involuntary smoking. Misclassification of undeclared active smoking is a particularly important source of error in studies involving teenagers. Misclassification of smoking status is also of concern in case-control studies of the association between exposure to ETS and lung cancer. Information about smoking habits for these studies often comes from interviews with a surviving spouse or surrogate, who may have been a close family member, neighbor, or friend, or from a review of medical records. The smoking habits of the subject may be incorrectly reported. Classification of individuals who are current or former smokers as never smokers would lead to a spurious increase in the relative risk for lung cancer in nonsmokers exposed to ETS, because the smoking habits of spouses tend to be correlated. The extent of this bias in the case-control studies is uncertain. The proportion of people reported as never smokers, but who in fact did smoke in the past, is unknown. The proportion of current smokers who report themselves as nonsmokers can be estimated from studies using markers to validate questionnaires. Using biochemical markers of tobacco smoke absorption, the propor- tion would appear to be about 0.5 to 3 percent, depending on the population studied and the questionnaire used (Wald et al. 1981; Saloojee et al. 1982). Misclassification of the extent of ETS exposure can also occur, and may reduce the observed risk if a nonsmoking spouse of a smoker is not exposed to smoke at home. Friedman and colleagues (1983), reporting on a survey of 38,000 subjects, noted that 47 percent of nonsmoking women married to smokers reported that they were not exposed to tobacco smoke at home. Measurements of Absorption The difficulties inherent in estimating exposure and dose have provided the impetus for the development of biological markers for exposure to both MS and ETS. The marker that at present holds the 35 highest promise is cotinine, the major metabolite of nicotine. Cotinine may be measured in saliva, blood, or urine. Numerous studies have demonstrated that there is good correlation between these measures of cotinine and the estimated exposure to tobacco smoke under laboratory conditions (Russell and Feyerabend 1975; Hoffmann et al. 1984) and under conditions of daily life (Russell and Feyerabend 1975; Feyerabend et al. 1982; Foliart et al. 1983; Wald et al. 1984; Wald and Ritchie 1984; Jarvis et al. 1984; Matsukura et al. 1984; Greenberg et al. 1984). Cotinine is probably the best marker for tobacco smoke intake because it is highly sensitive and specific for tobacco smoke and because it can be detected both in active smokers and in individuals exposed to ETS. Further details about cotinine and other markers are to be found in Chapter 4. Potentially Confounding Variables In any epidemiological study, the confounding factors must be considered and their effects controlled. Confounding refers to the biasing effect of a factor that independently influences the risk for the disease of concern and is also associated with the exposure under evaluation. Confounding is of particular concern when the effects of the exposure of interest are expected to be small. The potential confounding variables depend on the health outcome of interest. For lung cancer, occupational exposures, diet, and exposure to other combustion products are of concern. For acute and chronic pulmonary effects, potential confounders include airways hyperresponsiveness, other indoor air pollutants, outdoor air pollu- tion, respiratory tract infections, occupational exposure, and socio- economic status, which may potentially influence disease risk through its environmental correlates. While this list is extensive, it may not be inclusive; in any single investigation it may not be to measure and control all potentially confounding vari- es. Statistical Issues In general, the evidence on active smoking in combination with the dosimetry of involuntary smoking leads to the conclusion that the effects of ETS on a population will be substantially less than the effects of active smoking. The effects of ETS on infants and young children are an important exception. The association of ETS with an adverse effect in an individual study may reflect bias, chance, or a causal relationship. Statistical significance testing is used to quantitate the role of chance; by convention, a p (probability) value less than 0.05 is deemed statisti- truly no association between ETS and the effect. The choice of 0.05 is arbitrary, and as the significance level declines, the probability that the observation could have occurred by chance lessens. For effects of small magnitude, as may be anticipated for some consequences of exposure to ETS, a large study population may be necessary to demonstrate statistical significance. The absence of statistical significance for an association may reflect an inadequate sample size and is not always indicative of the absence of an association. In this regard, reports describing the absence of effects of ETS should provide the calculations needed to demonstrate the study’s statistical power (ability to detect effects of the magnitude expected) or a confidence interval for the estimate of effect. An additional statistical issue is the directionality of statistical significance testing. Either one-sided or two-sided tests may be used; in the first, only effects in one direction are considered a possibility, whereas two-sided tests consider the Possibility of effects in opposing directions, i.e., increase or decrease of risk. Given the strength of the evidence on active smoking and disease risk, one-sided testing in the direction of an adverse effect seems appropriate for most potential consequences of ETS. However, one-sided tests have not been performed in all investigations of ETS; the use of two-sided tests makes these studies conservative, as statistical significance will less often be attained. Respiratory System Effects of Involuntary Cigarette Smoke Exposure This section reviews the evidence on involuntary smoking and the adverse physiologic effects, respiratory symptoms, and respiratory diseases in nonsmoking adults and children. Health effects related to fetal exposure in utero from active smoking by the mother are not discussed. Lung growth and development may be influenced by in utero exposure, and the effects of such exposures have not been separated from those of exposure after birth. More complete treatments of this issue have been published (US DHEW 1979; US DHHS 1980; Abel 1980; Weinberger and Weiss 1981). This section begins with a review of the data on infants and children who are exposed primarily through parental smoking. The health effects examined are increased respiratory illnesses, of both the upper and the lower respiratory tracts, increased chronic respiratory symptoms and illnesses, and alterations in lung growth and development. Studies of adults, whose exposures to environmen- tal tobacco smoke occur in a variety of settings, are examined with regard to symptoms and changes in measures of lung function. The potential for ETS to produce bronchoconstriction in asthmatic and nonasthmatic subjects is also examined. 37 Infants and Children Acute Respiratory Illness Longitudinal Studies A number of studies, based on a variety of different designs, have examined the effects of involuntary smoking on the acute respira- tory illness experience of children (Table 1). Several different end points have been evaluated in these investigations: hospitalization for bronchitis or pneumonia as asseased by hospital records (Harlap and Davies 1974; Rantakallio 1978); questionnaire assessment of hospitalization for bronchitis or pneumonia or of doctor’s visits (Colley 1971; Leeder et al. 1976a) or both (Fergusson et al. 1981; Fergusson and Horwood 1985); questionnaire assessment of respira- tory illness within the last year (Cameron et al. 1969; Schenker et al. 1983; Ware et al. 1984); chest illness before age 2 (Schenker et al. 1983); hospitalization for respiratory syncytial virus (RSV) infection (Sims et al. 1978; Pullan and Hey 1982); physician-diagnosed bronchitis, tracheitis, or laryngitis (Pedreira et al. 1985); and tonsillectomy as an indication of recurrent respiratory infection (Said et al. 1978). These diverse end points range from illnesses associated with a specific etiologic agent, e.g., RSV bronchiolitis, to clinician-diagnosed syndromes, e.g., bronchitis of undetermined etiology. The possibility of reporting bias must be considered for the studies that have used questionnaires to measure illness experience. In most of these studies, parents, usually the mother, have responded for the child and reported on the child’s illness experience. Some investiga- tors have suggested that mothers with respiratory symptoms are more likely to report symptoms for their children and that stratifica- tion of subjects by the symptom status of their parents removes this element of recall bias (Lebowitz and Burrows 1976). Removal of symptomatic parents, however, may result in overcorrection for recall bias because cigarette smoking is associated with symptoms in the adult. This analytical strategy would not be expected to adjust for biased parental recall of early life events. Additionally, in all studies in which potential reporting bias was examined, control for parents’ status reduced, but did not eliminate, associations of involuntary smoking with health outcomes (Colley et al. 1974; Leeder et al. 1976a,b; Schenker et al. 1983; Ware et al. 1984). Further, the consistency of these studies, in spite of differing study populations and methods, weighs against bias as the sole explanation for the effect of involuntary smoke exposure. Harlap and Davies (1974) studied 10,672 births in Israel between 1965 and 1968 and observed that infants, whose mothers, at a prenatal visit, reported that they smoked, had a 27.5 percent greater hospital admission rate for pneumonia and bronchitis than children 38 TABLE 1.—Early childhood respiratory illness and involuntary cigarette smoking Study Subjects Findings Tilness rates per 100 Comments By cigarettes per day 0 1-10 11-20 2+ Harlap and Davies 10,672 births, 1965-1968, Hospitalized, bronchitis/ 95 10.8 16.2 31,7 Prenatal smoking history; (1974) Israel pneumonia, first year of life maternal smoking only RR=1.38 Longitudinal study Colley' 2,205 births, 1963-1965, Questionnaire, bronchitis/ 18 10.4 M1 15.2 == Asymptomatic parents (1971) England pneumonia, first year of life 10.3 16.1 145 B2 = Symptomatic parents RR=1.78 for one parent smoker Neither controlled for sibling RR=2.60 for two parent smokers number or smoker sex : Longitudinal study Fergusson et al. (1981), 1,265 births, 4 months, Questionnaire, doctor or hospital 1.0 128 19.4 Maternal Effect significant for maternal Fergusson and Horwood 1977, New Zealand visits, bronchitis/pneumonia; only amoking in first year of life (1985) hospital records checked; assessed 7.0 48 88 Paternal only; effect present in first 2 at 4 months, 1, 2, 3, and 6 years; only years of life RR=2.04 if mother smoked By number of smoking parents 0 1 2 ~~ Ware et al. 8,528 children, aged 5-9, Respiratory illness in last year 12.9 18.7 148 Adjusted for age, sex, and city (1984) with two parents’ smoking cohort effect; significant trends status known, six U.S. Longitudinal study cities TABLE 1.—Continued Study Subjects Findings Tiness rates per 100 Comments Said et al. 3,920 children, aged 10-20, Tonsillectomy and/or 28.2 M14 50.9 Children self-reported; not clear (1978) France adenoidectomy, generally before parent smoking habit at report age 5, as indicator of frequent time directly related to Tespiratory tract infection exposure approx. 10+ years earlier O tional study Schenker et al. 4,071 children, aged 5-14, Chest illness before age 2 6.7 79 115 Trends for both significant (1983) United States Cheet illness >3 days in past 88 11.8 13.6 Cross-sectional study year Parent status Nonsmoker Current smoker Cameron et al. 158 children, aged 6-9; Respiratory illness, reatricted 1,33 14 Tineas reported not verified; (1969) parents’ telephone activity and/or medical not clear how reporting adult questionnaire, United States consultation in last year related to child Cross-sectional study Leeder et al. 2,149 infants, born 1963- RR ~ 2.0 for infante with two Not provided Parente’ response bias unlikely, (1976a, b) 1965, England amoking parents effects observed for infants of asymptomatic parents; maternal vs. paternal smoking effects not investigated Longitudinal study Sims et al. 365 children, hospitalized, Borderline significant increase in Not provided No significant effect for (1978) RSV bronchiolitis; 35 maternal smoking, firet year of paternal smoking; average controls, England life amount amoked greater for RR=2.65 parents of cases than controls Case-control study lt TABLE 1.—Continued Study Subjects Findings Tlineas rates per 100 Comments \ Rantakallio 1,821 children of smoking Significant increase in Not provided Prospective followup of doctor (1978) mothers, hospitalization for respiratory visita, hospitalizations, deaths 1,823 children of illness during first 5 years of life up to age 5; only maternal nonsmoking mothers, RR=1.74 smoking evaluated Finland Longitudinal study Pullan and Hey 190 children hospitalized, Significant effect of maternal Not provided Case-control study (1982) RSV infection, first year of (RR=1.96) and paternal (RR=1.53) life; 111 nonhospitalized smoking at time of study; controls, England significant maternal smoking effect during first year of life (RR=1.55) Nonsmoker Smoker Pedreira et al. 1,144 infants in pediatric Significant increase in respiratory Bronchitis 71 103 Pediatricians not blinded to (1985) practice, United States illnesses among smoke-exposed Tracheitis 21 4 exposure; no effect seen for children Laryngitis 4 7 croup, pneumonia, or bronchiolitis Longitudinal study >» These data are considered in a more expanded analysis provided by Leeder et al. (1976a, b). * Relative risk for children of smoking mothers versus child of king mothers d from data provided by J.M. Samet (personal communication). of nonsmoking mothers. In addition, they demonstrated a dose- response relationship between the amount of maternal smoking and the number of hospital admissions for these conditions. The infants were classified by the mothers’ prenatal smoking behavior and not by the mothers’ smoking behavior during the first year of the child’s life. Maternal smoking habits would probably have remained relatively stable across the short observation period. British. investigators (Colley et al. 1974) followed children born between 1963 and 1965 in London and also observed an increased frequency of bronchitis and pneumonia during the first year of life in the children of parents who smoked. This difference did not persist at 2 to 5 years of age. This effect was independent of the parents’ personal reports of winter morning phlegm and increased with the amount of smoking by parents. The annual incidence of bronchitis and pneumonia during the first year of life also increased with a greater number of siblings. This variable was not controlled in the original analysis; however, Leeder and colleagues (1976b) subse- quently reported that, in this same cohort, a dose-response relation- ship with parental smoking persisted for bronchitis and pneumonia in the first year of life, after control for parental respiratory symptoms, the sex of the child, the number of siblings, and a history of respiratory illness in the siblings. Fergusson and colleagues (1981) studied 1,265 New Zealand children from birth to age 3. They demonstrated an increase in bronchitis and pneumonia and in lower respiratory illness during the first 2 years of life in children whose mothers smoked compared with children whose mothers did not smoke. Correction for maternal age, family size, and socioeconomic status did not affect the relationship between the amount of maternal smoking and the rate of respiratory illness. The effect of maternal smoking declined with increasing age of the child. In a second report (Fergusson and Horwood 1985) the followup was extended to include the first 6 years of life. The results confirmed the initial findings. Maternal, but not paternal, smoking was associated with a statistically significant increase in lower respiratory illnesses during the first 2 years of life. However, after age 2 there was no significant effect of maternal smoking on respiratory illness occur- rence. Rantakallio (1978) followed more than 3,600 children during the first 5 years of life; half of the children had mothers who smoked cigarettes during pregnancy and half did not. The children of mothers who smoked had a 70 percent greater chance of hospitaliza- tion for a respiratory illness than the children of nonsmoking mothers. Pedreira and associates (1985) prospectively studied 1,144 infants and their families in the greater Washington, D.C., area. Maternal 42 smoking was associated with an excess frequency of acute bronchitis, tracheitis, and laryngitis, as diagnosed by the pediatricians caring for these families. Episodes of croup, pneumonia, and bronchiolitis were not increased by maternal smoking. A family history of chronic anna symptoms was also associated with excess respiratory ess. Ware and coworkers (1984) studied more than 10,000 children in six American cities. Maternal cigarette smoking was associated with increased parental reporting of a doctor-diagnosed respiratory illness before the age of 2 years and of an acute respiratory illness within the past year. The prevalence of positive questionnaire responses increased consistently with the current daily cigarette consumption of the mother; the dose-response relationships were unchanged by adjustment for maternal symptoms and educational status. Cross-Sectional Studies Schenker and coworkers (1983) studied 4,071 children between the ages of 5 and 14 years in a cross-sectional study in Pennsylvania. Both chest illness in the past year and severe chest illness before age 2 were more frequently reported in nonsmoking children of parents who smoked. These investigators found that symptom and illness rates were higher in children of parents with respiratory symptoms. However, a significant effect of maternal smoking on these illness variables remained after adjustment for the parents’ own respira- tory symptom history. In a study of 1,355 children between 6 and 12 years of age in the Iowa public schools, Ekwo and coworkers (1983) found that the presence in the home of at least one parent who smoked was significantly associated with reported hospitalization of the child for a respiratory illness during the first 2 years of life. As in other studies, the effect was stronger for maternal smoking than for paternal smoking. Case-Control Studies In England, Sims and colleagues (1978) examined 35 children at 8 years of age who had been hospitalized during infancy for RSV bronchiolitis and compared them with 35 control children of similar age. Maternal smoking was associated with a relative risk of 2.65 for hospitalization due to bronchiolitis. The sample size was small, and this effect of maternal smoking was not statistically significant. Pullan and Hey (1982) studied children who had been hospitalized with documented RSV infection in infancy. They found significantly greater smoking by their mothers at the time of the infection, compared with children hospitalized for other illnesses, including respiratory disease for which RSV infection was not documented. At 43 age 10, the children previously ill with RSV infection had an excess reported occurrence of wheeze and asthma and had lower levels of pulmonary function in comparison with the controls. The research- ers could not determine whether the RSV infection had caused persistent damage that affected the maturation of the lung or - whether these children were already more susceptible to severe RSV infection because of pulmonary problems that antedated the RSV infection. In summary, the results of these studies show excess acute respiratory illness in the children of parents who smoke, particularly in children under 2 years of age. This pattern is evident in studies conducted with different methodologies and in different locales. The increased risk of hospitalization for severe bronchitis or pneumonia associated with parental smoking ranges from 20 to 40 percent during the first year of life. Young children appear to represent a more susceptible population for the adverse effects of involuntary smoking than older children or adults. The time-activity patterns of infants, which generally place them in proximity to their mothers, may lead to particularly high exposures to environmental tobacco smoke if the mother smokes. Acute respiratory illnesses during childhood may have long-term effects on lung growth and development, and might increase the susceptibility of the lung to the effects of active smoking and to the development of chronic obstructive lung disease (Samet et al. 1983; US DHHS 1984). Cough, Phlegm, and Wheezing - Anumber of cross-sectional studies from different countries (Table 2) have shown a positive association between parental cigarette smoking and the prevalence of chronic cough and chronic phlegm in children; some studies have shown a relationship for persistent wheeze. However, not all studies have shown a positive relationship for all symptoms. The results of some of these studies may have been confounded by the child’s own smoking habits (Colley et al. 1974; Bland et al. 1978; Kasuga et al. 1979). The association with parental smoking was not statistically significant for all symptoms in all studies (Lebowitz and Burrows 1976; Schilling et al. 1977; Schenker et al. 1983). However, the majority of studies showed an increase in symptom prevalence with an increase in the number of smoking parents in the home. A recent report (Charlton 1984) provides cross-sectional data on parent-reported cough for 15,000 children, 8 to 19 years of age, in northern England. Chronic cough in the children was related to their age and to their own cigarette smoking status. However, with control of these factors by stratification, the number of parental smokers in the home was positively associated with the occurrence of chronic 44 TABLE 2.—Chronic respiratory symptoms in children in relation to involuntary smoke exposure Study Subjects Rates per 100 by number of smoking parents Respiratory symptoms or illness 0 Comments Colley et al. (1974) 2,426 children, aged 6-14, England Chronic cough; questionnaire 15.6 completed by parent Trend significant; reporting bias - possible reeult of parent symptoms or active smoking in children, unlikely to explain full effect of trend Crose-sectional study Bland et al. (1978) 3,105 children, aged 12-13, did not admit te ever smoking cigarettes, England Children’s self-reported symptoms and smoking history collected simultaneously; morning and daytime cough suggested as different diseases, could be difference in exposure (exposure more likely awake than asleep) Crogs-sectional study, adjusted for child’s own smoking habits Weiss et al. (1980) 650 children, aged 5-9, United States Trend not significant Trend significant Cross-sectional study, adjusted for parental symptoms and child’s own smoking . Charlton (1984) 15,000 children, aged 8-19 years, England Cough during day or at night 16.4 Morning cough 15 Chronic cough and phlegm L7 Persistent wheeze 18 Any cough 40.0 Trend significant; percents not age adjusted Cross-sectional study, adjusted for child’s own smoking, not parental symptoms 9F TABLE 2.—Continued Rates per 100 by number of smoking parents aataneecan Rc Study Subjects Respiratory symptoms or illness 0 1 2 Comments Dodge 628 children, grades 3-4, Any wheeze 27.6 27.9 40.0 All trends significant; some effect (1982) two-parent households; might relate to parental symptoms, parent questionnaire Phlegm 6.4 10.9 12.0 but no trend influence likely response, United States Cross-sectional study Cough 14.6 23.0 27.8 Schenker et al. 4,071 children, aged 5-14, Chronic cough 6.2 1.0 8.3 Trend not significant; not adjusted (1983) United States for parental symptoms, although Chronic phlegm 4.1 48 4.0 parental symptom effect analyzed Cross-sectional study Persistent wheeze 1.2 11 5.4 Never Parent smoker smoker Lebowitz and 1,525 children, <15 years Persistent cough 3.7 1.2 Higher rates in symptomatic Burrows old, United States parent households; trends persisted (1976) Persistent phlegm 10.0 12.8 for asymptomatic households; no adjustment for child’s own smoking Wheeze 23.4 24.1 Cross-sectional study Schilling et al. 816 children, age 7+, Cough, phlegm, wheeze No significant effect Specific data not provided (1977) United States Cross-sectional study Kasuga et al. 1,937 children, aged 6-11, Wheeze, asthma Increased prevalence in Adjusted for distance of home from (1979) Japan heavy smoker (>21 cig/day) main traffic, highway family; less clear effect in Crogs-sectional study light smoker (<21 cig/day) family Ekwo et al. 1,355 children, aged 6-12, Coughs with colds Odds ratios: 1.4 for smoker Gas stove use measured, not (1983) United States father, 1.5 for smoker controlled for; no consistent dose- Wheezing apart from colds mother 2 if only smoker mother response Cross-sectional study cough. The mother’s smoking had a greater effect than the father’s smoking. Burchfiel and colleagues (1986) have conducted a longitudinal study of 3,482 subjects from Tecumseh, Michigan. Subjects were initially between the ages of birth and 10 years and were followed up by questionnaire and examination 15 years after entry into the study. Age-specific incidence rates were calculated for a number of chronic respiratory symptoms, including cough, phlegm, wheeze, and bronchitis. Incidence rates for all symptoms were higher for children with two parental smokers when compared with children of non- smokers. Adjustment for potential confounding variables, including age, parental education, family size, and personal smoking, did not explain these results. British researchers (Leeder et al. 1976b) studying a birth cohort over a 5-year period demonstrated an increased incidence of wheez- ing among nonasthmatic children with two parents who smoked in comparison with children whose parents did not smoke, one parent who smoked, or parents whose smoking changed during the study (Leeder et al. 1976a). However, when this association was examined by logistic regression with control for. other factors, parental smoking was not a significant predictor of wheeze or of asthma. McConnochie and Roghmann (1984) performed a retrospective cohort study to examine the influence of mild bronchitis in early childhood on wheezing symptoms 8 years later when the subjects had reached a mean age of 8.3 years. Involuntary smoking was a significant predictor of current wheezing (odds ratio 1.9). Ina related study (McConnochie and Roghmann 1985) with these same children, involuntary smoking did not affect lower respiratory tract illness experience. In a study of 650 children aged 5 to 10 years (Weiss et al. 1980), a significant trend in the reported prevalence of chronic wheezing with current parental smoking was found; the rates were 1.9 percent, 6.9 percent, and 11.8 percent for children with zero, one, and _ two parents who smoked, respectively. Although the data given are for all households, when the analysis was restricted to those households where neither parent reported symptoms, the results were identical. The stability of the findings with this restriction suggests that reporting bias introduced by parental symptoms was not responsible for the observed results. Schenker and coworkers (1983) examined the influence of parental smoking and symptoms on the reporting of chronic respiratory symptoms of cough, phlegm, and persistent wheezing in children. These investigators found that the mothers were more likely than the fathers and symptomatic mothers were more likely than asymptomatic mothers to report these symptoms in their children. 47 Parental smoking had no significant effects on chronic respiratory toms. W nebowits and Burrows (1976) assessed the effects of household ry symptoms in 626 Tucson children members’ smoking on respiratory 81 C younger than 15 years of age. Children from homes with current smokers had higher symptom rates than those from homes with ex- smokers and with never smokers. However, the effect of household smoking type was statistically significant only for persistent cough. In a general population study, Schilling and colleagues (1977) reported no association between wheeze and involuntary smoking. Ware and associates (1984) enrolled 10,106 children between 6 and 9 years of age from six U.S. cities in a prospective study. The prevalence of persistent cough and persistent wheeze, measured. at the second examination, was higher in children whose parents smoked. The effect was greater for maternal smoking than for paternal smoking. Symptom prevalence rates increased linearily with the number of cigarettes smoked daily by the mother. In a multiple logistic model, the effect of maternal smoking persisted after adjustment for reported illness in the parents. Dodge (1982), studying third and fourth grade children in Arizona, found that symptoms, including wheeze, were related to both the presence of symptoms in the parents and the number of smokers in the household. In summary, children whose parents smoke had a 30 to 80 percent excess prevalence of chronic cough or phlegm compared with children of nonsmoking parents. For wheezing, the increase in risk varied from none to over sixfold among the studies reviewed. Many studies showed an exposure-related increase in the percentage of children with reported chronic symptoms as the number of parental smokers in the home increased. Misclassification as nonsmokers of children who are actively smoking could bias the results of these studies. Adolescent smokers may be reluctant to accurately report their smoking habits, and more objective measures of exposure may not help to distinguish active experimentation with cigarettes from involuntary exposure to smoke (Tager 1986). Although misclassifica- tion of children who are actively smoking as nonsmokers must be considered, many studies showing a positive association between parental smoking and symptoms in children, including children at ages before significant experimentation with cigarettes is prevalent. In addition, many studies (Bland et al. 1978; Weiss et al. 1980; Charlton 1984; Schenker et al. 1983; Dodge 1982; Burchfiel et al. 1986) found significant effects of parental smoking after considering active smoking by the children. Chronic respiratory symptoms represent an immediate health burden for the child. However, the long-term significance of chronic respiratory symptoms for the health of the child is unclear. Most 48 available data are cross-sectional, and followup studies of chronically symptomatic children are necessary to determine the long-term health consequences of chronic respiratory symptoms. Pulmonary Function In recent years, the effect of parental cigarette smoking on pulmonary function in children has been examined in cross-sectional studies (Table 3) and a few longitudinal studies. The cross-sectional studies have demonstrated lower values on tests of pulmonary function (FEV75%, FEVi, FEF 25-75, and flows at low lung volumes) in children of mothers who smoked compared with children of non- smoking mothers. The longitudinal studies (Table 4) have confirmed the cross-sectional results and provide some insight into the implica- tions of the cross-sectional data. Dose-response relationships have been found in both cross-section- al and longitudinal studies (Tager et al. 1979; Weiss et al. 1980; Ware et al. 1984; Berkey et al. 1986); the level of function decreases with an increasing number of smokers in the home. As would be anticipated from the mother’s greater contact time with the child, maternal smoking tends to have a greater impact than paternal smoking. Younger children seem to experience greater effects than older children (Tager et al. 1979; Weiss et al. 1980), and in older children the effects of personal smoking may be additive with those of involuntary smoking (Tager et al. 1979, 1985). As noted by Tager (1986), the effect of maternal smoking on lung function may vary with the child’s sex. Some studies have reported greater effects on flows at lower lung volumes in girls than in boys (Burchfiel et al. 1986; Tashkin et al. 1984; Yarnell and St. Leger 1979; Vedal et al. 1984). Flows at higher lung volumes seem more affected in boys (Burchfiel et al. 1986; Yarnell and St. Leger 1979; Berkey et al. 1986; Tashkin et al. 1984). Whether these sex effects represent differences in exposure, differences in susceptibility to environmental cigarette smoke, or differences in growth and devel- opment is unclear. Tager and colleagues (1983) followed 1,156 children for 7 years to determine the effect of maternal smoking on the growth of pulmo- nary function in children (Figure 2). After correcting for previous level of FEV:, age, height, personal cigarette smoking, and correla- tion between mother’s and child’s pulmonary function level, mater- nal smoking was associated with a reduced annual increase in FEV: and FEF2s7s, using two separate methods of analysis. If the effect of maternal smoking is maintained to 20 years of age, then a 3 to 5 percent reduction of FEV, and FEF 2-75 due to maternal smoking would be projected. The validity of this projection remains to be established. Because few mothers changed their smoking habits, the 49 TABLE 3.—Pulmonary runcuon in children exposed to involuntary smoking Study Subjecta Pulmonary function measured Outcome Comments Schilling et al. 816 children, aged 7-17, FEV, as percent predicted No effect of parental smoking No control for aibship size or (1977) Connecticut and South correlation of sibling pulmonary Carolina, United States function; for children who never smoked, Vinazs0 significantly leas in children with smoking mothers Tager et al. 444 children, aged 5-19, MMEF in standard deviation Significant effect of parental Controlled for sibahip size and (1979) East Boston, Massachusetts, unite smoking correlation of sibling pulmonary United States function Weiss et al. 650 children, aged 5-9, East MMEF in standard deviation Significant effect of parental Controlled for sibehip size and (1980) Boston, Massachusetts, units smoking correlation of sibling pulmonary United States function Vedal et al. 4,000 children, aged 6-13, FEV,, FVC, Vroaxso, Vmax, FVC positively associated, flows Flows dose-response with (1984) United States ‘Vinax90 negatively associated amount smoked by mother Lebowitz and 271 households, complete FEV,, FVC, Vinesso, Vinax7s No effect of parental smoking Suggestion: may be real Burrows histories of parent smoking derived from MMEF V curves, differences in indoor levels of (1976) and pulmonary function of as standard deviation units exposure compared with more children, age >6, Tucson, northerly climates Arizona, United States Lebowitz et al. 229 children, Tucson, FEV,, z score No effect of parental smoking Higher levels of pulmonary (1982) Arizona, United States function for children of smoking parents than for non- amoke-exposed children on food TABLE 3.—Continued Study Subjects Pulmonary function measured Outcome Comments Dodge 658 children, aged 8-10, FEV, by age change No effect of parental smoking Potential participation rate (1982) Arizona, United States FEV ,/H*/year bias; cross-sectional data not controlled for child height; annual FEV,/H’ at ages 8, 9, and 11 consistently greater in nonsmoking households than two-parent smoker households; statistical test not significant Tashkin et al. 1,080 nonsmoking, Vrasx, Venax7, Vinex2s, FEF 2-75 Decreased Vmax, Vmax2s for boys, No effect of paternal smoking (1984) nonasthmatic children, Los and FEF 225, Vmax1s for girls Angeles, United States with amoking mother at least Chen and Li 571 children, aged 8-16, FEV, and MMEF Significantly decreased FEV, Adjusted for child’s own (1986) China and MMEF in children exposed smoking, gas stoves, and to paternal cigarette emoke perental symptoms Haseelblad et al. 16,689 children, aged 5-17, FEV, as percent predicted Significant effect of maternal Large number of children (1981). seven geographic regions, but not paternal smoking excluded for invalid pulmonary United States function data or missing parental smoking data Speizer et al. 8,120 children, aged 6-10, FVC and FEV, as percent No effect for FEV, or FVC Recent analysis demonstrated (1980) six U.S. cities predicted an effect for FVC and FEV, Lebowitz 117 families, Tucgon, FVC and FEV, No effect of parental smoking Also assessed, TSP and ozone (1984) Arizona, United States rates had little effect Ekwo et al. 1,355 children, aged 6-12, FEV,, FVC No effect of parental smoking Data for this outcome not (1983) Towa City, Iowa, United specifically analysed; increased States bronchial responsiveness among smoke-exposed children Spinaci et al. 2,885 echoolchildren, Turin, FEV, Statistically significant effect of No passive smoking effect (1985) Italy maternal smoking difference between boys and girls os TABLE 4.—Pulmonary function in children exposed to involuntary smoking; longitudinal studies Study Tager et al. (1983) Ware et al. (1984) Berkey et al. (1986) Burchfiel et al. (1986) Subjecta 1,156 children, aged 5-10 at initial survey, Eaat Boston, Massachusetts, United States 10,000 children, aged 6-11, six US. cities 7,834 children, aged 6-10, six USS. cities 3,482 children, aged 0-10, Tecumseh, Michigan, United States Pulmonary function meagured FEV,, FEF2s-75 FVC, FEV, FVC, FEV, FVC, FEV), Vmaxso Outcome Significantly decreased FEV, and FEF2s-7s growth rate for children of smoking mothers FVC positively associated with amoking; FEV, negatively associated with smoke exposure Slightly higher FVC level, slightly lower FEV, level in smoke-exposed; growth of both decreased by smoke expoeure FEV, level and growth decreased by maternal smoking Comments ‘T-year followup; no effect of paternal smoking; magnitude roughly 4 to 5 percent FEV, dose-response with amount smoked by mother; magnitude of effect estimate 6 percent Consistent with 3 percent deficit in FEV, growth Dose-response in male children with number of parental smokers = & a a ° (183) “(151) 90 | : J i Tt Lowest 20% Middie 60% Highest 20% Distribution of 6-year mean FEV, sd a Average FEV% predicted Percentage of children with currently smoking mothers & g °o FIGURE 2.—Percentage of children with mothers who were current cigarette smokers at initial examination (black columns) and sixth examination (white columns), according to distribution of mean age, height, and sex- corrected FEV, over the first six examinations NOTE: Lowest 20%, middle 60%, and highest 20% refer to children with values in the bottom one-fifth, middle three-fifths, and upper one-fifth, respectively, of the mean FEV, distributi bers in p th indicat number of children in each group; the three circles represent the average percent predicted values of FEV, for the three groups; results for male and fe le child were bined, b a b sexes was not significant. SOURCE: Tager et al. (1983). sae, study could not establish the ages at which children were most vulnerable to exposure to tobacco smoke. Ware and colleagues (1984) followed 10,106 white children for two successive annual examinations as part of the Harvard Air Pollution Health Study in six USS. cities. The forced vital capacity was significantly higher for children of mothers who were either current smokers or ex-smokers. However, children whose mothers were current smokers had a 0.6 percent lower mean FEV: at the first examination and 0.9 percent lower mean FEV: at the second examination. Maternal smoking had a greater effect than paternal smoking, although the effects of both were significant. The changes in level of FEV: observed were small. For exposure to a mother who smoked one pack of cigarettes per day, the FEV: was estimated to be decreased by less than 1 percent, or 10 to 20 mL for a child with an FEV) between 1.5 and 2.5 liters. Projecting the effect cumulatively to age 20 yields an approximately 3 percent deficit. This effect is comparable to that observed by Tager and colleagues (1983). These small average effects may underestimate the effects on populations of susceptible children. 53 A more extensive analysis of longitudinal data from the Harvard cohort was performed using a mathematical model to describe lung growth (Berkey et al. 1986). This analysis included 7,834 children between 6 and 10 years of age who were evaluated from two to five times over a 5-year period. The model estimated that a smoke- exposed child at age 8 would have an FEV:0.81 percent lower than a non-smoke-exposed child, and growth of FEV: would be 0.17 percent lower per year. Both effects were statistically significant. For an 8- year-old child with an FEV: of 1.62 liters, these results translate into a deficit of 18 mL in FEV: and of 3 mL in annual increase in FEV. The magnitude of the maternal smoking effect is consistent with a deficit in FEV: of 2.8 percent in naturally attained growth, if the effect is sustained throughout childhood. Burchfiel and colleagues (1986) have conducted a longitudinal study of 3,482 children observed over a 15-year period in Tecumseh, Michigan. The mean increase in FEV: for nonsmoking boys between the ages of 10 and 19 years was 82.3, 76.2, and 74.5 ml. per year for subjects with zero, one, and two smoking parents, respectively. Boys with one parent who smoked experienced 92.6 percent and boys with two parents who smoked experienced 90.5 percent of the growth in FEV seen in male children with nonsmoking parents. Effects of parental smoking were not found in girls. The available data demonstrate that maternal smoking reduces lung function in young children. However, the absolute magnitude of the difference in lung function is small on average. A small reduction of function, on the order of 1 to 5 percent of predicted value, would not be expected to have functional consequences. However, some children may be affected to a greater extent, and even small differences might be important for children who become active cigarette smokers as adults. A minority of adult cigarette smokers develop chronic obstructive lung disease, and factors influencing lung growth and development during childhood might predispose to disease in adulthood (Samet et al. 1983; Speizer and Tager 1979). In Figure 3 is depicted a model of growth and decline in pulmonary function from childhood through adulthood, as measured by the FEV3. Pulmonary function peaks in early adult life and declines steadily thereafter in both smokers (curve B) and nonsmokers (curve A). In people who develop chronic lung disease (curve C), a more rapid decline has occurred. Childhood factors could predispose to the development of disease by reducing the functional level at which decline begins or by increasing susceptibility to cigarette smoke and increasing the rate of decline. Thus, in this model, small decrements in the maximally attained level of pulmonary function may be important in identifying the susceptible smoker. However, the prerequisite longitudinal studies needed to test this hypothesis have not yet been conducted. 54 FEV, as percent , of value at age 20-25 // Disabitity 25 & 5 10 15 20 30 40 50 60 70 80 Age (years) FIGURE 3.—Theoretical curves representing varying rates of change in FEV, by age NOTE: Curve A, normal decline in FEV, (forced expiratory vol inl ); curve B, Hi FEV, with cigarette smoking; curve D, the effect of smoking cessation, also seen in disabled individuals (curve Ei disability-related decline often continues as a variable rate (curves C and F). SOURCE: Speizer and Tager (1979). Bronchoconstriction Nonspecific bronchial responsiveness has been considered a poten- tial risk factor for the development of chronic obstructive lung disease in both adults and children (US DHHS 1984). This physiolog- ic trait may be influenced by environmental exposures such as involuntary smoking by children and active smoking by adults, and by respiratory infections at all ages. Asthma is a chronic disease characterized by bronchial hyperre- sponsiveness. Epidemiologic studies of children have shown no consistent relationship between the report of a doctor’s diagnosis of asthma and exposure to involuntary smoking. Although one study showed an association between involuntary smoking and asthma (Gortmaker et al. 1982), others have not (Schenker et al. 1983; Horwood et al. 1985). This variability may reflect differing ages of the children studied, differing exposures, or uncontrolled bias. In several recent studies (Murray and Morrison 1986; O’Connor et al. 55 1986; Weiss et al, 1985; Martinez et al. 1985; Ekwo et al. 1983), nonspecific bronchial responsiveness Was examined in relationship to involuntary smoking. The results of these studies suggest that exposure to maternal cigarette smoking 16 associated with increased nonspecific airways responsiveness. Some reports suggest that the increased responsiveness is present only in children known to be asthmatic (Murray and Morrison 1986; O’Connor et al. 1986), est that the increased responsiveness 1s seen in thers 5 wi children Bkwo et al. 1983; Martinez et al. 1985). The pathophysi- ological mechanisms underlying the increased responsiveness and the long-term consequences of the increased responsiveness remain unknown. This section reviews the studies on asthma and on i esponsiveness. oro or and noworkers (1982) studied the relationship between parental smoking and the prevalence of asthma in children up to 17 years of age. Random community-based. populations in Michigan (3,072 children) and Massachusetts (894 children) were surveyed. Parents reported on their own smoking habits and on the asthma histories of their children. Biased reporting by parents who smoked was assessed by examining the relationship between parental smoking and other conditions, and considered not to be present. Asthma prevalence declines with age, and asthmatic children are unlikely to tolerate active smoking; therefore, misclassification of actively smoking asthmatic children as nonsmokers seems unlikely. In comparison with children of nonsmokers, children whose parents smoked were more likely to have asthma (relative risks of 1.5 and 1.8 for Michigan and Massachusetts children, respectively) and severe asthma (relative risks of 2.0 and 2.4, respectively). The investigators estimated that between 18 and 23 percent of all childhood asthma and 28 and 34 percent of severe childhood asthma is attributable to exposure to maternal cigarette smoke. Schenker and coworkers (1983) studied 4,071 children between 5 and 15 years of age in western Pennsylvania. These investigators found no relationship of parental smoking to the occurrence of asthma, after adjustment for potential confounding factors. Horwood and coworkers (1985) conducted a cohort study of 1,056 children in New Zealand who were followed from birth to age 6 years. A family history of allergy and male sex were the only significant predictors of incident cases of asthma. Neither parental smoking nor respiratory illnesses were predictive of the occurrence of asthma in this investigation. A recently reported cross-sectional study by Murray and Morrison (1986) suggests a mechanism by which maternal cigarette smoking might influence the severity of chi dhood asthma. These investiga- tors studied 94 children, aged 7 to 17 years, with a history of asthma. The children of mothers who smoked had 47 percent more symp 56 Mother Nonsmoker Smoker PC zo history 16 gus oOo mg/mL oo , & ‘re 00 ° = nm too B84 00 05 bo ° ° o 0.25 ba O° ° 000 0.125 jus ° oo 0.06 bw ° 0.03 j= 0 tee p=0.002 FIGURE 4.—PC,, in two groups of children with a history of wheezing NOTE: Mothers of 32 were nonsmokers; mothers of 10 were smokers. SOURCE: Murray and Morrison (1986). toms, a 13 percent lower FEV:, and a 23 percent lower FEF 2-75 than the children of nonsmoking mothers. Forty-one children, who had been able to discontinue medication and had no recent respiratory illness, underwent a histamine challenge test. There was a fourfold greater responsiveness to histamine among the asthmatic children of mothers who smoked (Figure 4) compared with asthmatic children of nonsmoking mothers. Dose-response relationships were present for all outcome variables in this study: symptoms, pulmonary function, and airways responsiveness. The differences between children of smoking mothers and children of nonsmoking mothers were greatest in the older children. The father’s smoking behavior did not influence the child’s asthma severity. The sample of asthmatic children with mothers who smoked was small (N=10), and only 41 of 96 children had histamine challenge tests. Given the heterogeneity of asthma, the variable nature of bronchial hyperreactivity in asthma, and the potential for biased selection, these results must be interpreted with caution. O’Connor and coworkers (1986) studied 286 children and young adults, 6 to 21 years of age, drawn from a community-based sample, 57 and confirmed the findings of Murray and Morrison (1986). Bronchi- al responsiveness was measured with eucapneic hyperpnea to subfreezing air. Among the 265 subjects without asthma there was no significant relationship between maternal cigarette smoking and nonspecific bronchial responsiveness. However, in the 21 subjects with active asthma, maternal smoking was significantly associated with increased levels of bronchial responsiveness. In a study of 1,355 children 6 to 12 years of age, significant increases in FEV and FEF 2-75 were observed following isoproterenol administration in children whose parents smoked (Ekwo et al. 1983). Increases after isoproterenol were not observed in children of nonsmoking parents. Weiss and coworkers (1985) evaluated 194 subjects between the ages of 12 and 16 drawn from the same population as those reported by O’Connor and coworkers (1986), with eucapneic hyperpnea to subfreezing air as a test for bronchial responsiveness and allergy skin tests as a test for atopy. Subjects defined as atopic (any skin test wheal greater than or equal to 5 mm) had twice the frequency of lower respiratory illnesses in early childhood and were twice as likely to have a mother who smoked. However, there was no relationship between maternal smoking and increased bronchial responsiveness. Martinez and associates (1985) studied 170 9-year-old children in Italy. Nonspecific bronchial responsiveness to methacholine and allergy prick test positivity in these subjects was significantly associated with maternal cigarette smoking. These data suggest that maternal cigarette smoking may influence the severity of asthma; a mechanism for this effect may be through alteration of nonspecific bronchial responsiveness. Further investi- gation is needed to determine whether exposure to environmental cigarette smoke can induce asthma in children and whether ETS exposure increases the frequency or severity of attacks of broncho- constriction in asthmatics. The effect of involuntary smoking on increased bronchial responsiveness in asthmatics and in nonasth- matics has only recently been addressed. These initial data are provocative, but the magnitude of the effect, the target population at risk, the underlying mechanisms, and the long-term consequences have not been described. Furthermore, the complex interrelation- ships among respiratory illness, atopy, parental smoking, and airways responsiveness have not been clarified and require further study. Ear, Nose, and Throat Five studies (Said et al. 1978; Iverson et al. 1985; Kraemer et al. 1983; Black 1985; Pukander et al. 1985) show an excess of chronic 58 middle ear effusions and diseases in children exposed to parental smoke. Said and colleagues (1978) questioned 3,920 children between 10 and 20 years of age about prior tonsillectomy or adenoidectomy, considered an index of frequent upper respiratory or ear infections. The investigators reported that, in general, this surgery was performed before the children were 5 years old. The prevalence of prior surgery increased with the number of currently smoking parents in the home. Iverson and coworkers (1985) prospectively studied 337 children enrolled in all day-care institutions in a municipality over a 3-month period to evaluate the importance of involuntary smoking for middle ear effusion in children. Middle ear effusion was assessed with tympanometry, and the overall prevalence was found to be approxi- mately 23 percent. Although various indoor environmental factors were assessed in this investigation, only parental smoking was significantly associated with middle ear effusion. The effect of parental smoking persisted with control for the number of siblings. The overall age-adjusted odds ratio was 1.6 (95 percent confidence interval 1.0-2.6). In 5- to 7-year-old children, 10 to 36 percent of all chronic middle ear effusions could thus be attributed to smoking on the basis of these results. Kraemer and coworkers (1983) performed a case-control study of 76 children to examine the relationship of environmental tobacco smoke exposure to the occurrence of persistent middle ear effusions. Frequent ear infections, nasal congestion, environmental tobacco smoke exposure, and atopy were all more frequent in children with ear effusions. The effect of involuntary smoking was observed only if nasal congestion was present, and was greatest in children who were atopic. Black (1985) performed a case-control study of glue ear with 150 cases and 300 controls. Parental smoking was associated with a relative risk of 1.64 (95 percent C.I. 1.03-2.61) for glue ear. In Finland, Pukander and coworkers (1985) conducted a case-control study of 264 2- to 3-year-old children with acute otitis media and 207 control children and found an association between parental smoking and this acute illness. These studies are consistent in their demonstration of excess chronic middle ear effusions, a sign of chronic ear disease, in children exposed to parental cigarette smoke. Potential confounding factors for middle ear effusions should be examined carefully in future studies. The long-term implications of the excess middle ear problems deserve further study. 59 Adults Acute Respiratory Illness There are no studies of acute respiratory illness experience in adults exposed to environmental cigarette smoke. Cough, Phiegm, and Wheezing Few studies have addressed the relationship of chronic respiratory symptoms in nonsmoking adults with environmental tobacco smoke exposure. Schilling and colleagues (1977) found that symptoms in adult men and women were related to personal smoking habits and that the occurrence of cough, phlegm, or wheeze in nonsmokers was not related to the smoking habits of their spouses. Schenker and colleagues (1982) confirmed these results in a telephone survey of 5,000 adult women in western Pennsylvania. Pulmonary Function White and Froeb (1980) reported on 2,100 asymptomatic adults drawn from a population enrolled in a physical fitness program (Table 5). They reported statistically significant decreases in FEV: and maximum midexpiratory flow rate (MMEF) as a percent of predicted in nonsmokers exposed to tobacco smoke in the work environment for at least 20 years compared with nonsmoking workers not exposed. The magnitude of effect was comparable to that of actively smoking 1 to 10 cigarettes per day. However, the absolute magnitude of the difference in mean levels of function between the smoke-exposed group and the unexposed group was small: 160 mL (5.5 percent) for FEV: and 465 mL per second (13.5 percent) for MMEF. Carbon monoxide levels were measured in selected work- places and ranged from 3.1 to 25.8 ppm. The study population was self-selected, and the exposure classification was crude and did not account for people who changed jobs. It is unclear how the ex- smokers in the population were handled in the analysis. Kentner and coworkers (1984) performed a cross-sectional investigation on 1,351 workers and found no influence of involuntary smoking on pulmonary function. In this study, involuntary smoking at home and at work was considered. Comstock and colleagues (1981) examined 1,724 subjects drawn from two separate studies in Washington County, Maryland. Male and female nonsmokers married to smokers did not have a signifi- cantly increased risk of having an FEV; less than 80 percent of predicted or an FEVi/FVC ratio less than 70 percent. Schilling and colleagues (1977) also did not find an effect of involuntary smoking in adults. Effects were not examined within strata defined by age in either of these studies. 60 19 TABLE 5.—Pulmonary function in adults exposed to involuntary smoking Study Subjects Pulmonary function measured Outcome Comments White and Froeb (1980) Comstock et al. (1981) 2,100 adults, San Diego, California, United States 1,724 adults, Washington County, Maryland, United States FVC, FEV,, and MMF as percent predicted FEV, as percent predicted Significant effect of office exposure to involuntary smoke No effect of wives’ smoking on husband’s pulmonary function Potential selection bias; only current cigarette smoke exposure assessed; treatment of ex-emokers unclear Includes adults aged 20+ Cross-sectional study Kauffmann et al. (1983) Brunekreef et al. (1988) 7,818 adults, selected subgroups, seven cities, France 173 adults, subgroups of larger study, the Netherlands FEV,, FVC, and MMEF Peak flow, inspiratory vital capacity (IVC), FEV,, and MMEF All measures significant effect in wives of emoking husbands; only MMEF significant in husbands of smoking wives Significant effect in wives of smoking husbands for peak flow FEV, crosa-sectionally; no effect longitudinally Not height adjusted; dose- response to amount of husbands’ smoking for MMEF in wives; no effect below age 40 Cross-sectional study Small sample size Kentner et al. (1984) 1,851 adult office workers, Germany FVC, FEV, No effect of work exposure on pulmonary function Cross-sectional study Kauffmann and colleagues (1983) suggested that the effects of exposure from a spouse who smoked may be manifest only after many years of exposure. These investigators assessed the effects of marriage to a smoker in 7,818 adults drawn from several cities in France. Among 1,985 nonsmoking women aged 25 to 59, 58 percent of whom had husbands who smoked, the level of MMEF was significantly reduced in women married to smokers compared with women married to nonsmokers; this effect did not become apparent until age 40. The reduction was small, on average. Recently, studying another population, Kauffmann and colleagues (1986) suggested that the FEVi/FVC ratio may be a more sensitive test for detecting differences between exposed and nonexposed subjects, particularly in those with symptoms of wheezing; however, this suggestion has not been evaluated in other populations. Brunekreef and coworkers (1985), from the Netherlands, reported on 173 nonsmoking women who were participants in a larger longitudinal study of pulmonary function. The women were classi- fied by whether they were or were not exposed to tobacco smoke at study onset or at followup. Cross-sectionally, significant differences in pulmonary function were observed between smoke-exposed and nonexposed women. However, the rate of decline of lung function juring the followup period was not affected by tobacco smoke exposure in the home. This study had a small number of subjects and inadequate statistical power to detect effects of exposure on rate of decline that were not extremely large. Jones and colleagues (1983) selected women with either high or low FEVs from a population-based longitudinal study in Tecumseh, Michigan. Exposure to cigarette smoke at home from husbands who smoked was not significantly different in the two groups of women. Nonsmoking men who participated in the Multiple Risk Factor Intervention Trial had significantly lower levels of pulmonary function if their wives smoked in comparison with similar men whose wives did not smoke (Svendsen et al. 1985). The physiologic and clinical significance of the small changes in pulmonary function found in some studies of adults remains to be determined. The small magnitude of effect implies that a previously healthy individual would not develop chronic lung disease solely on the basis of involuntary tobacco smoke exposure in adult life. Whether particular characteristics increase susceptibility, such as childhood exposures or illnesses, atopy, reduced pulmonary function from whatever cause, and increased airways responsiveness, remains unknown. These small changes may also be markers of an irritant response, possibly transient, to the irritants known to be present in environmental tobacco smoke. 62 Bronchoconstriction Normal Subjects Only limited data have been published on the acute effects of inhalation of environmental tobacco smoke on pulmonary function in normal subjects (Table 6) and none on bronchial responsiveness. The available data have been obtained in exposure chambers under carefully monitored and controlled circumstances (Pimm et al. 1978; Shephard et al. 1979; Dahms et al. 1981). Pimm and colleagues (1978) exposed nonsmoking adults to smoke in an exposure chamber. Relatively constant levels of carbon monoxide (approximately 24 ppm) were achieved in the chamber during involuntary smoking. Peak blood carboxyhemoglobin levels were always less than 1 percent in these subjects before smoke exposure, but were significantly greater after the study exposure. Lung volumes, flow volume curves, and heart rates were measured for all subjects. Measurements were made at rest and following exercise under control and smoke-exposure conditions. Flow at 25 percent of the vital capacity was reduced at rest in men and with exercise in women. Although statistically significant, the magnitude of the change was small: a 7 percent decrease in flow in men and 14 percent in women. Shephard and coworkers (1979) utilized a similar cross-over design in a chamber of exactly the same size as that used by Pimm and associates. Their results were similar, with a small (3 to 4 percent) decrease in FVC, FEV:, Visaxs0, and Vmax. They concluded that these changes were of the magnitude anticipated from exposure to the smoke of less than one-half of a cigarette in 2 hours (the exposure anticipated for an involuntary smoker). Dahms and colleagues (1981) used a slightly larger chamber and an exposure with an estimated peak carbon monoxide level of approximately 20 parts per million. They found no change in FVC, FEV, or FEF2s-s in normal subjects after 1 hour of exposure. The active smoker manifests acute responses to the inhalation of cigarette smoke; thus, high-dose involuntary exposure to tobacco smoke may plausibly induce similar responses in nonsmokers. The magnitude of these changes is quite small, even at moderate to high exposure levels, and it is unlikely that this change in airflow, per se, results in symptoms. Asthmatics Dahms and colleagues (1981) exposed 10 patients with bronchial asthma and 10 normal subjects to cigarette smoke in an environmen- ‘tal chamber. Pulmonary function was measured at 15-minute intervals for 1 hour after smoke exposure. Blood carboxyhemoglobin levels were measured before and after the l-hour exposure. ‘The 63 TABLE 6.—Acute effects on pulmonary function of passive exposure to cigarette smoke; normal subjects Study Type of exposure Magnitude of exposure Effects Comments Pimm et al. (1978) Shephard et al. (1979) Dahms et al. (1981) Chamber 14.6 m, furniture sparse, smoking machine in room As above Chamber 30 m, climate controlled Peak (CO) ~ 24 ppm; particulates >4 mg/m’ Low exposure: peak [CO] ~ 20 ppm, particulates ~ mg/m’; high exposure: [CO] ~ 31 ppm Room levels not measured; estimated at peak [CO] ~ 20 ppm Men: 5% increase FVC, 11% increase RV, 4% decrease Vinaxes during exercise Women: 7% decrease Vimax2s after exercise; no effects on VC, TLC, FVC, FEV,, Vmaxso Low exposure: 3% decrease FEV,, 4% decrease Vinaxso, 5% decrease Vinazzs with exercise; no increased effect with high exposure : 0.9% increase in FVC, 5.2% increase in FEV,, 2.2% increase in FEF at 1 hour Nonsmokers; average age, men 22.7, women 21.9; sham exposure as control Nonsmokers: average age, men 23, women 25; sham exposure as control; subject estimated inhalation ~ 1/2 cigarette/2 hours 10 nonsmokers; age range 24- 53 years; not blinded; no sham exposure carboxyhemoglobin levels in subjects with asthma increased from 0.82 to 1.20 percent. In normal subjects the increase was from 0.62 to 1.05 percent. The increases in carboxyhemoglobin in the two study groups were not significantly different. Asthmatic subjects had a decrease in forced vital capacity (FVC), FEV:, and MMEF to a level significantly different from their preexposure values. The decreases in asthmatic subjects were present at 15 minutes, but worsened over the course of the hour to approximately 75 percent of the preexpo- sure values. Normal subjects had no change in pulmonary function with this level of exposure. In this study, subjects were not blinded as to the exposure and were selected because of complaints about smoke sensitivity. Shephard and colleagues (1979), in a very similar experiment, subjected 14 asthmatics to a 2-hour cigarette smoke exposure in a closed room (14.6 m3). The carbon monoxide levels (24 ppm) were similar to those predicted in the study of Dahms and coworkers (1981). Blood carboxyhemoglobin levels were not measured. Subjects were randomized and blinded to sham (no smoke) and smoke exposure and tested on two separate occasions. Data were expressed as the percentage change from the sham exposure. Significant changes in FVC and FEV: were not observed between the sham and the smoke exposure periods, although 5 of 12 subjects did report wheezing or tightness in the chest on the day of smoke exposure. Wiedemann and associates (1986) examined nonspecific bronchial responsiveness to methacholine in 9 asthmatic subjects and 14 controls and the effect of acute involuntary smoking on nonspecific bronchial responsiveness. At the time of the study, all asthmatics were stable with normal or near normal pulmonary function. The subjects underwent baseline pulmonary function and methacholine challenge testing. On a separate day they were exposed to cigarette smoke for 1 hour at 40 to 50 ppm of carbon monoxide and underwent pulmonary function and methacholine challenge testing. Pulmonary function was not influenced by exposure. Nonspecific bronchial responsiveness decreased significantly, rather than increasing, a5 would be anticipated following an irritant exposure. Acute exposure in a chamber may not adequately represent exposure in the general environment. Biases in observation and the in selection of subjects and the subjects’ own expectations may account for the widely divergent results. Studies of large numbers of individuals with measurement of the relevant physiologic and exposure parameters will be necessary to adequately address the effects of environmental tobacco smoke exposure on asthmatics. Ear, Nose, and Throat There are no studies of chronic ear, nose, and throat symptoms in adults with involuntary smoking exposure. 65 Lung Cancer This section reviews the epidemiological evidence on involuntary smoking and lung cancer in nonsmokers, which has been derived from retrospective and prospective epidemiological studies. First, common methodological issues that apply to all these studies are considered. Second, for each type of study design, individual studies are reviewed for their methodological approach (Tables 7 and 8), findings associated with tobacco smoke exposure (Table 9, Figure 5), and strengths and limitations. Third, the lung cancer risk associated with involuntary smoking is examined as a low-dose exposure to cigarette smoke by combining the dose-response relationships for active smoking with the exposure data for involuntary smoking to predict the expected lung cancer risk due to involuntary smoking, This expected risk is then compared with the actual risks observed in studies of involuntary smoking. Finally, the existing epidemiological evidence is summarized and the plausibility of the association between lung cancer and involuntary smoking is evaluated on the basis of our current knowledge. Observed Risk General Methodological Issues For both retrospective and prospective studies, the common methodologic concerns are disease misclassification and misclassifi- cation of the subject’s personal smoking status or exposure to ETS. Disease misclassification, for example, refers to the incorrect classifi- cation of the lung as the primary site of a cancer that originated elsewhere. Disease misclassification is of greatest concern in studies in which the diagnosis of lung cancer was not histologically confirmed. Such misclassification tends to be random and to bias relative risk estimates toward unity (Copeland et al. 1977). Patients with lung cancer, or any disease associated with cigarette smoke exposure, may report exposure to ETS more frequently than controls because of bias in recall. Misclassification of the subject’s personal smoking status may occur in both retrospective and prospective studies; this misclassifi- cation refers to incorrectly classifying a subject as a nonsmoker when the subject is actually an ex-smoker or a current smoker, or to incorrectly classifying the subject as a smoker when the subject is a nonsmoker. Biochemical markers such as cotinine and _ nicotine, which can be used to detect unadmitted active smokers, are sensitive only to a recent exposure to tobacco smoke; thus, they are not particularly useful for identifying ex-smokers who deny their past smoking histories. Misclassification of smokers or ex-smokers as nonsmokers may produce the appearance of an involuntary smoking effect when, in fact, the true relationship is with active smoking. 66 TABLE 7.—Description of prospective studies Studies Factor Hirayama Garfinkel Gillis Source of subjects Census population, 29 Volunteers, 25 States, Health survey health districts, Japan United States participants, two urban areas, Scotland Nonsmoker population 91,450 (F) 176,739 (F) 827 (M) size (sex) 1917 ® Age range 240 35-84 45-64 Years of enrollment 1966 1959-1960 1972-1976 Last year of followup 1981, 1983 1972 1982 Method of followup Record linkage between Monitored by ACS Record linkage with risk factor records and _—-volunteers, death Registrar General death certificates certificates from files local/State health departments Verification of None Verified method of Local cancer registry histology for first 6 years’ followup Method and type of Interview (?): smoking Self-administered In-person interview: information obtained and drinking habits, questionnaire: amoking habits, dietary history, education, residence, symptoms of occupation, other occupational respiratory and health-related variables § exposure, smoking cardiovascular and medical history diseases Index of passive Husband’s smoking at Husband’s smoking Spouse's smoking at smoking entry: nonsmoker, ex- at entry: nonsmoker, entry: current or smoker, current current smoker, and never smoker, ex- smoker (cig/day) cig/day; ex-smokers amokers excluded excluded (quit >5 years before entry) Number of lung cancer 200 (F) 153 F) 6 MM), 8 &) deaths in nonsmokers SOURCE: Hirayama (1981a, 1983, 1984a, b), Garfinkel (1981), Gillis et al. (1984). Misclassification of involuntary smoking exposure refers to the incorrect categorization of exposed subjects as nonexposed and of nonexposed subjects as exposed. Most studies of lung cancer to date have used the number of cigarettes smoked by spouses as a measure of exposure to involuntary smoking, and thus have disregarded duration of exposure, exposure from other sources, and factors that influence exposure, such as proximity to the smokers or size and ventilation of the room where the exposure occurred. Moreover, all 67 TABLE 8.—Description of case-control studies Confirmed histology Case Control Index of passive Reapondent and —Pathological/ smoke: habits of Study Country Source and type Source and type type of interview cytological © Adenocarcinoma spouses and others Trichopouios Greece Chest and cancer Orthopedic hospital; 225 Self; not blinded 65% Presumed Current and former et al. (1981, hospitals; 77 NS ) NS; not matched none spouses (amount, 1983) yr); no other Correa et al. New Orleans, Hospitals; 30 NS (8 M, Same hospitals, non-tobacco- Self, and proxy 97% 54% among Current spouse (1983) United States 22 F) related diseases; 313 NS (case, 23%; women (type, amount, yr); (180 M, 133 F); matched for control, 1196); parents age, sex, race, hospital blinded Chan and Hong Kong Four hospitals; Orthopedic, same hospitals; Self; not blinded 82% 45% Not spouse Fung (1982) & NS (F) 189 NS; not matched specifically; one question: at home and at work Koo et al. Hong Kong Eight hospitale; Population; 187 NS; Self; not blinded 97% 59% Current and former (1983, 1984) 88 NS ® matched for age, race, sex, spouses (amount, socioeconomic status, yrs, hra); parents, residence district other cohabitants, coworkers (amount, yrs, hre) Kabat and United States Most from one NY Same hospital (7); non- Self; not blinded 100% 54% M Current spouse Wynder (1984) hospital; 134 NS; tobacco-related disease; 78 14% F of (present or past passive smoking data NS (25 M, 53 F); matched 134 NS amoking habits); on only 78 NS (25 M, for age, sex, race, hospital, current exposure at 53 FE) date of interview, home and work nonsmoking status 69 TABLE 8.—Continued Confirmed histology Case Control Index of passive Respondent and Pathological/ amoke: habits of Study Country Source and type Source and type type of interview cytological § Adenocarcinoma spouses and others Wu et al. Los Angeles, Population-based Population; 62 NS; matched _Self; not blinded 100% 100% Current and former (1985) United States registry; 29 NS (F) for age, race, sex, spouses (amount, neighborhood yrs); parents, cohabitants (amount, yrs), coworkers (hr/day, yrs) Garfinkel et New Jersey, Four hospitals; Same hospitals, colorectal Self (case, 12%; 100% 65% Current spouse or al. (1985) Ohio, United 134 NS (F) cancer patients; 402 NS; control, ?) and cohabitant (total States matched for age, hospital, proxy; blinded and at home: nonsmoking status amount, yrs), other exposure, average hrs/day (at home, work, other) 5 and 25 yrs before diagnosis; childhood exposure OL TABLE 8.—Continued Confirmed histology Case Control Index of passive Respondent and Pathological/ smoke:;, habits of Study Country Source and type Source and type type of interview cytological Adenocarcinoma spouses and others Lee et al. United Hospital-based; 47 NS Same hospitals; 96 NS (30 Self, hospital ? ? Current spouse (1986) Kingdom (15 M, 32 F) M, 66 F); matched for age, inpatient (smoking habit sex, marital status, hospital _—interview; during admission Spouse, followup yr and maximum interview; not during marriage); specified other exposure at home, at work, during travel and leisure Akiba et al. Japan Hiroshima and Same cohort, noncancer or Self (case, 10%; 57% ? Current spouse (1986) Nagasaki bomb chronic respiratory disease; control, 12%) and (amount, age start, survivors; 103 NS (19 380 NS (110 M, 270 F); proxy; not blinded age stop, yrs M, 8 F) matched for age, sex, city cohabited); parents of residence, vital status, yr of death Pershagen Sweden National census of Two controls from each Self, and proxy 99% 57% Spouse lived with et al. Sweden and Swedish _—source; 347 NS; matched (case, almost all; longest (amount, (in press) Twin Registry, for year of birth, vital control, > 65%); yre); parents 67 NS ) status at followup end for not applicable, twin registry control mailed questionnaire TABLE 9.—Results from selected prospective and case- control studies; lung cancer risk associated with spouses’ smoking Study Spouses’ smoking Nonsmoker Ex-smoker 1-14/day 15-19/day 20+ /day Hirayama 10 14 14 16 19 (1984a) (0.9, 2.2)? (1.0, 2.0) (1.0, 2.4} (1.8, 2.71) Nonsmoker <20/day 20+ /day Garfinkel 1.0 13 11 (1981) (0.9, 1.9) (0.8, 1.6) Not exposed Exposed Gillis et al. Men 1.0 43 (1984) Women 10 10 Nonsmoker Ex-smoker 1-20/day 21+/day Trichopoulos et al. 10 19 19 2.5 (1983) (0.9, 4.1) (1.0, 3.7) (1.7, 3.8) Nonsmoker 1~40 pack-yr >41 pack-yr Correa et al. 10 1.5 3.1 (1983) (0.6, 3.8) (1.1, 8.5) No Yes Chan and Fung 1.0 0.8 (1982) (0.5, 3.1) Nonsmoker <35,000 hrs? >35,000 hra Koo et al. 138 1.0 (1984) (0.8, 2.4) (0.2, 2.7) No Yes Kabat and Wynder 1.0 0.9 (1984) (0.3, 2.1) Nonsmoker 1-20 yrs 21+ yrs Wu et al. 1.0 14 12 (1985) (0.4, 4.9) (0.4, 3.7) Nonsmoker Cigar/pipe <10/day 10-19/day >20/day Garfinkel et al. 1.0 12 12 lis (1985) (0.8, 1.7) (0:8, 1.6) (0.8, 1.5) (1.1, 4.0) No Yes Lee et al. 1.0 11 (1986) (0.5, 2.4) Nonamoker 1-19/day 20-29/day 30+/day Akiba et al. 10 13 15 21 (1986) (0.7, 2.3) (0.8, 2.8) (0.7, 2.5) Nonsmoker Low? High* Pershagen et al. 1.0 1.0 3.2 (in presa) (0.6, 1.8) (1.0, 9.5) * Numbers in parentheses are the 95 percent confidence limits. * Total exposure from spouses, cohabitants, coworkers. * Husband smoked < 15 cigarettes/day or 1 pack (50 g) of pipe tobacco/week or any amount during < 30 years of marriage. “Husband smoking > 15 cigarettes/day or 1 pack of pipe tobacco/week during > 30 years of marriage. 71 10 . . 9 Correa 8 7 #6 gs T Wu Garfinkel 2, T Trichopouios — Chan t . ' 7 i of 31 ft Lee Koo | j Akiba 1 | { j Kabet - 7 fF of i 4 7 oid aired tot bod pod 4 { ef ot | ' ! i i q 1 - ; tT ° ‘ fil bp tp ty bs Et Lt PP bo Sop opp RS es t j S* S$ Low*High 1-20 21+ 1-19 20-29 30+ 1-19 20+ Low High 1-20214 1-40 414 ee eR gay ya genta years per day per day Perday pack-years Smoking habits of spouses FIGURE 5.—Relative risks and 95 percent confidence intervals in case-control studies of passive smoking and lung cancer 1 S=amoker. * Low and high exposure levels are deacribed in Table 9. SOURCE: Chan and Fung (1962); Kebet and Wynder (1984); Lee et al. (1966); Koo et al. (1964); Wu et al. (1985); Akiba et: al. (1986); Garfinkel et al. (1985); Pershagen et al. (in preas); Trichopoulos et al. (1983); Correa et al. (1963), of the published studies have based involuntary smoking exposure measures on questionnaires without validation of these data with biochemical markers or environmentally measured concentrations of tobacco smoke constituents. Misclassification of involuntary smoking exposure is likely to be random and to bias the effect measures toward the null (Copeland et al. 1977). Misclassification of exposure to environmental tobacco smoke is inherent in epidemiological studies of involuntary smoking. Tobacco smoking has not been restricted in most indoor environments until recently, and exposure has been almost inevitable in the home, the workplace, or other locations. Studies with the biological markers . nicotine and cotinine confirm that tobacco smoke exposure is widespread; detectable levels of these markers are found even in people without reported recent exposure. Thus, the exposure vari- ables employed in epidemiological studies do not separate nonex- posed subjects from exposed subjects; instead, they discriminate more exposed groups from less exposed groups. As a result, the 72 epidemiological approach is conservative in estimating the effects of involuntary smoking. A truly nonexposed but otherwise equivalent comparison population has not been identified. The extent of the resulting bias cannot be readily estimated and probably varies with the exposure under consideration, which may be one reason for the variability in risk estimates obtained by different studies. Information bias is an added concern in case-control studies, since neither interviewer nor respondent bias can be ruled out. It is not feasible to blind interviewers to the case or control status of respondents because of the usually obvious manifestations of lung cancer and because of the setting in which some of the interviews are conducted. Moreover, blinding of interviewers and respondents to the study hypothesis is difficult because the majority of questions are concerned with exposure to tobacco smoke. The direction of the information bias may be dependent on the type of respondent. Self- respondents may be more apt to interpret their disease as related to exposure to tobacco smoke and thus overreport the exposure. However, the direction of the information bias is less clear when interviews are conducted with surrogate respondents. The ability of & surrogate to provide accurate information may depend on the relationship of the surrogate respondent to the subject, whether the surrogate lived with the subject during the time frame of the questions asked, the degree of detail requested, and the amount of time elapsed since the event in question (Gordis 1982; Pickle et al. 1983; Lerchen and Samet 1986). Surrogate respondents may mini- mize the reporting of their own smoking because of guilt, or may overreport about involuntary smoking exposure in an attempt to explain their relative’s illness. Thus, depending on the direction of the information bias, it may dilute or strengthen the effect being. measured (Sackett 1979). In general, however, the information on smoking status and on amount smoked provided by surrogates has been found to be fairly comparable to that provided by the individuals themselves (Blot and McLaughlin 1985). Finally, participants and nonparticipants in case-control studies may be inherently different with respect to their exposure to involuntary smoking because their awareness of the hypothesis under study may motivate the decision to participate. However, participants in case-control studies are generally not informed of the hypothesis under study. Spousal Exposure: Prospective Studies The Japanese Cohort Study Hirayama (1981a, 1983, 1984a) has presented data from a large cohort study that included 91,540 nonsmoking married women who were residents of 29 health districts in Japan. Subjects were 40 years 73 of age or older at enrollment in 1965; information was collected on smoking and drinking habits, diet (e.g., green-yellow vegetables, meat), occupation, and other health-related variables. The initial report on involuntary smoking was based on 14 years of followup (1966-1979). The husbands’ smoking histories were avail- able for 174 of 240 lung cancer cases identified among the non- smoking married women (Hirayama 1981a); this number increased to 200 with 2 additional years of followup (Hirayama 1983, 1984a). Results pertaining to the association of spouses’ lung cancer risk with the husbands’ smoking were essentially identical in the first and second reports. On the basis of the smoking habits of the husbands at entry, the 200 nonsmoking women were classified as married to a nonsmoker, an ex-smoker, or a current smoker. The lung cancer mortality ratios standardized by husband’s age were 1.00, 1.36, 1.42, 1.58, and 1.91 for women whose husbands were nonsmokers, ex-smokers, and daily smokers of 1 to 14, 15 to 19, and 20 or more cigarettes, respectively (one-sided p for trend, 0.002). Similarly significant dose-response trends were observed when the mortality ratios were standardized by age of the wives, by occupation of the husbands (agricultural, industrial, other), by age and occupation of the husbands, and by the time period of observation (1966-1977 versus 1978-1981). The risk of lung cancer among nonsmoking wives of smokers was reduced to 0.7 (two-sided p=0.05) if they ate green-yellow vegetables daily com- pared with 1.0 if they ate such vegetables less often than daily (Hirayama 1984b). No other characteristic of the wives (e.g., drinking habits, parity, occupation, nonvegetable dietary items) or of the husbands (e.g., drinking habits) was significantly predictive of lung cancer risk. Nonsmoking men whose wives were smokers also showed an elevated lung cancer risk. On the basis of 67 lung cancers in nonsmoking married men, the lung cancer mortality ratios were 1.00, 2.14, and 2.31 if their wives had never smoked or had smoked 1 to 19 cigarettes or 20 or more cigarettes per day, respectively (one- sided p for trend, 0.023) (Hirayama 1984b). This study has been critically discussed in correspondence since its initial publication. Because a detailed breakdown of the at-risk population was not presented in the initial report, the lung cancer mortality rate was thought by some to be higher in the unmarried nonsmoking women than in the nonsmoking women married to smokers (Rutsch 1981; Grundmann et al. 1981). This impression was clarified by the researcher (Hirayama 1981b,c,d) and shown to be the result of incorrect interpretation of data in the original paper. Other potential problems cited were sampling bias in the study cohort, misclassification in the diagnosis of lung cancer, misclassification of the nonsmoking status of wives, misclassification of involuntary 74 smoking exposure, failure to control for potential confounders, and inadequate statistical treatment of data. Each of these points of criticism is discussed below. MacDonald (1981a,b) questioned the representativeness of the 29 health districts selected in the study cohort and suggested that industrial pollution, such as asbestos exposure from shipbuilding industries specific to the selected health districts, may have biased the results. However, the levels of exposure to this factor would have to coincide with the husbands’ smoking level to explain the effect observed. Such an association seems unlikely. If the cohort were not representative, the generalizibility but not the validity of the findings would be challenged (Criqui 1979). The accuracy of the diagnosis of primary lung cancer on the basis of death certificates and the adequacy of the data without informa- tion on the histology of the tumor were questioned (Grundmann et al. 1981; MacDonald 1981a). From a sample of 23 cases, Hirayama (1981b) reported that the distribution by histology of lung cancer in nonsmoking women whose husbands smoked was similar to that in women who smoked. Failure to discriminate in some cases between primary and metatastic lesions to the lung may be a potential problem with disease diagnosis. Although Hirayama was unable to assess the accuracy of the diagnosis listed on the death certificate, there is no reason to believe that error in recording the causes of death of wives was influenced by the smoking habits of their husbands, and any misclassification is likely to be random. Inclusion of nonlung cancer cases would tend to bias the risk ratio toward unity or no effect (Barron 1977; Greenland 1980). The relatively high risks observed for nonsmokers whose husbands smoked led to speculation that Japanese women may report them- selves as nonsmokers when they actually smoke (Lehnert 1984). However, some assurance of the reliability of the smoking data provided by the Japanese women comes from an investigation in Hiroshima and Nagasaki (Akiba et al. 1986) that found strong concordance between smoking status reported by the women them- selves and that reported by their next of kin. Classifying nonsmoking women solely on the basis of the smoking habits of their current husbands probably does not quantify their exposure with precision because it accounts for only one of the many possible sources of tobacco smoke exposure. Moreover, using the number of cigarettes smoked per day by the husbands as a measure of exposure dose assumes that the husbands’ increasing daily cigarette consumption is directly related to an increasing ETS exposure of the wives (Kornegay and Kastenbaum 1981; Lee 1982b). The analyses were further criticized for not accounting for potential confounding factors such as socioeconomic status (SES) and exposure to indoor air pollutants (e.g., from heating and cooking 75 sources) (Sterling 1981). However, Hirayama showed a fairly consis- tent relationship between involuntary smoking exposure and lung cancer across SES categories. The role of indoor air pollutants could not be addressed directly in the study, but data from one health district in the study indicated no association between heating or cooking practices and the smoking habits of the husbands (Hirayama 1981b). The researcher’s failure to specifically describe the methods for age standardization in the initial report led to speculation that the statistical methods used were incorrect (Kornegay and Kastenbaum 1981; Mantel 1981; Tsokos 1981; Lee 1981); however, the calculations were later confirmed (Harris and DuMouchel 1981; Hammond and Selikoff 1981). The choice of stratification variables used for age standardization was also criticized because the husbands’ ages instead of the wives’ ages and 10-year age groups instead of narrower ones were used (Tsokos 1981; MacDonald 1981b). Later publications confirmed that similar results were obtained regardless of the method of standardization (Hirayama 1984a). The American Cancer Society Cohort Study A second prospective study (Garfinkel 1981) that examined the effects of involuntary smoking was the American Cancer Society (ACS) study of about 1 million people living in 25 States. A self- administered questionnaire on education, residence, occupational exposure, and smoking and medical history was completed by the study subjects upon enrollment. This report on involuntary smoking was based on 12 years of followup (1960-1972) and included 176,739 nonsmoking married women whose husbands’ smoking habits were available and whose husbands were never smokers or current smokers. In the total cohort of nonsmoking women, 564 lung cancer deaths occurred, and data on the husbands’ smoking habits were available for 153 (27.1 percent). Wives of ex-smokers and of cigar or pipe smokers were excluded from the analysis. A small, statistically nonsignificant increased risk for lung cancer was found for nonsmokers married to smokers. The mortality ratios for lung cancer in nonsmoking women were 1.0, 1.27, and 1.10 when the husbands were nonsmokers, daily smokers of fewer than 20 cigarettes, and daily smokers of 20-or more cigarettes, respectively. The results were essentially unchanged after accounting for the potential confounding effects of age, race, education, residence, and husband’s occupational exposure. The ACS study, like the Japanese study, was not designed to study the long-term effects of involuntary smoking. However, the ACS study does provide an estimate of the extent of misclassification of lung cancer. On the basis of medical record verification, the death 76 certificate diagnosis of lung cancer in nonsmoking women was incorrect for 12 percent of the cases. Although confirmation of diagnosis was sought only for the first 6 years of followup, the available data suggest that some misclassification of lung cancer occurred. To the extent that passive smoking is related to lung cancer in nonsmokers, inclusion of nonlung cancers would tend to dilute a true effect. A limitation of the ACS study is the nonavailability of smoking information on the husbands of a large proportion of the nonsmoking women who died of lung cancer. Because smoking habits are correlated with various social characteristics, this large loss of information may have created a bias in this study. The researcher stated that an index of tobacco smoke exposure based only on smoking habits of current husbands may be particularly inadequate for the United States, with its high rate of divorce and substantial proportion of women working outside the home. This speculation is supported by data from a group of 37,881 nonsmokers and ex- smokers who were members of a health plan in California. Friedman and colleagues (1983) stated that 47 percent of the nonsmoking women and 39 percent of the nonsmoking men married to smokers reported no exposure at home. Moreover, being married to a nonsmoker did not assure the absence of exposure to tobacco smoke, since 40 percent of the nonsmoking women and 49 percent of the nonsmoking men married to nonsmokers reported some exposure to tobacco smoke during the week. Thus, random misclassification could have biased the results toward unity and led to an underesti- mate of the effect of passive smoking. The Scottish Study Gillis and colleagues (1984) conducted a prospective cohort study of 16,171 Scottish men and women, aged 45 to 64 years, from two urban areas, who attended a multiphasic health screening clinic between 1972 and 1976. A questionnaire on smoking habits and symptoms of respiratory and cardiovascular diseases was completed at entry into the study. The preliminary analysis of involuntary smoking, representing 6 to 10 years of followup, was based on the 2,744 nonsmokers among the 8,128 subjects who lived as couples and could be paired according to smoking habits. Subjects who lived alone or whose partner did not participate and ex-smokers who had stopped smoking for 5 years or more were excluded. The nonsmokers were classified as nonsmokers not exposed to environmental tobacco smoke or as nonsmokers exposed to environmental tobacco smoke, according to the smoking habits of their spouses. A higher age-standardized lung cancer mortality rate was reported for nonsmoking men exposed to tobacco smoke (13 per 10,000) than 77 for nonsmoking men not exposed (4 per 10,000); however, no statistical tests were conducted because of the small number of cancers. Lung cancer rates were similar for nonsmoking women regardless of the status of their exposure to tobacco smoke (4 per 10,000). The extremely small number of observed lung cancer deaths (6 men, 8 women) limit the interpretation of the study’s findings. Spousal Exposure: Case-Control Studies Table 8 summarizes the case-control studies that have examined the relationship between involuntary smoking exposure and lung cancer. The Greek Study Trichopoulos and colleagues (1981, 1983; Trichopoulos 1984) examined the effect of involuntary smoking on lung cancer risk in a case-control study of 51 Caucasian female lung cancer patients (excluding adenocarcinoma and terminal bronchiolar carcinomas) from three chest hospitals and 163 female controls from an orthopedic hospital in Athens, Greece. All subjects were interviewed in person by one physician who questioned them regarding their personal smoking habits and those of their current and former husbands. Thirty-five percent of the cases were diagnosed only on the basis of clinical or radiologic information; the remainder were cytologically (37 percent) or histologically (28 percent) confirmed. Nonsmoking women were classified by the smoking habits of their current or former husbands. Husbands were nonsmokers if they had never smoked or had stopped smoking more than 20 years previous- ly, ex-smokers if they stopped 5 to 20 years previously, and current smokers if they were smoking or had stopped less than 5 years before the interview. Being never married, widowed, or divorced was equated as being married to a nonsmoker or an ex-smoker, depend- ing on the length of time in the category. The initial report was based on 40 nonsmoking cases and 149 nonsmoking controls. The odds ratios (ORs) for women married to nonsmokers, ex-smokers, current smokers of 1 to 20 cigarettes per day, and current smokers of 21 or more cigarettes per day were 1.0, 1.9, 2.4, and 3.4, respectively (two-sided p for trend, < 0.02). In a later report on 77 nonsmoking cases and 225 nonsmoking controls, the ORs were somewhat lower: 1.0, 1.9, 1.9, and 2.5, respectively (Trichopoulos et al. 1983; Trichopoulos 1984). The findings of this study were questioned because the diagnosis of cancer was not pathologically confirmed for 35 percent of the cases (Hammond and Selikoff 1981; Lee 1982b). The inclusion of cases that were not lung cancers would tend to dilute the results toward the null because they may not be related to involuntary smoking. 78 Terminal bronchial (alveolar) carcinoma and adenocarcinoma of the lung were excluded from the pathologically confirmed group; this exclusion may have been premature (Hammond and Selikoff 1981; Kabat and Wynder 1984), as the causal association between personal smoking and adenocarcinoma of the lung is well established CARC 1986). Because the controls were selected from a different hospital than were the cases, selection bias cannot be ruled out. Interviewer bias is also possible, since all subjects were interviewed by a single physician who knew the case or control status of each subject, and also knew the hypothesis under investigation. The index of exposure to tobacco smoke used in this study included the smoking habits of former and current husbands. Since the definition of ex-smokers excluded those who had stopped smoking recently (within the last 5 years), it was unanticipated that the risks observed for women whose husbands were ex-smokers (i.e., quit 5 to 20 years previously) were as high as for those whose husbands were current smokers. Additional information on the smoking habits of these ex-smokers would be valuable. The Louisiana Study The case-control study by Correa and colleagues (1983) was based on 1,338 primary lung cancer cases, of which 97 percent were pathologically confirmed. Controls (N=1,393) were matched to cases by race, sex, and age (+5 years) and were patients at the same hospitals as cases but without a diagnosis related to tobacco smoking. Standardized interviews were conducted with the subjects (76 percent of cases, 89 percent of controls) or their next of kin. Questions on occupation, residency, personal smoking and drinking habits, and smoking habits (including type of tobacco smoked and amount and duration of smoking) of the current spouse and parents were asked. Thirty nonsmoking ever-married lung cancer (excluding bron- chioalveolar cell) patients (8 men, 22 women) and 313 ever-married nonsmoking controls (180 men, 133 women) were classified according to their spouse’s total lifetime pack-years and current daily amount smoked at the time of interview. After adjusting for sex, ORs of 1.00, 1.48, and 3.11 were observed when spouses had smoked none, 1 to 40 pack-years, and 41 or more pack-years, respectively (two-sided p<0.05). The results based on current daily number of cigarettes smoked by spouses were similar. The study is limited by the small number of nonsmoking cases, but the consistency of the results for men and women strengthens the findings. Misclassification of involuntary smoking is possible because only smoking habits of the current husband were assessed, ignoring the effect of divorce, remarriage, and exposure from coworkers. Exposure from parents during childhood was determined, but case 79 numbers were too small for a meaningful analysis of this factor among nonsmokers. ' The Hong Kong Studies involuntary smoking was investigated in two studies conducted in Hong Kong (Chan et al. 1979; Chan and Fung 1982; Koo et al. 1983, 1984). Chan and colleagues (1979) examined the role of involuntary smoking among 84 female lung cancer patients and 139 orthopedic control patients, none of whom had ever smoked. Of the 84 nonsmoking cases, 69 (82 percent) were pathologically confirmed, and 38 of these 69 cases were adenocarcinoma of the lung. The controls were from the same hospitals as the cases, but were not individually matched to the cases on any characteristics. Cases and controls were questioned regarding their residence, education, occupation, cooking practices, and personal smoking habit. One question on exposure to others’ tobacco smoke was included: “Are you exposed to the tobacco smoke of others at home or at work?” The researchers reported that the controls lived with smoking husbands more frequently (47.5 percent) than the cases (40.5 percent) (OR 0.77), but did not explain how this question was used to classify the habits of the spouse alone. The method used to classify currently unmarried respondents (i.e., never married, wid- owed, divorced) with regard to exposure to their spouses’ smoking was not described, and it is not known if the nonsmoking cases and controls were comparable in terms of current marital and employ-. ment status. Thus, insufficient information on the measure used to assess ETS exposure, and on the comparability of the nonsmoking cases and controls, limits interpretation of this study’s results. The study by Koo and colleagues (1983, 1984) involved 200 Chinese female lung cancer patients who were identified from eight hospitals in Hong Kong; almost all cases were pathologically confirmed (97 percent). Among these women, 88 had never smoked, of whom 52 (59 percent) had adenocarcinomas of the lung. An equal number of “healthy” population controls, individually matched to cases by age (+5 years), socioeconomic status, and district of residence, were interviewed. Among the controls, 137 had never smoked. Using a semistructured questionnaire, taped interviews were obtained and information on residence, occupation, family and medical history, personal smoking habits, and smoking habits of all cohabitants and coworkers was elicited. ETS exposure was quanti- fied in hours and years according to who (i.e., husband, parents, in- laws, children, others) smoked in the subject’s presence and where 80 (ie., at home, at work) the exposure occurred. The analysis was based on a cumulative smoke exposure index (in total hours and total years) specific to place of exposure. The investigators concluded that there was no association between involuntary smoking and lung cancer in nonsmoking Chinese women, regardless of the index of smoke exposure used. A small, but statistically nonsignificant, increased risk (RR 1.24) was associated with any exposure to tobacco smoke. There were no significant differences between the cases and the controls in total hours or total years of exposure. The results remained unchanged when exposure hours were categorized into three levels of exposure. Odds ratios of 1.00, 1.28, and 1.02 were associated with no, low (<35,000 hours), and high (> 35,000 hours) exposure levels, respectively. There was no apparent trend of lung cancer risk with the age when exposure to tobacco smoke began. The ORs for never exposed and first exposed at ages 0 to 19, 20 to 39, and 40 or older were 1.00, 0.96, 1.53, and 0.91, respectively (Koo et al. 1984). Analysis by cell type suggested that the effects of involuntary smoking may be more pronounced for Kreyberg I tumors (squamous, small-cell, and large-cell carcinomas) (OR 1.47, 95 percent C.I. 0.64, 3.36) than for adenocarcinoma (OR 1.11, 95 percent C.I. 0.49, 2.50) (Koo et al. 1985), but these numbers were small. The design of this study addressed the criticisms of other studies that an index of involuntary smoking exposure based only on spouses’ smoking habits is inadequate, and broadened the exposure assessment to include all locations of tobacco smoke exposure. However, the cumulative exposure index created in this study may have limited validity. Unlike personal smoking, where there is essentially one source (personal smoking), one dose (usual or maximum amount smoked), and one duration of exposure (age at start and age at stop), ETS exposure derives from diverse sources at different doses and durations of exposure. The accuracy of the information on exposure to ETS will depend on the amount of detail requested, the age of the respondent, the temporal course of the exposure, and the source of the exposure. Weighing each type of exposure equally in a cumulative index (in total hours) may be incorrect because it assumes that all sources of exposure should be quantified in the same way and that each source of tobacco smoke contributes equally, disregarding intimacy of contact and proximity to smokers and conditions of exposure (e.g., room size, ventilatory factors). Thus, random misclassification of the exposure variable by inclusion of data from less relevant exposures than spousal smoking may obscure an association of involuntary smoking exposure with lung cancer risk. In this study, interviewer and respondent bias should also be considered because a structured questionnaire was not used. 81 An Ongoing Study of Tobacco-Related Cancers All of the cases of primary lung cancer in nonsmokers were selected (Kabat and Wynder 1984) from an ongoing case-control study of tobacco-related cancer conducted in five U.S. cities between 1971 and 1980 (Wynder and Stellman 1977). For each case, one control was individually matched by age (+5 years), sex, race, hospital, date of interview (+2 years), and nonsmoking status. Controls were selected from a large pool of hospitalized patients who were interviewed over the same time period as the cases and who had diseases not related to tobacco smoking. Information on demo- graphic factors, residence, height and weight, drinking habits, previous diseases, and occupational exposure were obtained. Ques- tions on tobacco smoke exposure at work, at home, and from current spouse were added in 1978 and revised in 1979. Information on ETS exposure was available for 25 of 37 nonsmoking male cases, 53 of 97 nonsmoking female cases, and their respective matched controls. A higher percentage of female controls than of female cases reported exposure to ETS at home (32 percent), at work (59 percent), and from spouses (60 percent). The percentages of female cases who reported exposure at home, at work, and from spouses were 30, 49, and 54 percent, respectively. None of the case-control differences in women were statistically significant. Male cases reported more frequent exposure at work (OR 3.27, p=0.045) and at home (OR 1.26), but no difference in the smoking status of their spouses (OR 1.00). The process for selecting the nonsmoking controls from the larger pool of controls in the ongoing study and for selecting the non- smoking cases and controls who were questioned with regard to ETS exposure was not described adequately. It is not clear whether the 25 of 37 male and 53 of 97 female nonsmoking cases and controls who provided information on involuntary smoking were all interviewed during or after 1978 when the questions on involuntary smoking were introduced. The proportion seemed high, since it represented 68 percent of male and 55 percent of female nonsmoking cases interviewed during the 10 years of data collection. The study was not designed to specifically address the effect of involuntary smoking, and a variable subset of questions on involuntary smoking was asked, depending on when the subjects were interviewed. Misclassifi- cation of the exposure is possible because it is not clear whether the cases and controls answered the same set of questions and whether a comparable amount of information was obtained. The researchers acknowledged the limitations of this study and presented its results as preliminary findings. 82 The Los Angeles County Study In the case-control study by Wu and colleagues (1985), 220 white female lung cancer patients (149 with adenocarcinoma and 71 with squamous cell carcinoma) and 220 population controls were individu- ally matched on sex, race, age (+5 years), and neighborhood of residence. Cases were identified from the population-based tumor registry of Los Angeles County. All cases were histologically confirmed; the histological type was based on the pathology report from the hospital of diagnosis. Using a structured questionnaire, cases and controls were directly interviewed by telephone and were asked about their own personal smoking habits and the smoking habits (amount and years of smoking) of current and former husbands, parents, and other household members during childhood and adult life. Exposure to tobacco smoke at work (in hours per day) was obtained for each job of at least 6 months’ duration. Information on medical and reproduc- tive history, heating and cooking sources, and dietary intake of vitamin A were obtained. Of 149 patients with adenocarcinoma of the lung, 29 had never smoked, nor had 2 of 71 patients with squamous cell carcinoma. The analysis of involuntary smoking was based on the 29 nonsmokers among the adenocarcinoma cases and 62 nonsmokers among the controls. A subject was classified as married to a smoker if any of her husbands had ever smoked. Similarly, a subject was considered exposed at work if she was exposed to tobacco smoke for at least 1 hour per day at any of her jobs. There were small, but nonsignifi- cantly increased risks associated with ETS exposure from spouse or spouses (OR 1.2; 95 percent C.I. 0.2, 1.7), and from coworkers (OR 1.3; 95 percent C.I. 0.5, 3.3). Increased risk was not associated with smoke exposure from either parent (OR 0.6; 95 percent C.I. 0.2, 1.7). Exposure to tobacco smoke from spouses and from coworkers was combined in an index representing smoke exposure during adult life. There was an increasing trend in risk with increasing years of exposure. The ORs were 1.0, 1.2, and 2.0 for 0, 1 to 30, and 31 or more years of involuntary smoking exposure during adult life, respective- ly, but the results were not statistically significant. Because the exposures may have occurred concurrently, the years of exposure represented units of exposure rather than calendar years of expo- sure. This study is limited by the small number of nonsmoking cases and controls. Unlike the two case-control studies that excluded adenocarcinoma or bronchioalveolar cell carcinoma (Trichopoulos et al. 1981; Correa et al. 1983), cases in this analysis were of these cell types (17 adenocarcinoma, 12 bronchioalveolar); this case mix may explain the weak association observed. 83 The Four Hospitals Study A case-control study by Garfinkel and colleagues (1985) included 134 nonsmoking female lung cancer cases selected from three hospitals in New Jersey and one in Ohio over an 11-year period, 1971-1981. Medical records served as the initial source of informa- tion on smoking status of the subject, and the nonsmoking status of each case and control was verified at interview. Three controls, colorectal cancer patients matched to cases by age (+5 years) and hospital, were interviewed for each case, giving a total of 402 controls. All diagnoses of cases and controls were pathologically confirmed. Interviewers, blinded to the diagnosis of the subjects and to the study hypothesis, administered a standard questionnaire to subjects or their next of kin. Information on the smoking habits of current spouse (total and amount smoked at home), tobacco smoke from other sources (in hours per day at home, at work, and in other settings), and exposure to tobacco smoke during childhood were obtained. Subjects were classified according to the smoking habits of current husbands. Smoking habits of a cohabitant in the same household was used for single women or those who no longer lived with their spouses. Of the cases, 57 percent were classified according to the smoking habits of husbands; the corresponding percentage in controls was not provided. Nonsmoking women living with a smoker showed an elevated risk for lung cancer (OR 1.31). The ORs for lung cancer in nonsmoking women were 1.00, 1.15, 1.08, and 2.11 when the husbands were nonsmokers, daily smokers of less than 10, 10 to 19, and 20 or more cigarettes at home, respectively (one-sided p for trend, <0.025). Similarly, a significant positive linear trend (one- sided p< 0.025) was shown when the husbands’ total amount smoked was categorized into four levels. However, there was no apparent dose-related trend by years of exposure to the husbands’ smoking (0, <20, 20-29, 30-39, 40+ years). There was no apparent association between lung cancer and tobacco smoke exposure from other sources. Cases and controls did not differ in their reported exposure to tobacco smoke during childhood or in their average hours of exposure per day to other’s tobacco smoke during the last 5 years and 25 years before diagnosis. The results remained unchanged when exposures at home, at work, and in other settings were examined separately. The odds ratios were highest for exposure in other settings, but they were based on a small number of positive responses. There was no consistent pattern by histologic type. Squamous cell carcinoma showed the strongest relationship with involuntary smoking, based on the husbands’ smoking habits at home (RR 5.0, 95 percent C.I. 1.4, 20.1), but failed to show any relationship when involuntary smoking exposure was classified by hours of daily exposure. 84 This case-control study has the largest number of nonsmoking lung cancer cases to date and provides estimates of the misclassifica- tion of disease and of the smoking status of the subjects. Among the published studies on involuntary smoking, this is the only one involving independent verification of the diagnoses of all cases. This verification showed that 13 percent of the cases classified as lung cancer were not primary cancers of the lung. This study showed that 40 percent of the women with lung cancer who had been classified as nonsmokers (or smoking not stated) on hospital records had actually smoked, compared with 9 percent of the controls. The inclusion of lung cancer patients who had actually smoked would have substan- tially increased the odds ratios with involuntary smoking, because 81 percent of the potentially misclassified cases had husbands who smoked compared with 68 percent of the “true” nonsmoking patients with lung cancer. It should be noted that none of the other studies on involuntary smoking and lung cancer based classification of smoking status solely on data from medical records. The measure of involun- tary smoking based on smoking habits of husbands attempted to differentiate between current total smoking habits and current smoking habits at home. The interview also included ETS exposure not only at home but at work and in other settings. The exposure information presented in this study is potentially limited by its extensive reliance on surrogate interviews. Owing to the need to assemble sufficient nonsmoking cases, diagnoses as early as 1971 were included, so proxies were interviewed for a high percentage of the deceased cases. Among the cases, 12 percent of the interviews were conducted with the subject, 25 percent with the husband, 36 percent with offspring, and 27 percent with an informant who had known the subject for at least 25 years. The corresponding distribution of informants in the control series was not presented. Although the ORs did not: vary consistently by respondent group, the OR for smoke exposure based on the hus- bands’ smoking tended to be lower when husbands were the respondents. Presumably, the husbands reported their own smoking habits, and it cannot be determined whether bias resulted. The information provided by surrogates may be particularly inaccurate for exposures outside the home. Systematic bias between personal and surrogate interviews and systematic bias by informant status must also be considered. Given that the topic of involuntary smoking is potentially sensitive for the family of a lung cancer patient, it is possible that some surrogates may not have provided accurate histories, particularly with regard to their own smoking habits. Surrogate respondents for cases might have been more likely to underreport exposure than those for controls; such differential reporting would have led to an underestimation of the true effect. The multiple regression analysis performed in this study did take 85 respondent status into consideration, and it was determined that this factor could not account for the relationship with husband’s smoking status (Garfinkel et al. 1985). It is not clear if the colorectal cancer controls were diagnosed in the same years as the lung cancer cases. Because the response patterns of relatives who are interviewed after the recent death of a subject may differ from responses obtained long after the subject has died, another source of bias may have been introduced. A United Kingdom Study In an ongoing hospital-based case-control study of lung cancer, chronic bronchitis, ischemic heart disease, and stroke, Lee and colleagues (1986) examined the role of involuntary smoking in a group of inpatients interviewed after 1979, when, to cover involun- tary smoking, the questionnaire was extended to married patients. An attempt was also made to interview the spouses of the married nonsmoking lung cancer patients and the spouses of the comparison group. The interview on involuntary smoking administered to hospital inpatients included questions on the smoking habits of their first spouse and on ETS exposure at home, at work, during travel, and during leisure, based on a subjective four-point scale. Spouses of nonsmokers were asked about their own smoking habits at the time of interview, during the year of admission of the subject, and during the course of their marriage. A total of 56 lung cancer cases among married lifelong nonsmok- ers was identified; 2 controls were selected for each case and individually matched on nonsmoking status, sex, marital status, age, and hospital. Among the 56 cases and 112 controls, information on spouses’ smoking habits was available for 29 (52 percent) cases and 59 (56 percent) controls from an interview conducted while the patient was still in the hospital. Interviews with spouses were obtained for 34 (61 percent) of the cases and 80 (71 percent) of the controls. Using both of these sources of information, the smoking habits of spouses were available for 47 (84 percent) of the cases and 96 (86 percent) of the controls. Nine risk estimates were presented for spouses’ smoking, for each of the three sources of information (subject, spouse, and both), for men and women separately and for both sexes combined. The researchers concluded that spousal smoking was not associated with lung cancer, because risks were not consistently elevated. When their spouses reported about their own smoking, a RR of 1.60 (95 percent C.I. 0.44, 5.78) was found for lung cancer in the women. In contrast, a RR of 0.75 (95 percent C.I. 0.24, 2.40) was found when the female subjects reported about the smoking habits of their spouses. On the other hand, a RR of 1.01 (95 percent C.I. 0.23, 4.41) was found for male lung cancer patients when 86 their spouses reported about their own smoking, whereas the risk was 1.53 (95 percent C.I. 0.37, 6.34) when the male patients evaluated their spouses’ smoking habits. As might be expected, the combined risk in relation to spouses’ smoking for both sexes and both sources of information was near unity, at 1.11 (95 percent C.I. 0.59, 2.39). Using a second group of controls, presumably all of the nonsmokers who had responded to the hospital inpatient interview on involun- tary smoking, the researchers reported no significant case and control differences in exposure to ETS at home, at work, during travel or leisure, from spouses, or for all sources combined. This study has several limitations that must be considered in interpreting its results. Although the study attempted to verify involuntary smoking from spouses by using two sources of informa- tion, dual reports were obtained for only 16 (29 percent) of the cases and 48 (38 percent) of the controls. The questions on involuntary smoking included exposure from other sources, but they were based on a subjective scale, and different groups of controls were used for the analyses. Information was not presented on the accuracy of the diagnosis of lung cancer or on the histological types included in the study. Moreover, the investigators did not verify the smoking status of the subjects during the interviews with spouses. The study’s inconsistent findings by source of information and by sex may reflect the absence of an association between involuntary smoking and lung cancer in this population, or may reflect method- ological problems in the design or conduct of the study. The main study was not originally designed to investigate the effects of involuntary smoking. However, because of interest in this issue, the investigators decided to “increase the number of interviews of married lung cancer cases and controls.” The representativeness of the cases and the controls cannot be determined because there may have been differential selection factors in enrolling nonsmoking lung cancer cases and controls into the study; thus, selection bias cannot be ruled out. The method for selecting the 112 nonsmoking controls was not adequately described in the report; it is not clear whether they were selected from the pool of all controls for lung cancer or from the pool of controls for the four diseases under study. There is also an apparent discrepancy in the number of nonsmoking cases cited in the text and presented in the results. The report cited 44 never smokers among a total of 792 lung cancer patients who completed the involuntary smoking questionnaires when they were in the hospital. However, the analysis for an involuntary smoking effect based on interviews with subjects in the hospital showed only 29 lung cancer patients. This discrepancy was not explained. The risks in relation to smoking by spouses varied with the source of information. The risk estimates tended to be higher when the respondents were men, either reporting about their own smoking 87 habits or the smoking habits of their spouses. This pattern could result if the male respondents overestimated exposure to environ- mental tobacco smoke or if the female respondents underestimated exposure. An analysis of the patients (16 cases and 43 controls) for whom data were provided by the spouses and by the subjects themselves showed a 97 percent concordance for spouses’ smoking during the year of the interview and 85 percent concordance for spouses’ smoking some time during the marriage. Lack of specificity in the question asked regarding spouses’ smoking any time during the marriage may partly explain the discrepancy in response. To the extent that there is no consistent pattern in the direction of this discrepancy, it can be assumed that a spouse was a smoker sometime during the marriage if either respondent answered positively. On the basis of this assumption, RRs of 1.47 (spouses of 4 of 7 cases and 7 of 18 male controls smoked) and 1.39 (spouses of 8 of 9 female cases and 16 of 25 female controls) were found for the men and the women, respectively, in relation to their spouses’ smoking. The risk estimates were not statistically significant, but the number of subjects was small. The Japanese Case-Control Study The study by Akiba and colleagues (1986) included 428 (264 men, 164 women) incident primary lung cancer cases diagnosed between 1971 and 1980 in a cohort of 110,000 Hiroshima and Nagasaki atomic bomb survivors. Controls were selected among cohort members who did not have cancer. For deceased cases, corresponding controls were selected from among cohort members who died of causes other than cancer or chronic respiratory disease. The controls were individually matched to cases on a number of factors, including age, sex, birth year (+2 years), city of residence, and vital status; a variable number of controls was interviewed, depending on the place of residence. Of the lung cancers, 29 percent were pathologically confirmed, 43 percent were radiologically or clinically diagnosed, and the remain- der were found at autopsy. Subjects or their next of kin were interviewed regarding the subjects’ personal smoking, smoking habits of current spouses and parents, and occupation. Less than 10 percent of the interviews with the men and about 20 percent of the interviews with the women were conducted with the subjects themselves. The distributions of the next of kin interviewed were similar for the cases and the controls. Among the cases, 103 (19 men, 84 women) had never smoked, compared with 380 controls (110 men, 270 women). An elevated lung cancer risk associated with smoking habits of spouses was observed for men and women. An OR of 1.8 (95 percent C.I. 0.5, 5.6) was found for nonsmoking men married to-wives who smoked and an OR of 1.5 88 (95 percent C.I. 1.0, 2.5) for nonsmoking women married to husbands who smoked. Lung cancer risk increased with the amount smoked per day by the husband, with an OR of 2.1 for women whose husbands smoked 30 or more cigarettes per day. The OR was higher (1.8) among women who had been exposed within the past 10 years compared with those who had been exposed before that time (OR 1.3). However, an increasing duration of exposure to husbands’ smoking was not associated with a monotonic trend of increasing risk. The relation between lung cancer and husbands’ smoking was observed regardless of the occupation of wives (housewife, white- collar, blue-collar), but the highest odds ratio was for women who worked in blue-collar jobs and whose husbands were heavy smokers (OR 3.2). Despite a high proportion of proxy interviews, the distribution of informant type was comparable for cases and controls; this compara- bility minimizes the possibility of recall bias. The high concordance between the subjects’ reported smoking status in a previous survey and the information from the next of kin is reassuring. Although a high proportion of cases had no histological confirmation, an increased risk was observed regardless of the method of diagnosis. This study also provided an opportunity to test for potential confounding factors, including radiation exposure and occupation, but none were identified. The Swedish Study The study by Pershagen and associates (in press) included 67 incidents of primary lung cancer cases from a cohort of 27,409 nonsmoking Swedish women who were participants in a national census survey or in a twin registry. Two controls were selected from each source and were matched to cases on year of birth, and on vital status if they were selected from the twin registry. Subjects or their next of kin (excluding husbands) were mailed a questionnaire that assessed their exposure to tobacco smoke from parents and the husband with whom the subject had lived the longest time. Information on residential and occupational history was also obtained. Elevated lung cancer risk associated with the smoking habits of spouses was observed. For all lung cancers, ORs of 1.0, 1.0, and 3.2 were observed for women who had no, low (<15 cigarettes/day or <1 pack of pipe tobacco/week or <30 years of marriage), and high exposure to their husbands’ smoking, respectively. The increased risk was found primarily for squamous and small cell carcinomas (OR 3.3); consistent effects could not be detected for other histologic types. On the basis of the approximately 75 percent of respondents who provided information on parental smoking, there was no effect 89 of parental smoking on risk for all lung cancers, after controlling for the husbands’ smoking. The study is similar in design to the Japanese case-control study (Akiba et al. 1986), except that the Swedish investigators obtained histologic confirmation for all of the cases under study. Moreover, this study excluded husbands as informants, so a potential bias associated with husbands’ reporting their own smoking habits could be eliminated. The investigators contended that the finding of an association only for squamous cell and small cell carcinomas argues against a spurious finding because it is unlikely that the next-of-kin informers would have been aware of the histologic types diagnosed in the cases. The German Study The last in this description of studies to date based on the case- control design is a German study (Knoth et al. 1983), interpreted by the investigators as showing a role for involuntary smoking in the etiology of lung cancer. Of 39 nonsmoking women with lung cancer, 24 (62 percent) had lived with smokers. Although a comparison group was not interviewed, the investigators surmised that this frequency of smokers in the household was about three times higher than expected from census-based smoking statistics for men in the age group 50 to 69. The limitations of this study are evident; the researchers assumed that smoking prevalences for men were indica- tive of smoking prevalences for members of the cases’ households and a specific control series was not enrolled. Other Sources of Tobacco Smoke Exposure Parental Smoking Recently evaluated as a risk factor for lung cancer, parental smoking is of interest because of the large number of exposed children, the age at which it begins, and its duration. Results of this association are variable, demonstrating no association, association with just mothers’ smoking, or association with both mothers’ and fathers’ smoking. Correa and colleagues (1983) reported an associa- tion between lung cancer risk and the mothers’ smoking in the men, which persisted after adjusting for personal smoking habits (OR 1.5, p<0.01). This association was not observed in the women, and increased risk was not related to fathers’ smoking in either the men or the women. A positive association between the mother’s smoking and lung cancer risk was reported in a study of female lung cancer, but the result was not statistically significant after adjusting for personal smoking habits (OR 1.7, 95 percent C.I. 0.8, 3.5) (Wu et al. 1985). Another study suggested that the father’s smoking (OR 2.5) and the mother’s smoking (OR 1.8) were each related to increased 90 lung cancer risk after adjusting for age and individual smoking habits (Sandler, Wilcox, Everson 1985b). These results were based on small numbers, however, particularly for the mother’s smoking (in 2 of 15 cases, the mother smoked). Significant associations with maternal or paternal smoking were not found in two other studies (Akiba et al. 1986; Pershagen et al. in press); however, information was lacking for about one-third of the subjects. Since smoking habits of children are highly correlated with smoking habits of parents, it is difficult, even after adjusting for personal smoking habits, to be certain that an independent effect of parental smoking has been observed. None of the studies with data on parental smoking had sufficient numbers to examine the effects of parental smoking on nonsmokers. In Louisiana, one nonsmoking case had a mother who smoked (Correa et al. 1983). In Hong Kong, 6 percent (5/88) of the nonsmoking cases reported that their parents smoked compared with 2 percent (3/137) of the nonsmoking controls (Koo et al. 1984). In Los Angeles, the frequencies of smoking by mothers and fathers were lower for nonsmoking cases (4 percent mothers, 28 percent fathers) than for nonsmoking controls (11 percent mothers, 35 percent fathers) (Wu et al. 1985). Exposure to tobacco products during childhood was not significantly different between cases and controls (OR 0.91, 95 percent C.I. 0.74, 1.12) in another study (Garfinkel et al. 1985). It is difficult to obtain accurate information regarding remote childhood events, so data on parental smoking tend to be crude or unavailable. Information on maternal smoking during pregnancy would not be available unless the parents could be interviewed. Because lung cancer occurs most often among older persons, an interview with a parent will generally be impossible. Moreover, information on parental smoking will most likely be unavailable or meaningless if surrogate interviews are conducted. Coworker’s Smoking The workplace, an important source of tobacco smoke exposure, was not considered in the early studies on involuntary smoking. Later case-control studies provided some information on tobacco exposure at work, but the data were limited and inconclusive. Kabat and Wynder (1984) reported a statistically significant positive association between tobacco smoke exposure at work for men but not for women. In comparison with controls, patients with cancer in Hong Kong reported more hours and years of exposure at the workplace, but only two cases and four controls had exposure to tobacco smoke at work (Koo et al. 1984). Data in the Los Angeles study suggested that the workplace may be an important source of exposure to tobacco smoke. A small increased risk was observed for 91 any exposure at work, and an index combining exposure from coworkers and spouse or spouses indicated a trend of increasing risk with increasing exposure (Wu et al. 1985). Garfinkel and colleagues (1985) found no differences between cases and controls in their exposure to tobacco smoke at work during either the 5 years or the 25 years before diagnosis, and a similar lack of an association was also reported by Lee and colleagues (1986). Dose-Response Relationship An important factor in the appraisal of the relationship between involuntary smoking and lung cancer is the assessment of dose— response relationships. However, this analysis hinges on the defini- tion of exposure. Data on active smoking and lung cancer suggest that exposure measures considering amount, duration, and recency of exposure should be employed in examining dose-response rela- tionships in active smokers (Doll and Peto 1978; Pathak et al. 1986). Misclassification of exposure to ETS may be expected when exposure categorization is based on the amount or the duration of smoking by the current spouse or cohabitant, as current exposure from one source may not adequately measure past exposure or cumulative exposure. Moreover, these exposure variables may not be indicative of the exposure dose to the respiratory tract because dose determi- nants such as ventilation rates, breathing pattern, and deposition factors are unaccounted for. Research is now being directed toward the integration of informa- tion from questionnaire responses, biochemical studies, and environ- mental sampling to determine the most accurate measures of exposure to the respiratory tract. However, exposure assessments for epidemiological studies of lung cancer and involuntary smoking will remain limited by the inaccurate recall of exposures that occurred as much as 40 to 50 years earlier. Nevertheless, research on exposure should resolve several points of uncertainty. The comparability between exposure dose measured by amount smoked and by hours or years of smoking should be assessed. The relative importance of sources of ETS should also be clarified, so there will be some agreement on whether cumulative dose should differentiate between sources of exposure. In the absence of data showing a particular exposure measure to be optimal, an index of involuntary smoking based on the amount smoked by spouses shows the most consistent dose-response relation- ship with lung cancer risk (Hirayama 1981a; Trichopoulos et al. 1981; Correa et al. 1983; Garfinkel et al. 1985; Akiba et al. 1986). Other indices of involuntary smoking exposure have not been as well studied and have not shown a consistent dose-response relationship with lung cancer risk. These exposure variables included total years of exposure to spouses’ smoking, average daily hours of exposure 92 from all sources, and cumulative lifetime hours and years of exposure. Among the studies that have found a dose-response relationship with amount smoked by a spouse, three have also examined the relationship by duration of spouse’s smoking (Correa et al. 1983; Garfinkel et al. 1985; Akiba et al. 1986), but only one study showed similarly increased risk using a dose and duration variable (Correa et al. 1983). In the study by Garfinkel and coworkers (1985), only years of smoking by the current husband or cohabitant was asked; therefore, differences in the duration of living with current husband or cohabitant may account for the less consistent dose-response relationship. In their Japanese case-control study, Akiba and colleagues (1986) suggest that intensity (amount smoked per day and recency of exposure) may be the key index of ETS in studies of lung cancer risk. Two studies have assessed total involuntary smoking exposure to ETS. The method used by Koo and coworkers (1984) relied on respondents to describe the exposures from each source separately, and a summary measure of exposure was derived by the investiga- tors. The method used by Garfinkel and coworkers (1985) relied on the respondents to average their exposures from all sources for specific time periods. The method of Koo and coworkers (1984) may not have adequately considered intensity of exposure; therefore, an association may have been obscured by combining low and high intensity exposures as if they were equally important. In the study by Garfinkel and coworkers (1985), a high percentage of case interviews and, presumably, control interviews was conducted with surrogates. Although information provided by surrogates regarding demographic variables is generally valid, as are responses on cigarette smoking status (current, prior, never), more detailed information on the cigarette smoking of a deceased spouse has more limited validity (Lerchen and Samet 1986). Surrogate interviews may provide adequate information about tobacco smoke exposure at home, but may be inaccurate for describing gradients of total tobacco smoke exposure from all sources. Expected Lung Cancer Risk An extensive data base describes the relationship between active smoking and lung cancer (US DHEW 1979, US DHHS 1982; IARC 1986). This information has been utilized to construct mathematical models to describe the relationship of dose, duration, initiation, and cessation of active smoking for risk of lung cancer. For several reasons, comparable models have not yet been developed for involuntary smoking and lung cancer. First, research on involuntary smoking and lung cancer is recent. Second, involuntary smoking is not as readily quantified as active smoking; tobacco smoke is 93 ubiquitous in the environment and present in variable but generally low concentrations in comparison with MS, and inhaled dose varies with ventilation and other physiological factors (Hiller 1984; Hoegg 1972; Hoffmann et al. 1984; Schmeltz et al. 1975; Stober 1984; us DHHS 1984). Nevertheless, theoretical models, originally developed to describe the relationship of active smoking and lung cancer, have been used to predict lung cancer risk from involuntary smoking. Using Doll: and Peto’s (1978) model [(0.273 x 102) (cigarette/day + 6)? (age 22.5)45] for active smoking and lung cancer, Vutuc (1984) calculated expected lung cancer risks for various exposure levels, ranging from 0.1 to 5.0 cigarettes per day. For exposure levels of 0.1, 1.0, 2.0, and’ 5.0 cigarettes per day, the corresponding risk estimates were 1.03, 1.38, 1.78, and 3.36, respectively. These low-doge active smoking risk estimates are comparisons of active smokers with all nonsmokers (those with high ETS exposure and those with low ETS exposure). The risk estimates in involuntary smoking studies are a comparison of nonsmokers with higker levels of involuntary smoking exposure with nonsmokers who have lower levels of involuntary smoking exposure. As a result, the numerical values of the risk estimates in active smoking studies are not directly comparable to those in the involuntary smoking studies. The appropriateness of extrapolating from the active smoking model hinges on the actual exposure of a nonsmoker. Estimates of exposure have been derived from various sources. Experimental conditions have been used to quantify the involuntary smoker's exposure to ETS. Hugod and colleagues (1978) reported that under conditions heavily polluted with sidestream smoke (to maintain a carbon monoxide concentration of 20 ppm), the particulates of tobacco smoke inhaled by involuntary smokers was small, the equivalent of one-half to one cigarette per day. Exposures may also be estimated from biochemical measurements. Studies comparing cotinine levels in nonsmokers and smokers show cotinine levels in nonsmokers that correspond to about one-sixth to one-third of a cigarette per day (Jarvis et al. 1984; Wald et al. 1984). Higher cotinine levels in nonsmokers, comparable to about two cigarettes per day, have been reported (Matsukura et al. 1984, 1985), but the results were questioned (Adlkofer et al. 1985; Pittenger 1985) and await confirmation. The epidemiologic evidence on the lung cancer risk associated with marriage of a nonsmoker to a smoker has been criticized as implausible on the basis of predictions from Doll and Peto’s model (Lee 1982a,b; Vutuc 1984). It has been argued that relative risks of 2 or 3 from involuntary smoking correspond to active smoking of two to five cigarettes per day and that this equivalent level of active smoking is too large to be realistic. This argument fails to consider 94 the difference in the comparison groups used to generate the risk estimates in studies of active smoking and involuntary smoking. The risk estimates for studies of active smoking use as a comparison group all nonsmokers, which includes those with and without high levels of exposure to ETS. Studies of involuntary smoking use risk estimates that are derived by comparing nonsmokers with higher levels of exposure to ETS with nonsmokers with lower levels of exposure to ETS. Because the risk estimates in active and involun- tary smoking studies use different comparison groups, the numerical values are not directly comparable. In order to make them comparable, the risk estimates in involun- tary smoking and active smoking studies would have to be calculated using the same reference group. If the reference population used is all nonsmokers, then the risk estimates for nonsmokers married to nonsmokers are reduced to below 1 (Le., their lung cancer risk would be lower than the risk for all nonsmokers as a group). The risk estimates for nonsmokers married to smokers would be above 1 (i.e., would be greater than the risk for all nonsmokers as a group), but the numerical value of the risk estimate would be reduced from th value obtained by comparison with nonexposed nonsmokers. If the data from the Japanese cohort study (Hirayama 1981la) ar recalculated to use all nonsmokers as the reference population, the risk estimate for lung cancer in nonsmoking wives of nonsmoking husbands would be 0.63 and the risk estimate for nonsmoking women married to smokers (current or former) would be 1.12. The value of 1.12 compares the risk for nonsmoking wives of smoking husbands with the risk for all nonsmokers in the studies of active smoking. This magnitude of risk is within the range of risk that would be predicted using the Doll and Peto (1978) model for calculating active smoking risk for smokers of 0.1 (risk estimate 1.03) and 1 (risk estimate 1.38) cigarette per day. The evidence for exposure to environmental tobacco smoke based on biologic markers of tobacco smoke exposure indicate that involuntary smoking exposure results in levels of biologic markers (e.g., cotinine) that are similar to levels expected in smokers of 0.1 to 1 cigarette per day. Thus, estimates derived using similar comparison groups suggest that the lung cancer mortality experience due to involuntary smoking is similar to that which would have been expected from an extension of the dose-response data for active smoking to involun- tary smoking exposures. An alternative method of estimating expected lung cancer rates has been proposed by Repace and Lowrey (1985). They compared the age-standardized lung cancer mortality rates of Seventh-Day Ad- ventists (SDAs) who had never smoked with a demographically comparable group of nonsmoking non-SDAs and attributed the difference in lung cancer deaths solely to involuntary smoking. This 95 analysis was based on the following assumptions: (1) that SDAs had no exposure to passive smoking, whereas all of the non-SDAs were exposed, (2) that men and women had equal lung cancer death rates, and (3) that there were no other differences between the two groups. Summary Previous Reports of the Surgeon General have reviewed the data establishing active cigarette smoking as the major cause of lung cancer. The absence of a threshold for respiratory carcinogenesis in active smoking, the presence of the same carcinogens in mainstream smoke and sidestream smoke, the demonstrated uptake of tobacco smoke constituents by involuntary smokers, and the demonstration of an increased lung cancer risk in some populations with exposures to ETS leads to the conclusion that involuntary smoking is a cause of lung cancer. The quantification of the risk associated with involuntary smoking for the U.S. population is dependent on a number of factors for which only a limited amount of data are currently available. The first of these factors is the absolute magnitude of the lung cancer risk associated with involuntary smoking. As was previously described, the studies that have been performed to assess the lung cancer risk of involuntary smoking do not contain a zero-exposure group. Some exposure to tobacco smoke is essentially a universal experience; therefore, studies of involuntary smoking compare & low-exposure group with a high-exposure group. The magnitude of the risk estimate obtained is a function of the increase in risk produced by the difference in tobacco smoke exposure between the two groups examined, rather than an absolute measure of the risk of exposure in comparison with no exposure. The magnitude of the difference in tobacco smoke exposure between groups identified by spousal smoking habits may vary from study to study; this variation may partially explain the differences in risk estimates among the studies. would therefore require a better understanding of the magnitude of the exposure to environmental tobacco smoke that occurs in the populations examined in the studies of involuntary smoking and lung cancer. Of particular interest is the magnitude of the difference in exposure between the high-exposure group and the low-exposure group. A second set of data that would be needed to estimate the risk for the U.S. population is the dose and distribution of exposure to BTS in the population. The studies that have been performed have attempt- ed to identify groups with different exposures, but little is known about the magnitude of the exposures that occur in different segments of the U.S. population or about the variability of exposure with time of day or season of the year. The changing norms about 96 smoking in public and the changing prevalence of active smoking during this century suggest that ETS exposure may have varied substantially over this century. A better understanding of the exposures that are actually occurring in the United States, and of past exposures, would be needed to accurately assess the risk for the U.S. population. The epidemiological evidence that involuntary smoking can signif- icantly increase the risk of lung cancer in nonsmokers is compelling when considered as an examination of low-dose exposure to a known carcinogen (i.e., tobacco smoke). Eleven of the thirteen epidemiologi- cal studies to date show a modest (10 to 300 percent) elevation of the risk of lung cancer among nonsmokers exposed to involuntary smoking; in six studies positive associations were statistically significant. The studies showing no or nonsignificantly positive findings were generally the weakest in terms of sample size (Gillis et al. 1984; Chan and Fung 1982; Koo et al. 1984; Kabat and Wynder 1984; Wu et al. 1985; Lee et al. 1986), study design (Kabat and Wynder 1984; Lee et al. 1986), or quality of data (Chan and Fung 1982). In Table 10 are shown the sources and types of bias, and in Table 11, the statistical power, of the various case-control studies (Schles- selman 1982). On the basis of the observed relative risks reported in the studies, the respective exposure fraction in the contro] popula- tions, and an a=0.05 for a two-sided significance test, only the studies by Trichopoulos and colleagues (1983) and Correa and colleagues (1983) have a probability of above 80 percent of finding a statistically significant result, whereas the majority of the case- — control studies show a study power of about 0.10 to 0.20. The power of the study, as expected, improves when a one-sided significance test is considered. Among the studies in which information on involun- tary smoking was available to conduct a trend test for dose, the power for detecting the observed trend was above 50 percent for five of the studies. However, the power for a two-sided test and a one- sided test, based on observed relative risk, and the power for a one- sided trend test, based on observed results, are difficult to interpret because the power is a function both of design aspects (sample size, case-control ratio, exposure prevalence) and of the observed relative risk. To focus on comparisons of the design differences between studies, the power estimates for a fixed relative risk of 2 show that five of the studies would have a power of 0.75 or greater to detect a statistically significant result. Thus, it is not surprising that some studies failed to achieve statistical significance, but the lack of statistical significance in all studies should not invalidate the positive significant associations for involuntary smoking that have been observed. 97 TABLE 10.—Sources and types of bias in case-control studies Misclassification Author’a Misclassification of passive smoke Interviewer Respondent Study conclusion of lung cancer exposure bias bias Trichopoulos Positive +) + (4) + (ft) _ et al, (1983) Correa et al. Positive _ +()) - _ (1983) Chan and Fung Negative _ +(] or ft) ? ? (1982) Koo et al. Negative _- + (J) or f) ? ? (1984) Kabat and Wynder Negative _ +(} or ft) ? ? (1984) Wu et al. Weak (1985) positive —_ + (4) —_ Garfinkel et al. Positive - +(J or f) - +() or f) (1985) Akiba et al. Positive . + (4) + (1) ? +({ or t) (1986) Pershagen et al. Positive _ +({ or f) - ~~ (in presa) NOTE: Probability of misclassification: + = likely; — = not likely;? = cannot be determined. Effect on observed risk: | = overestimated risk as reault of bias; | = underestimated risk as result of bias. Six epidemiological studies found statistically significant in- creased risks associated with spouse’s smoking; all demonstrated a dose-response relationship, and several suggested a stronger associa- tion with squamous cell and small cell carcinoma than with other cell types. Three of these studies (Hirayama 1984a; Correa et al. 1983; Akiba et al. 1986) included nonsmoking male lung cancer patients, and the complementary findings in nonsmoking husbands married to smoking wives strengthen the evidence on involuntary smoking. The four studies with significant positive findings pub- lished since 1981 (Correa et al. 1983; Garfinkel et al. 1985; Akiba et al. 1986; Pershagen et al., in press) not only corroborated the findings of Hirayama (198la) and Trichopoulos and colleagues (1981), but answered the many criticisms directed at these two studies. 98 TABLE 11.—Study power for case-control study based on an unmatched analysis Observed relative Power for Power for Power for Power for Proportion of risk for ever vs. two-sided test one-sided test one-sided trend one-sided test Number Control: controls’ spouses never exposed to based on based on test based on based on RR=2 for Study of cases case ratio who smoked spouses’ smoking observed RR observed RR observed results' ever vs. never exposed Trichopoulos et al. 17 2.92 0.62 ~ 2.11 0.79 0.87 0.88 0.88 (1983) Correa et al. 30 10.43 0.28 2.97 0.83 0.88 0.97 0.55 (1983) Chan and Fung 84 1.66 0.48 0.75 0.17 0.26 NA? 0.80 (1982) Koo et al. 88 1.56 0.713 1.23 0.10 0.17 0.10 0.64 (1984) Kabat and Wynder* 36 1.03 0.54 0.85 0.05 0.10 NA* 0.39 (1984) Wu et al.® 28 1.96 0.60 141 0.10 0.17 0.16 0.37 (1985) Garfinkel et al. 134 3.00 0.61 1.23 0,24 0.36 0.71 0.94 (1985) Lee et al. 47 2.04 0.62 11 0.04 0.08 NA! 0.52 (1986) . Akiba et al. 84 2.96 0.67 1.47 0.26 0.38 0.53 0.75 (1986) OOT TABLE 11,.—Continued Observed relative Power for Power for Power for Power for Proportion of risk for ever ve, two-sided test one-sided test one-sided trend one-sided test Number Control: controls’ spouses never exposed to based on based on test based on based on RR=2 for Study of cases case ratio who smoked spouses’ smoking observed RR observed RR observed results' ever vs. never exposed Pershagen et al. 67 6.18 0.44 1.23 0.12 0.19 0.46" 0.83 (in press) Pooled * 676 2.96 0.52 153 0.99 1.00 NA 1,00 Pooled® 509 3.40 0.52 1.88 1.00 1.00 1.00 1.00 1 Based on three levels of passive smoke exposure as defined in respective studies. * Data not available for trend test. 7 Includes spouses, cohabitants, and coworkers who smoked. * Based on nonsmoking cases and controls with information on spouses’ smoking. 5 Based on cases and controls who were ever married. ® Based on female cases and controls with information on husbands’ smoking (number of cigarettes smoked per day). ‘Estimate based on 26 cases and 151 controls in the low exposure category, 7 cases and 12 controls in the high exposure category. * Based on combined results of the 10 case-control studies. * Based on combined results of the seven case-control studies with data available for trend test. The most serious criticism is the misclassification of the active smoking status of the subjects, which can produce an apparent increased risk with involuntary smoking. Moreover, it is likely to result in differential misclassification because spouses tend to have similar smoking habits (Burch 1981; Sutton 1981; Higgins et al. 1967). Speculation that the positive results reported in Japan and Greece were due to cultural bias against the admission of smoking by women in these more traditional societies may be discounted because positive significant findings have now been observed in the United States (Correa et al. 1983; Garfinkel et al. 1985) and in Sweden (Pershagen et al., in press), where no comparable social stigma exists. Moreover, in the studies by Garfinkel and coworkers (1985) and Pershagen and coworkers (in press), the personal smoking status of each subject was validated and verified at interview, usually by next of kin, who presumably would have no reason to misrepresent the true smoking status of the subject. Misclassification of the lung as the primary site and the lack of pathological confirmation are repeated concerns, but it must be stressed that this bias would tend to dilute a true effect. Correa (1983), Garfinkel (1985), and Pershagen (in press) and their respec- tive colleagues addressed this issue by including only pathologically confirmed lung cancers and considering histological cell type in their analyses. In the study by Garfinkel and associates (1985), after an independent pathological review was conducted, a significant associ- ation of excess risk with involuntary smoking remained. Misclassifi- cation of exposure to ETS cannot be dismissed, since an index based solely on the smoking habits of a current spouse may not be indicative of past exposure, cumulative exposure, or the relevant dose to the respiratory tract. The magnitude of risk associated with involuntary smoking exposure is uncertain. Relative risks ranging from 2 to 3 were generally reported for the highest level of exposure based on the spouses’ smoking habits, but since sample sizes in most studies are not large, the point estimates of effect are unstable, and confidence limits are broad and generally overlap from one study to another. An index of involuntary smoking based on the smoking habits of the spouse is a simplistic and convenient measure. There is no reason to believe, however, that the excess risk associated with involuntary smoking is restricted to exposure from spouses. Nonsmokers married to smokers are likely to be more tolerant of ETS exposure and to experience more exposure to environmental tobacco smoke (Wald and Ritchie 1984). Higher risk estimates for involuntary smoking have been obtained in studies restricted to squamous cell and small cell carcinomas of the lung. Although involuntary smoking can be established as a cause of lung cancer, important questions related to this exposure require 101 further research. More accurate estimates for the assessment of exposure in the home, workplace, and other environments are needed. Studies of sufficiently large populations should also be performed. New data from such studies should yield more certain risk estimates and describe the magnitude of the lung cancer risk in nonsmokers. Other Cancers Several recent studies provide data on the relationship of ETS exposure to cancer at sites other than the lung. Two published reports address the risk of other cancers in adults from exposure to tobacco smoke from spouses. Using the same Japanese cohort described previously, Hirayama (1984a) reported excess mortality for cancers of the paranasal sinus (N=28) and brain (N=34) among nonsmoking women who were married to smokers. The standardized mortality ratios (SMRs) for nasal sinus cancer were 1.00, 1.67, 2.02, and 2.55 for women whose husbands never smoked, or had smoked 10 to 14, 15 to 19, or 20 or more cigarettes per day, respectively (one- sided p for trend, 0.03). The corresponding SMRs for brain tumors were 1.00, 3.03, 6.25, and 4.32, respectively (one-sided p for trend, 0.004). The total number of deaths due to nasal cancer and brain tumors was small, and the numerators in the risk calculations were unstable, based on five nasal cancers and three brain cancers in women whose husbands were nonsmokers. In one study (Brinton et al. 1984), active tobacco smoking was associated with an increased risk of sinus cancer, particularly squamous cell tumors. Sidestream smoke has also been suggested to be of etiological importance in brain tumors in children (Preston-Martin et al. 1982). In a case-control study of adult cancers in relation to childhood and adult exposure to involuntary smoking, Sandler and coworkers (1985a, 1986) reported an overall cancer risk of 1.6 (95 percent CL. 1.2, 2.1) associated with exposure to spouses’ smoking, which was more marked in nonsmokers than smokers. Significant increases were observed for cancer of the breast (OR 1.8), cervix (OR 1.8), and endocrine organs (OR 3.2). This study has been criticized in its choice of controls and in the exclusion of certain cancers by the design of the study. The biological plausibility of the study’s findings was also questioned because the highest risk estimates were observed for cancers that have not been consistently related to active smoking and because higher risks were observed for nonsmokers than for smokers. Failure to control for potential confounding factors and known risk factors for the individual cancer sites under study may have produced artifactual results (Friedman 1986; Mantel 1986; Burch 1986). In a subsequent analysis of the same study population, Sandler, Wilcox, and Everson (1985a,b) reported increasing cancer 102 risks with increasing exposure to involuntary smoking as measured by the number of smokers in the household and by the time periods of exposure. The biologic plausibility of these findings was also questioned (Burch 1985; Higgins 1985; Lee 1985). The effect of parental smoking on the development of cancers both during childhood and in adult life is also of interest. The relationship of parental smoking to overall cancer risk in children or in adults has been assessed in three studies. A prospective survey (Neutel and Buck 1971) of about 90,000 infants in Canada and the United Kingdom followed for a maximum of 10 years found an overall cancer risk of 1.3 (95 percent C.I. 0.8, 2.2) associated with maternal smoking during pregnancy. No dose-response relationship was observed, but there were few heavy smokers (>1 pack/day) in this study. A Swedish case-control study (Stjernfeldt et al. 1986) of all cancers found a risk of 1.4 (95 percent C.I. 1.0, 1.9) for maternal smoking during pregnancy. A dose-response relationship was dem- onstrated; the risk was highest in the most exposed group, those smoking 10 or more cigarettes per day (RR 1.6, p< 0.01). On the basis of the smoking habits of the parents of subjects up to 10 years of age, Sandler, Everson, Wilcox, and Browder (1985) reported no significant difference between all cancer cases and controls with respect to the mother’s smoking (RR 1.1, 95 percent C.L. 0.7, 1.6), but the father’s smoking was related to an overall increased risk (RR 1.5, 95 percent C.l. 1.1, 2.0). In these three studies, analysis by specific cancer site revealed an increased risk of leukemia associated with parental smoking. Neutel and Buck (1971) found an almost twofold increased risk of leukemia in children of mothers who smoked during pregnancy, but the association was not statistically significant. Stjernfeldt and colleagues (1986) reported a significant positive association between maternal smoking and acute lymphoblastic leukemia. The relative risks were 1.0, 1.3, and 2.1 (p for trend, <0.01) for mothers who smoked 0, 1 to 9, and 10 or more cigarettes per day, respectively. Similar significant positive associations with maternal smoking were not observed for other cancer sites, but the risk assessments were based on a small number of cases. This study suggests that the relationship between maternal smoking and leukemia was strongest for smoking during the 5-year period before pregnancy, intermediate for smoking during pregnancy, and lowest for smoking after pregnancy. In the study by Sandler, Everson, Wilcox, and Browder (1985), the mother’s smoking and the father’s smoking were sepa- rately and jointly associated with an increased risk for leukemia and lymphoma. The relative risk was 1.7 when one parent smoked and 4.6 when both parents smoked (p for trend, <0.001). The increased risk with parental smoking was observed regardless of the personal smoking status of the subject. No other cancer site was associated 103 with the mother’s smoking, although the father’s smoking was associated with increased risks for other cancer sites, including the brain and the cervix. Two studies of leukemia in children found no relationship with parental smoking (Manning and Carroll 1957; Van Steensel-Moll et al. 1985). In the study by Manning and Carroll (1957), the mothers’ general smoking habits were assessed, whereas Van Steensel-Moll and colleagues (1985) obtained information on the smoking habits of both parents in the year before the pregnancy. Stewart and colleagues (1958) reported a statistically significant risk of 1.1 (p=0.04) for leukemia in association with the mothers’ smoking, but cautioned that the smoking information on the mothers pertained to their habits at the time of interview, which took place after the deaths of the patients and may have been affected by bereavement. The effect of parental smoking habits has been examined in epidemiological studies of brain tumors, rhabdomyosarcoma, and testicular cancer in children. Gold and colleagues (1979) reported an association between maternal smoking prior to and during pregnan- cy and brain tumors in children. A relative risk of 5.0 (p=0.22) was found, but the result was based on a small number of patients and was not statistically significant. No relationship between maternal smoking during pregnancy (RR 1.1, one-sided p=0.42) and brain tumors in children was found in another study (Preston-Martin et al. 1982), but a significantly increased risk (RR 1.5, one-sided p=0.03) associated with mothers living with a smoker (usually the child’s father) during pregnancy was observed. A significantly increased risk with the father’s smoking, but not the mother’s smoking was also reported in a study of rhabdomyosarcoma (Grufferman et al. 1982). The father’s smoking conferred a significant increase in risk (RR 3.9, 95 percent C.I. 1.3, 9.6), but the mother’s smoking during and after the pregnancy was not significantly different between cases and controls (RR 0.8, 95 percent C.I. 0.3, 2.0). A history of maternal smoking during pregnancy did not differ for testicular cancer cases and controls (RR 1.0, p=0.57) in one study (Henderson et al. 1979). There are at present insufficient data to adequately evaluate the role of involuntary smoking in adult cancers other than primary carcinoma of the lung. In addition, active smokers necessarily receive greater exposure to ETS than nonsmokers. Thus, effects would not be anticipated in involuntary smokers that do not occur in active smokers (IARC 1986), and the biological plausibility of associations between ETS exposure and cancer of sites not associated with active smoking must be questioned. The findings of Hirayama (1984a) and Sandler, Everson, and Wilcox (1985) need confirmation in studies that take into account the potential confounding factors and the known risk factors for these individual sites. The evidence 104 for parental smoking and childhood cancer is also not clear, and evaluation of this association is made difficult by the various definitions of exposure that have been used, including maternal and paternal smoking before, during, and after the pregnancy. Mothers and fathers who smoke during a pregnancy generally smoked before the conception and continue to smoke after the pregnancy. Thus, an effect of involuntary smoking after birth cannot readily be distin- guished from genetic or transplacentally mediated effects. Cardiovascular Diseases A causal association between active cigarette smoking and cardio- vascular disease is well established (US DHHS 1983). The relation- ship between cardiovascular disease and involuntary smoking has been examined in one case-control study and three prospective studies. In the case-control study by Lee and colleagues (1986), described previously, ischemic heart disease cases and controls did not show a statistically significant difference in their exposure to involuntary smoking, based on the smoking habits of spouses or on an index accounting for exposure at home, at work, and during travel and leisure. In the Japanese cohort study, Hirayama (1984b, 1985) reported an elevated risk for ischemic heart disease (N=494) . in nonsmoking women married to smokers. The standardized mortality ratios when the husbands were nonsmokers, ex-smokers or smokers of 19 or more cigarettes per day, and smokers of 20 or more cigarettes per day were 1.0, 1.10, and 1.31, respectively (one-sided p for trend, 0.019). In the Scottish followup study (Gillis et al. 1984), nonsmokers not exposed to tobacco smoke were compared with nonsmokers exposed to tobacco smoke with respect to the prevalence of cardiovascular symptoms at entry and mortality due to coronary heart disease. There was no consistent pattern of differences in coronary heart disease or symptoms between nonsmoking men exposed to tobacco smoke and their nonexposed counterparts. Nonsmoking women exposed to tobacco smoke exhibited a higher prevalence of angina and major ECG abnormality at entry, and also a higher mortality rate for all coronary diseases. However, rates of myocardial infarc- tion mortality were higher for exposed nonsmoking men and women compared with the nonexposed nonsmokers. The rates were 31 and 4 per 10,000, respectively, for the nonexposed nonsmoking men and women, and 45 and 12 per 10,000, respectively, for the exposed nonsmoking men and women. None of the differences were tested for statistical significance. In the Japanese and the Scottish studies, other known risk factors for cardiovascular diseases, i.e., systolic blood pressure, plasma cholesterol, were not accounted for in the analysis. 105 In a study of heart disease, Garland and coworkers (1985) enrolled 82 percent of adults aged 50 to 79 between 1972 and 1974 in a predominantly white, upper-middle-class community in San Diego, California. Blood pressure and plasma cholesterol were measured at entry, and all participants responded to a standard interview that asked about smoking habits, history of heart disease, and other health-related variables. Excluding women who had a previous history of heart disease or stroke or who had ever smoked, 695 | currently married nonsmoking women were classified by their husbands’ self-reported smoking status at enrollment. After 10 years of followup, there were 19 deaths due to ischemic heart disease; the age-standardized mortality rates.for nonsmoking wives whose hus- bands were nonsmokers, ex-smokers, and current smokers were 1.2, 3.6, and 2.7, respectively (one-sided p for trend, <0.10). After adjustment for age, systolic blood pressure, total plasma cholesterol, obesity index, and years of marriage, the relative risk for death due to ischemic heart disease for women married to current or former smokers at entry compared with women married to never smokers was 2.7 (one-sided p <0.10). The study’s findings are not convincing from the point of view of sample stability. The total number of deaths due to ischemic heart disease was small, and the denominator in the relative risk calculation is unstable, based on the deaths of two women whose husbands had never smoked. Moreover, it is well established that the risk of coronary heart disease is substantially lower among those who have stopped smoking (US DHHS 1988), although the amount of time required for this change after cessation of smoking is not clear (Kannel 1981). In this study, 15 of 19 deaths occurred in nonsmoking women married to husbands who had stopped smoking at entry, and the age-standardized rate for ischemic heart disease was highest in this group. The high proportion of deaths in nonsmoking women married to men who became ex-smokers implies that the excess resulted from a sustained effect of involuntary smoking. More detailed characterizations of exposure to ETS and specific types of cardiovascular disease associated with this exposure are needed before an effect of involuntary smoking on the etiology of cardiovas- cular disease can be established. One study (Aronow 1978a,b) suggested that involuntary smoking aggravates angina pectoris. This study was criticized because the end point, angina, was based on subjective evaluation, and because other factors such as stress were not controlled for (Coodley 1978; Robinson 1978; Waite 1978; Wakehan 1978). More important, the validity of Aronow’s work has been questioned (Budiansky 1983). 106 Conclusions 1. Involuntary smoking can cause lung cancer in nonsmokers. 2. Although a substantial number of the lung cancers that occur in nonsmokers can be attributed to involuntary smoking, more data on the dose and distribution of ETS exposure in the population are needed in order to accurately estimate the magnitude of risk in the U.S. population. 3. The children of parents who smoke have an increased frequen- cy of hospitalization for bronchitis and pneumonia during the first year of life when compared with the children of nonsmok- ers. 4. The children of parents who smoke have an increased frequen- cy of a variety of acute respiratory illnesses and infections, including chest illnesses before 2 years of age and physician- diagnosed bronchitis, tracheitis, and laryngitis, when com- pared with the children of nonsmokers. 5.Chronic cough and phlegm are more frequent in children whose parents smoke compared with children of nonsmokers. The implications of chronic respiratory symptoms for respirad tory health as an adult are unknown and deserve further study. 6. The children of parents who smoke have small differences in tests of pulmonary function when compared with the children of nonsmokers. Although this decrement is insufficient to cause symptoms, the possibility that it may increase suscepti- bility to chronic obstructive pulmonary disease with exposure to other agents in adult life, e.g., active smoking or occupation- al exposures, needs investigation. 7. Healthy adults exposed to environmental tobacco smoke may have small changes on pulmonary function testing, but are unlikely to experience clinically significant deficits in pulmo- nary function as a result of exposure to environmental tobacco smoke alone. 8. A number of studies report that chronic middle ear effusions are more common in young children whose parents smoke than in children of nonsmoking parents. 9. Validated questionnaires are needed for the assessment of recent and remote exposure to environmental tobacco smoke in the home, workplace, and other environments. 10. The associations between cancers, other than cancer of the lung, and involuntary smoking require further investigation before a determination can be made about the relationship of involuntary smoking to these cancers. 11. 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British Journal of Diseases of the Chest 73(3):230-236, July 1979. 119 CHAPTER 3 ENVIRONMENTAL TOBACCO SMOKE CHEMISTRY AND EXPOSURE OF NONSMOKERS CONTENTS Introduction Laboratory Smoking Human Smoking Sidestream Smoke Formation and Physicochemical Nature Chemical Analysis Radioactivity of Tobacco Smoke Environmental Tobacco Smoke Comparison of Toxic and Carcinogenic Agents in Main- stream Smoke and in Environmental Tobacco Smoke Number and Size Distribution of Particles in Environ- mental Tobacco Smoke Estimating Human Exposure to Environmental Tobacco Smoke Time-Activity Patterns Temporal and Spatial Distribution of Smokers Determinations of Concentration of Environmental Tobacco Smoke Microenvironmental Measurements of Concentration Monitoring Studies Conclusions References 123 Introduction The physicochemical nature of environmental tobacco smoke (ETS) is governed by the type and form of the tobacco product or products burned, by the prevailing environmental conditions, and by secondary reactions. Mainstream smoke (MS) is the complex mixture that exits from the mouthpiece of a burning cigarette, cigar, or pipe when a puff is inhaled by the smoker. Sidestream smoke (SS) is formed between puff-drawings and is freely emitted into the air surrounding a smoldering tobacco product. Sidestream smoke repre- sents the major source for ETS. The exhaled portions of MS and the vapor phase components that diffuse through the wrapper into the surrounding air constitute minor contributors to ETS. In the scientific literature, the terms “passive smoking,” “involun- tary smoking,” and “inhalation of ETS” are frequently used inter- changeably (US DHEW 1979; US DHHS 1982, 1984). Laboratory Smoking Data on the composition of MS and SS originate from laboratory studies. For such studies, cigarettes, cigars, or pipes are smoked by machines under standardized reproducible conditions. It is a major goal of these measurements to compare the yields of the specific components in the MS or SS or both of a variety of experimental or commercial tobacco products and to simulate, though not to repro- duce, human smoking habits. The most widely used standard conditions for machine smoking cigarettes and little cigars (< 1.5 g) are one 35 mL puff of 2-second duration drawn once a minute to a butt length of 23 mm, or the length of the filter tip plus the overwrap plus 3 mm (Brunnemann et al. 1976). The annual reports of the U.S. Federal Trade Commission on the tar, nicotine, and carbon monox- ide content of the smoke of U.S. commercial cigarettes are based on these laboratory smoking conditions. For cigars, the standard smoking conditions are a 20 mL puff of 1.5-second duration taken once every 40 seconds, and a butt length of 33 mm (International Committee for Cigar Smoke Study 1974). The most frequently used pipesmoking conditions call for the bowl to be filled with 1 g of tobacco and a 50 mL puff of 1-second duration to be taken every 12 seconds (Miller 1964). A number of devices for collecting sidestream smoke have been developed (Dube and Green 1982). The most widely used device is a collection apparatus made of glass and cooled by water circulating through an outer jacket. The air entering the chamber through a distributor has a flow rate of 25 mL per second (4.5 L/min) (Brunnemann and Hoffmann 1974). Under these conditions, the yields of mainstream smoke components from a cigarette approxi- mate those obtained from the same cigarette when it is being smoked 125 in the open air. However, the velocity of the airstream through the chamber has considerable influence on the yields of individual compounds in SS (Klus and Kuhn 1982). . To collect the particulate phase of MS and SS, the smoke aerosols are passed through a glass fiber filter (a Cambridge filter with a diameter of 45 mm) that traps more than 99 percent of all particles with a diameter of at least 0.1 jm (Wartman et al. 1959). The portion of the smoke that passes through the glass fiber filter is arbitrarily designated as vapor phase, although it is realized that this separa- tion does not fully reflect the actual physicochemical conditions prevailing in MS and SS. For the analysis of individual components or a group of components, specific trapping devices and methods have been developed (Dube and Green 1982). Human Smoking The standardized machine-smoking conditions used in the tobacco laboratory were set up to simulate the parameters of human smoking as practiced 30 years ago. The examination of current smoking practices suggests that machine-smoking conditions no longer reflect current practices. Human smoking patterns depend on a number of factors, one of which is the delivery of nicotizie. Dosimetry of smoke constituents has shown that low nicotine delivery (<0.6 to 1.0 mg/cigarette) generally induces the smoker to draw larger puff volumes (up to 55 mL per puff), to puff more frequently (three to five times a minute), and to inhale more deeply (Herning et al. 1981). Furthermore, many smokers of cigarettes with perforated filter tips tend to obstruct the holes in these tips by pressing their lips around them; thus, they inhale more smoke than would be expected according to the machine-smoking data (Kozlow- ski et al. 1980). Smokers of cigarettes with a longitudinal air channel in the filter tip compress the tip in a similar manner so that the mainstream smoke delivery is increased over that measured with the laboratory methodology (Hoffmann et al. 1983). These deviations from machine-smoking patterns cause a greater amount of tobacco to be consumed during MS generation. Conse- quently, the quantity of tobacco burned between puffs is diminished, and lower amounts of combustion products are released as SS. Because of the proximity to the burning tobacco product, the active smoker usually inhales more of the SS and ETS than a nonsmoker. It is not known to what extent the different constituents of inhaled ETS aerosols can be retained in the respiratory tract of nonsmokers. Studies with MS have shown that more than 90 percent of the volatile, hydrophilic components are retained by the smoker (Dal- hamn et al. 1968a) and that less than 50 percent of the volatile, hydrophobic MS components are retained by the smoker (Dalhamn et al. 1968b). On the basis of these data, it may be assumed that the 126 passive smoker retains a high percentage of the vapor phase components of ETS and significantly less of its hydrophobic volatiles. Sidestream Smoke Formation and Physicochemical Nature When nonfilter cigarettes are being smoked under standardized conditions, approximately 45 percent of the tobacco column is consumed during the generation of MS (puff-drawing), whereas the remainder is burned between puffs and under conditions of a strongly reducing atmosphere. In addition, MS and SS is generated at distinctly higher temperatures than SS (Wynder and Hoffmann 1967). Thus, undiluted SS contains more tobacco-derived combustion products than does MS, and contains especially greater quantities of those combustion products that are formed by nitrosation or amination. Consequently, the composition of SS differs from that of MS. The SS of a smoldering cigarette enters the surrounding atmo- sphere about 3 mm in front of the paper burn line, at about 350° C (Baker 1984). In Table 1, the MS and the SS from nonfilter cigarettes are compared. Under standardized conditions, the formation of the MS of a nonfilter cigarette (80 mm, 1,230 mg) is completed during 10 puffs, requires 20 seconds, and consumes 347 mg of tobacco. The formation of SS from the same cigarette during smoldering requires 550 seconds and consumes 411 mg of tobacco (Neurath and Horst- mann 1963). The pH of the MS of a blended U.S. cigarette ranges from 6.0 to 6.2 and the pH of SS, from 6.7 to 7.5. Above pH 6, the proportion of unprotonated nicotine in undiluted smoke rises; at pH 7.9, about 50 percent is unprotonated. Therefore, SS contains more free nicotine in the vapor phase than MS. The reported measurements of the pH of cigars were 6.5 to 8.5 for MS and 7.5 to 8.7 for SS; measurements for the pH of SS from pipes have not been published (Brunnemann and Hoffmann 1974). Chemical Analysis In order to establish reproducible chemical-analytical data, ciga- rette SS is generated in a special chamber. This assures that the cigarettes burn evenly during puff intervals when an airstream at a velocity of 25 mL per second is drawn through the chamber. At this flow rate in the chamber, MS generation is quantitatively similar to that measured without the SS chamber (Neurath and Ehmke 1964; Brunnemann and Hoffmann 1974; Dube and Green 1982). Through- out this chapter the data refer primarily to MS, SS, and ETS deriving from cigarettes and not from cigars or pipes, because 127 TABLE 1.—Comparison of mainstream smoke (MS) and sidestream smoke (SS) of a nonfilter cigarette: Some physicochemical data Study Parameters MS ss Neurath and Horstmann Duration of smoke production (sec) 20 550 “1963) Tobacco burned (mg) 347 411 ynder and Hoffmann Peak temperature during formation (°C) 900 =x600 967) Brunnemann and pH of total aerosol 6.0-6.2 6.7-7.5 Hoffmann (1974) Scassellati-Sforzolini Number of particles per cigarette? 10.5 x 10% 3.5 x 10" and Savino (1968) , Carter and Hasegawa Particle sizes (nm)? 0.1-L.0 0.01-0.8 (1975); Hiller et al. Particle mean diameter (nm)* 0.4 0.32 (1982) Wynder and Hoffmann Smoke dilution (vol %)? (1967); Keith and "OO Derrick (1960); Carbon monoxide 3-5 2-3 Baker (1984); Hoffmann, Brunnemann Carbon dioxide 811 46 et al. (1984) Oxygen 12-16 15-2 Hydrogen 3-15 0.8-1.0 NOTE: Data obtained under standard laboratory smoking conditions of 1 puff per minute of 2-second duration and 35 mL volume. . * Fresh and undiluted mainstream smoke and sidestream smoke. *Four mm distant from the burning cone (gas temperature, 350° C). cigarette smoke is the major source of ETS in public places. Few data are available on the SS and ETS from cigars and pipes. About 300 to 400 of the several thousand individual compounds identified in tobacco smoke have been quantitatively determined in both mainstream and 'sidestream smoke. A listing of selected agents in the MS of nonfilter cigarettes with their reported range of concentration and their relative ratio of distribution in SS compared with MS is presented in Table 2. Values greater than 1.0 reflect the greater release of a given compound into SS than into MS. The grouping of the compounds in Table 2 into vapor phase components and particulate phase constituents refers to the makeup of MS, but does not represent the physicochemical distribution of these com- pounds in SS. Some of the volatile compounds in MS and SS are compared. On the basis of the amount of tobacco burned in the MS and SS of a nonfilter cigarette (see Table 1), the ratio of SS to MS should be 1.2 to 1.5 if the combustion conditions during both phases of smoke generation were comparable. However, this is not the case, 128 as is indicated by the higher SS to MS ratios for carbon monoxide (2.5-4.7), carbon dioxide (8-11), acrolein (8-15), benzene (10), and other smoke constituents. The high yield of carbon monoxide and carbon dioxide in SS indicates that more carbon monoxide is generated during smoldering than during puff-drawing. After passing very briefly through the hot cone, most of the carbon monoxide gas in both MS and SS is oxidized to carbon dioxide, most likely owing to the high temperature gradient and the sudden exposure to environmental oxygen upon emission.. The higher yields of volatile pyridines in SS compared with MS are probably caused by the preferred formation of these compounds from the alkaloids during smoldering (Schmeltz et al. 1979). In contrast, hydrogen cyanide (HCN) is primarily formed from protein at temperatures above 700° C (Johnson and Kang 1971), and the smoldering of tobacco at about 600° C does aot yield the pyrosynthe- sis of HCN to the extent that it occurs at the higher temperatures present during MS generation. The very high levels of ammonia, nitrogen oxide, and the volatile N-nitrosamines in SS compared with the levels in MS is striking. Studies with “N-nitrate have under- scored that the burning of tobacco results in the reduction of nitrate to ammonia, and that the latter is released to a greater extent during SS formation than during puff-drawing (Johnson et al. 1973). In a blended cigarette, this higher level of ammonia in SS causes its elevated pH to reach levels of 6.7 to 7.5, while the pH of MS is about 6 (Brunnemann and Hoffmann 1974). The increased release of the highly carcinogenic volatile N-nitrosa- mines into SS (20 to 100 times greater than into MS) has been well established (Brunnemann et al. 1977). The carcinogenic potential of SS may also be affected by the levels of the oxides of nitrogen (NO). Four to ten times more nitrogen oxide (NO) is released into the environment in sidestream smoke than is inhaled with the main- stream smoke. The smoker inhales more than 95 percent of the NOx in the form of NO, and only a small portion is oxidized to the powerful nitrosating agent nitrogen dioxide (NO,). Only a fraction of NO is expected to be retained in the respiratory system of smokers by being bound to hemoglobin. The NO, gases released into the environment are partially oxidized to NO, (Vilcins and Lephardt 1975). Therefore, sidestream smoke-polluted environments are ex- pected to contain the hydrophilic nitrosating agent NO2. Data for particulate matter and some of its constituents in MS and SS are also listed in Table 2. The release of tobacco-specific N- nitrosamines into SS is up to four times higher than that into MS. Whether the distribution of these agents in the vapor phase and the particulate phase of SS is of major consequence with respect to the carcinogenic potential of SS needs to be determined. It is equally 129 O&T TABLE 2.—Distribution of constituents in mainstream smoke (MS) and the ratio of sidestream smoke (SS) to MS of nonfilter cigarettes Vapor phase constituents! range eat Particulate phase constituents! range eco. Carbon monoxide 10-23 mg 2.5-4.7 Particulate matter? 15-40 mg 13-19 Carbon dioxide 20-40 mg $11 Nicotine - 1-2.5 mg 26-33 Carbonyl! sulfide 18-42 pg 0.03-0.13 Anatabine 2-20 pg <0.1-0.5 Benzene? 12-48 pg 10 Phenol 60-140 pg 16-30 — Toluene 160 pg 6 Catechol 100-360 pg 0.6-0.9 Formaldehyde 70-100 pg 0.1250 Hydroquinone 110-300 pg 0.7-0.9 Acrolein 60-100 pg 8-15 Aniline 360 ng 30 Acetone 100-250 pg 2-5 2-Toluidine 160 ng 19 Pyridine 16-40 pg 6.5-20 2-Naphthylamine? 17 ng . 30 3-Methylpyridine 12-36 pg 3-13 4-Aminobipheny]* 4.6 ng 31 3-Vinylpyridine 11-30 pg 20-40 Benz{ajanthracene* 20-70 ng 24 Hydrogen cyanide 400-500 pg 0,1-0.25 Benzofa]pyrene*® 20-40 ng 2.5-3.5 Hydrazine® 32 ng 3 Cholesterol 22 pg 0.9 Ammonia 50-130 pg 40-170 ; y-Butyrolactone‘ 10-22 pg 3.6-5.0 Methylamine 11.5-28.7 pg 4.2-6.4 Quinoline » 0.5-2 pg 811 Dimethylamine 78-10 pg 3.7-5.1 Harman 17-3.1 pg O.7-1.7 Nitrogen oxide 100-600 pg 410 N'-Nitroeonornicotine‘ 200-3,000 ng 0.5-3 TABLE 2.—Continued MS “SS/MS MS SS/MS Vapor phase constituents' range ratio Particulate phase constituents? range ratio N-Nitrosodimethylamine* 10-40 ng 20-100 NNK* 100-1,000 ng 4 N-Nitrosopyrrolidine* 6-30 ng 6-30 N-Nitrosodienthanolamine* 20-70 ng 12 Formic acid 210-490 pg 14-16 Cadmium 100 ng 12 Acetic acid 330-810 pg 1.9-3.6 Nickel? 20-80 ng 13-30 Zinc 60 ng 6.7 Polonium-210? 0.04-0,1 pCi 1.0-4.0 Benzoic acid 14-28 pg 0.67-0,95 Lactic acid 63-174 pg 0.5-0.7 Glycolic acid 37-126 pg 0.6-0.95 Succinic acid 110-140 pg 0.43-0.62 ’ Values are given for fresh and undiluted MS and SS. 2 Human carcinogen (IARC 1986). ® Suspected human carcinogen (IARC 1986). * Animal carcinogen (IARC 1986). SOURCE: Elliott and Rowe (1975); Hoffmann et al. (1983); Klus and Kuhn (1982); Sakuma et al. (1983); Sakuma, Kusama, Yamaguchi, Matsuki et al. (1984); Sakuma, Kusama, Yamaguchi, Sugawara (1984); Schmeltz et al. (1975). important to examine the significance of the abundant release of amines into SS (levels are up to 30 times higher than in MS), indicated by the data for aniline, 2-toluidine, and the alkaloids. This is of concern because certain amines are readily nitrosated to N- nitrosamines. However, analytical data on secondary reactions of amines in polluted environments are lacking. For a meaningful interpretation of the data on the distribution of the compounds in cigarette smoke presented in Table 2, certain aspects of the methodology should be emphasized. First, the data are based on analyses of nonfilter cigarettes that were smoked under standardized laboratory conditions. Second, the standardized ma- chine-smoking conditions were established according to human smoking patterns observed three decades ago and do not reflect the smoking behavior of contemporary smokers. This caveat applies particularly to smoking patterns observed with filter cigarettes designed for low smoke yields. Most consumers of these cigarettes inhale the smoke more intensely than smokers of nonfilter cigarettes (Herning et al. 1981; Hill et al. 1983). This change in smoking intensity affects the delivery of the sidestream smoke. The conven- tional filter tips of cigarettes influence primarily the yield of MS and have little impact on SS yield. However, in the case of cigarettes with specially designed filter tips such as perforations, the yield of SS is also affected (Table 3) (Adams et al. 1985). Radioactivity of Tobacco Smoke Naturally occurring decay products of radon are found in tobacco and, therefore, also in tobacco smoke. These include the isotopes of lead (Pb-210), bismuth (Bi-210), polonium (Po-210), and radon, which originates from the decay of uranium through radium (Radford and Hunt 1964; Martell 1975). Radon and its short-lived daughters (Po- 218, Pb-214, Bi-214, Po-214), which precede long-lived daughters in the decay chain, are ubiquitous in indoor air and are largely derived from sources other than tobacco smoke. Most of the radon daughters are attached to particles in the air, but a small proportion, referred to as the unattached fraction, is not (Raabe 1969; Kruger and Nothling 1979; Bergman and Axelson 1983). It has been suggested that the presence of Pb-210 and subsequent decay products in tobacco is dependent upon an absorption of short- lived radon daughters on the leaves of the tobacco plant, especially where phosphate fertilizers that are rich in radium have been used and have caused increased leakage of radon from the ground. These attached short-lived radon daughters then decay to long-lived Pb-210 and subsequent nuclides found in the tobacco (Fleischer and Parungo 1974; Martell 1975). However, the origin of these decay products may 132 e&T TABLE 3.—Distribution of selected components in the sidestream smoke (SS) and the ratio of SS to mainstream smoke (MS) of four U.S. commercial cigarettes Cigarette A Cigarette B Cigarette C Cigarette D 85 mm NF 85 mm F 85 mm F 85 mm PF Components ss SS/MS Ss SS/MS SS SS/MS SS SS/MS Tar (mg/g) 22.6 11 24.4 16 20.0 29 14.1 15.6 Nicotine (mg/g) 4.6 2.2 40 2.7 3.4 4.2 3.0 20.0 Carbon monoxide (mg/g) 28.3 2.1 36.6 2.7 33.2 3.5 26.8 14.9 Ammonia (mg/g! 524 7.0 893 46 213.1 6.3 236 5.8 Catechol qug/z) 58.2 14 89.8 13 69.5 2.6 117 129 Benzolalpyrene (ng/g) 67 2.6 45.7 2.6 51.7 4.2 448 20.4 N-Nitrosodimethyamine (ng/g) 735 23.6 597 139 611 50.4 685 167 N-Nitrosopyrrolidine (ng/g) 177 2.7 139 13.6 233 TA 234 17.7 N’-Nitrosonornicotine (ng/g) 857 0.85 307 0.63 185 0.68 338 5.1 NOTE: NF, nonfilter cigarette: F, filter cigarette: PF, cigarette with perforated filter tip: values given are for fresh and undiluted sidestream and mainstream smoke. SOURCE: Adams et al. (1985) also depend on the general occurrence of radon in the atmosphere and not on the local emanation of radon (Hill 1982). In recent years, it has been shown that relatively high levels of radon and short-lived radon daughters may occur in indoor air, and consistent observations in this regard have been made in several countries (Nero et al. 1985). In the air with a very low concentration of particles, the proportion of unattached radon daughters is increased beyond that found with a higher concentration of particles. The unattached daughters are removed more rapidly than those that are attached by plating out on walls and fixtures. The addition of an aerosol, such as tobacco smoke, increases the attached fraction, elevates the concentration of radon daughters, and reduces the rate of removal of radon daughters (Bergman and Axelson 1983). The dose of a radiation received by the airway epithelium depends not only on the concentration of radon daughters but also on the unattached fraction and on the size distribution of the inhaled particles. The interplay among these factors as they are modified by ETS has not yet been fully examined. Environmental Tobacco Smoke The air dilution of sidestream smoke, and of other contributors to ETS, causes several physicochemical changes in the aerosol. The concentration of particles in ETS depends on the degree of air dilution and may range from 300 to 500 mg/m‘ to a few g/m’. At the same time, the median diameter of particles may decrease as undiluted SS is diluted to form ETS (Keith and Derrick 1960; Wynder and Hoffmann 1967; Ingebrethsen and Sears 1986). Further- more, nicotine volatilizes during air dilution of SS, so that in ETS it occurs almost exclusively in the vapor phase (Eudy et al. 1985). This is reflected in the fairly rapid occurrence of relatively high concen- trations of nicotine in the saliva of people entering a smoke-polluted room (Hoffmann, Haley et al. 1984). Most likely there are also redistributions between the vapor phase and the particulate phase of other constituents in SS due to air dilution, which may account for the presence of other semivolatiles in the vapor phase of ETS. However, evidence of such effects needs to be established. Comparison of Toxic and Carcinogenic Agents in Mainstream Smoke and in Environmental Tobacco Smoke The combustion products of cigarettes are the source of both environmental tobacco smoke and mainstream smoke. Therefore, comparisons of the levels of specific toxins and carcinogens in ETS with the corresponding levels in the mainstream smoke are relevant to an estimation of the risk of ETS exposure. Although ETS is a far 134 less concentrated aerosol than undiluted MS, both inhalants contain the same volatile and nonvolatile toxic agents and carcinogens. This fact and the current knowledge about the quantitative relationships between dose and effect that are commonly observed from exposure to carcinogens have led to the conclusion that the inhalation of ETS gives rise to some risk of cancer (IARC 1986). However, comparisons of MS and ETS should include the consider- ation of the differences between the two aerosols with regard to their chemical composition, including pH levels, and their physicochemi- cal nature (particle size, air dilution factors, and distribution of agents between vapor phase and particulate phase). Another impor- tant consideration pertains to the differences between inhaling ambient air and inhaling a concentrated smoke aerosol during puff- drawing. Finally, chemical and physicochemical data established by the analysis of smoke generated by machine-smoking are certainly not fully comparable to the levels and characteristics of compounds generated when a smoker inhales cigarette smoke. This caveat applies particularly to the smoking of low-yield cigarettes, for which the yields of smoke constituents in machine-generated smoking and human smoking activities may be most divergent (Herning et al. 1981). The levels of certain smoke constituents in the mainstream smoke of one cigarette compared with the amounts of such compounds inhaled as constituents of ETS in 1 hour at a respiratory rate of 10 L per minute are presented in Table 4. Unaged MS does not contain nitrogen dioxide (NO.<5 yg/cigarette) because the nitrogen oxides generated during tobacco combustion in the reducing atmosphere of the burning cone are transported in the smoke stream (=10 vol % O,) to the exit of the cigarette mouthpiece in less than 0.2 seconds, and it takes 500 seconds for half of the nitrogen oxide in MS to oxidize to nitrogen dioxide (Neurath 1972). The relatively low values for nicotine reported in ETS may be explained, in part, by the inefficiency of the trapping devices for collecting all of the available nicotine; the alkaloid is predominantly in the vapor phase, which escapes retention by the filters of such devices. The assignment of benzene as a “human carcinogen,” benzo- {alpyrene as a “suspected human carcinogen,” and N-nitrosodi- methylamine and N-nitrosodiethylamine as “animal carcinogens” is based on definitions by the International Agency for Research on Cancer (1986). Accordingly, a human carcinogen is an agent for which “sufficient evidence of carcinogenicity indicates that there is a causal relationship between exposure and human cancer.” A sus- pected human carcinogen is an agent for which “limited evidence of carcinogenicity indicates that a causal interpretation is credible, but that alternate explanations, such as chance, bias, or confounding, could not adequately be excluded.” An animal carcinogen is an agent 135 9ET TABLE 4.—Concentrations of toxic and carcinogenic agents in nonfilter cigarette mainstream smoke and in environmental tobacco smoke (ETS) in indoor environments : Inhaled as ETS constituents during 1 hour Mainstream Smoke Range Episodic high values’ Agent Weight Concentration Weight Concentration Weight Concentration Carbon monoxide 10-23 mg 24,9000-57,300 ppm 1.2-22 mg 1-18.5 ppm 37 mg 32 ppm Nitrogen oxide 100-600 pg 230,000~1,400,000 ppb 7-90 ug 9-120 ppb 146 pg 195 ppb Nitrogen dioxide <5 ug <7,600 ppb 24-87 pg ‘21-76 ppb 120 pg 105 ppb Acrolein 60-100 pg 75,000-125,000 ppb &72 ug 6-50 ppb 110 pg 80 ppb Acetone 100-250 pg 120,000-300,000 ppb 210-720 pe 150-500 ppb 3,500 pg 2,400 ppb Benzene? 12-48 pg 11,000-43,000 ppb 12-190 pg 6-98 ppb 190 pg 98 ppb N-Nitrosodimethylamine* 10-40 ng 9-38 ppb 6-140 ng 0.003-0.072 ppb 140 ng 0.072 ppb N-Nitrosodiethylamine® 4-25 ng 3-17 ppb <6-120 ng <0,002-0.05 ppb 120 ng 0.05 ppb Nicotine 1,000-2,500 pg 430,000-1,080,000 ppb 0.6-30 pg 0.15-7.5 ppb 300 pg 75 ppb Benzofa}pyrene * 20-40 ng 5-11 ppb 17-460 ng 0.0002-0.04 ppb 460 ng 0.04 ppb NOTE: Values for inhaled mainatream amoke P ts were calculated from values in Table 2 and on a respiratory rate of 10 L per minute. Values for carbon monoxide and nicotine represent the range in mainstream smoke of U.S. nonfilter cigarettes as reported by the U.S. Federal Trade Commission (1985). Data under ETS are derived from Tables 8 through 15, with data from the unventilated interior compartments of automobiles excluded (Badre et. al. 1978). The designation “episodic high values” was chosen to classify those data in the literature that require confirmation, * Human carcinogen according to the IARC (Vainio et al. 1985) and suspected carcinogen according to the ACGIH (1985). * Animal carcinogen according to the IARC (Vainio et al. 1985). *Suspected human carcinogen, according to the IARC (Vainio et al. 1985) and according to the ACGIH (1986). “for which there is sufficient evidence of carcinogenicity in animals but for which no data on humans are available.” Polonium-210 is not listed in Table 4 because there are no data on the concentration of this isotope in ETS, although it is a component of both MS and SS. Whereas in clean air the short-lived radon daughters tend to plate out on room surfaces, in the presence of an aerosol such as ETS, some of the short-lived radon daughters become attached to particles and consequently remain available for inhala- tion. Radon daughter background concentration may more than double in the presence of ETS (Bergman and Axelson 1983). Number and Size Distribution of Particles in Environmental Tobacco Smoke Environmental tobacco smoke consists of the combined products of both fresh and aged sidestream smoke and exhaled mainstream smoke. Coagulation, evaporation, and particle removal on surfaces occur simultaneously to modify the physical characteristics of the ETS particles; as a result, the “typical” particle size and chemical composition of ETS may vary with the age of the smoke and the characteristics of the environment. Other factors such as relative humidity, particle concentration, and temperature may also affect the characteristics of ETS. The rapid dilution of SS smoke as it is emitted into a room leads to a number of physical and chemical changes. For example, the evaporation of volatile species as the ETS ages reduces the median diameter of the smoke particles. Several studies have measured the particle distribution of SS under controlled conditions (Table 5), and indicate that the mass median diameter (MMD) of ETS is between approximately 0.2 jm and 0.4 um. The differences among the studies reflect the varying analytical methods. ETS particles are in the diffusion-controlled regime for particle removal and therefore will tend to follow stream lines, remain airborne for long periods of time, and rapidly disperse through open volumes. As indicated, a number of factors can produce variation in the mean size of the particles in ETS; however, in considering transport, deposition, and removal in the human lung, it is useful to assume that the particle sizes of aged ETS will generally be between 0.1 and 0.4 um. Although the results presented in Table 5 do not permit the assignment of a single value for the diameter of sidestream smoke particles, the difference in deposition efficiency in the human respiratory tract of 0.2 um particles and 0.4 un particles is negligible (Chan and Lippmann 1980). Particles in this size range are not efficiently removed by sedimentation or impaction. Although diffu- sion is the major removal mechanism for particles of this size, it is minimally efficient in the 0.2 to 0.4 tm range. The relatively low 137 8éT TABLE 5.—Summary of sidestream smoke size distribution studies Count Mass Geometric Chamber median median standard Number Study Cigarette Method concentration (yg/m*) diameter diameter deviation per cm’ Keith and Derrick Blended “Conifuge” Not reported 0.15 Not reported Not reported 3.8 x 10" (1960) Porstendérfer and Not reported CNC/diffusion tube Not reported 0.24 Not reported Not reported 3.3 x 107 Schraub (1972) Hiller et ai. Not reported SPART analyzer 50-100 0.32 0.41 15 Not reported (1982) Leaderer et al. Commercial EAA 700 Not reported 0.225 21 Not reported (1984) Ingebrethsen and MC/CNC 0.2 16 Sears (1986) NOTE: CNC ~ Condensation nucleus counter; SPART = Single particle aerodynamic relaxation time analyzer; EAA -: Electrical aerosol analyzer; MC = Mobility classifier particle deposition efficiency for SS particles in human volunteers observed by Hiller and colleagues (1982) is consistent with particles in this size range. Several investigators have measured the size distribution of MS smoke (Table 6). As is the case with SS smoke, the different instruments and methodologies employed yielded differing results. For purposes of comparison, only two sets of studies utilizing similar instruments are discussed. McCusker and colleagues (1983), using a single particle aerodynamic relaxation time (SPART) analyz- er to study highly diluted MS smoke particles, found a mass median diameter of 0.42 »m with a geometric standard deviation (GSD) of 1.38. Hiller and colleagues (1982) used the SPART analyzer on SS smoke particles and found a mass median diameter of 0.41 ym and GSD of 1.5. Chang and colleagues (1985) used an electrical aerosol analyzer (EAA) to measure MS for various dilution ratios and reported a MMD of 0.27 pm (GSD 1.26) for the highest dilution. Leaderer and colleagues (1984) used an EAA to determine the size distribution for SS smoke particles in an environmental chamber and determined an MMD of 0.23 um (GSD 2.08). These results also show that studies utilizing similar instruments provide similar results for the size distribution of both SS and MS particles. As discussed in an earlier section, however, the chemical composition of the MS and ETS particles can be quite different because of the very different conditions of their generation and the subsequent dilution and aging ETS undergoes before inhalation. Estimating Human Exposure to Environmental Tobacco Smoke Human exposure to ETS can be estimated using approaches similar to those used for other airborne pollutants. The concentra- tion of ETS to which an individual is exposed depends on factors such as the type and number of cigarettes burned, the volume of the room, the ventilation rate, and the proximity to the source. These factors, along with the duration of exposure and individual characteristics such as ventilatory rate and breathing pattern, dictate the dosage received by an individual. Ideally, the health effects of exposures to ETS might be assessed by quantifying the time-dependent exposure dose for each of the several thousand compounds in cigarette smoke and defining the dose— response relationships for these compounds in producing disease, both as isolated compounds and in various combinations. The magnitude of this task, given the number of compounds in smoke, and the limited knowledge of the precise mechanisms by which these compounds cause disease have led to a simpler approach, one that attempts to use measures of exposure to individual smoke constitu- ents as estimates of whole smoke exposure. The accuracy with which 139 OFT TABLE 6.—Summary of mainstream smoke size distribution studies Count Mass median median Geometric Dilution diameter diameter standard Concentration Study Cigarette Method ratio (um) (um) deviation (number/cm!) Keith and Derrick Blended “Conifuge” 295 0.23 Not reported 16 5.3 x 10° (1960) . Porstendirfer and Not reported CNC/diffusion tube Not reported 0.22 Not reported Not reported Not reported Schraub (1972) Okada and Blended Light scattering 1500 0.18 0.29 15 3 x 10° Matsunama (1974) Hinds (1978) Commercial Cascade impactor 10 Not reported 0.52 1.35 Not reported Cascade impactor 50 Not reported 0.44 144 Not reported Cascade impactor 100 Not reported 0.39 1.43 Not reported Aerosol certifuge 100 Not reported 0.38 1.33 Not reported Aerosol certifuge 320 Not reported 0.38 137 Not reported Aerosol certifuge 500 Not reported 0.38 1,35 Not reported Aerosol certifuge 700 Not reported 0.37 131 Not reported McCusker et al. 2R1 SPART analyzer 1.26 x 10° 0.36 0.42 1.38 42 x 10° (1983) Chang et al. 2R1 EAA 6 0.25 0.30 1.27 42x 10° (1985) 10 0.24 0.26 1.18 3.6 x 10° 18 0,22 0.26 1.26 7x10 NOTE: CNC = Condensation nucleus counter; SPART = Single particle aerodynamic relaxation time analyzer; EAA = Electrical aeroeol analyzer, measurements of a single compound reflect exposure to whole smoke is limited by the changes in the composition of ETS with time and the conditions of exposure. For this reason, exposures to ETS are often asseased using several measures as markers, including mark- ers of the vapor phase and the particulate phase as well as reactive and nonreactive constituents. Although biological markers show promise as measures of exposure because they measure the absorp- tion of smoke constituents, they too have limitations (discussed in Chapter 4). An individual’s exposure is a dynamic integration of the concentration in various environments and the time that the individual spends in those environments. In specifying an individual’s exposure to specific components of ETS, consideration must be given to the time scale of exposure appropriate for the response of interest. Immediate exposures of seconds or hours would be most relevant for irritant and acute allergic responses. Time-averaged exposures, of hours or days, may be important for acute contemporary effects such as upper and lowe: respiratory tract symptoms or infections; chronic exposures occur ring over a year or a lifetime might be associated with increasec prevalence of chronic diseases and risk of cancer. The spatial dimensions or the proximity of the individual to the source of smoke is important in assessing that individual’s exposure to ETS. ETS is a complex, dynamic system that changes rapidly once emitted from a cigarette. Physical processes such as evaporation and dilution of the particles, scavenging of vapors on surfaces, and chemical reactions of reactive compounds are continuously occurring and modify the mixture referred to as ETS. An individual located a few centimeters or a meter from a burning cigarette may be exposed to a high concentration of ETS, ranging from 200 to 300 mg/m®, and may inhale components of the mostly undiluted smoke plume and of the exhaled mainstream smoke. Ayer and Yeager (1982) reported cigarette plume concentrations of formaldehyde and acrolein in the core smoke stream emitted from the cigarette of up to 100 times higher than known irritation levels. Hirayama, as reported by Lehnert (1984), cites the importance of this “proximity effect” in assessing exposure. Distances on the order of a meter to tens of meters from a burning cigarette are relevant for exposures in offices, restaurants, a room in a house, a car, or the cabin of a commercial aircraft. At these distances, the mixing of ETS throughout the airspace and the factors that affect concentration are of importance in determining exposure for people in the space. In many rooms, mixing is not completely uniform throughout the volume, and Significant concentration gradients can be demonstrated (shizu 1980). These concentration gradients will affect an individual’s exposure by modifying the effectiveness of ventilation in diluting or removing pollutants. The airborne mass concentration may vary by 141 a factor of 10 or more within a room. Short-term measurements in rooms with smokers can yield respirable particulate concentrations of 100 to 1,000 pg/m* (Repace and Lowrey 1980). Multihour measurements average out variations in smoking, mixing, and ventilation and yield concentrations in the range of 20 to 200 g/m‘ (Spengler et al. 1981, 1985, 1986). Finally, on a systems scale, as in a house or building, concentrations are influenced by dispersion and dilution through the volume. Most time-integrated samples are taken on this larger scale. Using a piezobalance, Lebret (1985) found significant variation in respirable suspended particulate (RSP) levels between the living room, kitchen, and bedroom in homes in the Netherlands during smoking or within one-half hour of smoking. Ju and Spengler (1981) studied the room-to-room variation in 24-hour average concentra- tions of respirable particles in various residences. Although differ- ences between some rooms were statistically significant, absolute differences were relatively small, with a maximum difference of a factor of 2. Moschandreas and colleagues (1978) released sulfur hexafluoride, a tracer gas, in the living rooms of several residences and observed uniform concentrations in adjacent rooms within 30 to 90 minutes. RSP, which is slightly reactive, and nonreactive gases would be expected to rapidly migrate through adjacent rooms. Therefore, in a setting such as the work environment, where the duration of exposure is several hours or more, ETS would be. expected to disseminate throughout the airspace in which smoking is occurring. Smoke dissemination may be reduced when air exchange rates are low, as may occur when internal doors are closed. Time-Activity Patterns Individual time-activity patterns are a major determinant of exposure to ETS. The population of the United States is mobile, spending variable amounts of time in different microenvironments. Individual activity patterns depend on age, occupation, season, social class, and sex. For example, Letz and colleagues (1984) surveyed the time-activity patterns of 332 residents of Roane County, Tennessee, and found that 75 percent of the person-hours were spent at home, 10.8 percent at work, 8.5 percent in public places, 2.9 percent in travel, and 2.8 percent in various other places. As expected, Occupation and age were strong determinants of time-activity patterns. Housewives and unemployed or retired individuals spent 84.9 percent of their time at home, and occupational groups worked 21 to 24 percent of the hours. Students tended to spend the largest percentage of their time in public places, presumably schools, ranging from 14.7 percent for the youngest group to 19.17 percent for the oldest group of students. 142 TABLE 7.—Mean percent and standard deviation of time allocation in various locations by work or school classification subgroup Outdoor Office/ Industrial/ —Total, all Location Homemaker Student worker Service Construction participants Home 84.34 60.91 49.97 68.74 57.28 64.21 (2.02)! (13.92) (12.24) (8.72) (7.05) (13.99) Outside 5.52 8.62 19.81 2.47 10.59 8.08 (3.27) (6.53) (8.55) (2.49) (10.74) (7.07) Motor vehicle 4.28 5.1 8.67 4.69 1.64 5.51 (3.19) (3.74) (6.15) (2.33) (7.52) (4.29) Other indoors 6.01 23.61 21.55 24.99 24.80 21.58 (3.27) (10.62) (5.32) (10.24) (12.86) (11.87) Cooking 4.69 0.34 0.00 232 0.52 1.24 (1.88) (0.79) (0.00) (2,30) (0.86) (1.98) Near smokers 2.84 5.20 2.75 11.73 12.03 6.89 4.32) (7.88) (3.38) (15.19) (10.05) (9.71) Number 8 32 4 12 8 662 * Numbers in parentheses are the standard deviation. * Two unemployed participants were included in the total, but not given a separate category. SOURCE: Data from Quackenboss et al. (1982). The time allocations for various population subgroups in Portage, Wisconsin, are summarized in Table 7 (Quackenboss et al. 1982). The data are consistent with the findings of Letz and colleagues (1984) and show that the variability of individual nonsmokers’ exposure to smokers can be quite marked between the various occupational subgroups. Infants have unique time-activity patterns; their mobility is limited and the locations where they spend their time depend primarily on their caretakers. The time-location patterns for 46 infants is illustrated in half-hour segments in Figure 1 (Harlos et al. in press). Although infants spend most of their time in their bedrooms, they are in contact with a caretaker while traveling or in the living room or the kitchen for approximately half of the day. These infant time-activity patterns presumably correspond to the family patterns and may significantly influence the infants’ poten- tial exposure. Although most people spend approximately 90 percent of their time in just two microenvironments (home and work) (Szalai 1972), important exposures can be encountered in other environments. For instance, commuting or being “in transit” accounts for about 0.5 to 1.5 hours per day for most people. Therefore, additional information 143 24 | 22 J 20 CRS Z \ l 18 I 16 N Sis al WS y 7 ] 14 Living room LZ i AS XX J 12 Ue x Hour of the day ! 10 Bedroom ZA Other room HBB kitchen [_] outside nouse RSS Travel iH Unknown 4. | 1 3 8 & SWUBJU! JO JOQUINN 10 FIGURE 1.—Time location patterns for 46 infants SOURCE: Harlos et al. (in press). on the time spent and the ETS concentration in various microenvi- ronments may be useful in defining exposure. This exposure information can be obtained by questionnaire and validated by personal monitoring programs. The characterization of concentra- 144 tions or exposures or both in microenvironments should use time scales appropriate for the health effect of interest. These variations in location and time-activity patterns can make the reconstruction of detailed ETS exposure difficult in studies of long-term health effects. The limitations in utilizing this time-activity approach in charac- terizing exposures to other environmental pollutants also apply for ETS exposures. They include the following: the extent to which overall population estimates can be generalized to individual pat- terns is poorly understood; concentrations in various microenviron- ments are only partially characterized; the variation in time and activity patterns and their effects on concentration levels are not established; extrapolation to longer time scales either prospectively or retrospectively has not been validated; the differences within structures, i.e., room to room variations, are not well established. Temporal and Spatial Distribution of Smokers Exposure to ETS can occur in a wide variety of public and private locations. Approximately 30 percent of the U.S. adult population currently are cigarette smokers. Nationwide, 40 percent of homes have one or more smokers (Bureau of the Census 1985). In a survey of more than 10,000 children in six US. cities, the percentage of children living with one or more smoking adults varied from a low of 60 percent to a high of 75 percent (Ferris et al. 1979). Lebowitz and Burrows (1976) reported that 54 percent of children in a study in Tucson had at least one smoker in the home; Schilling and colleagues (1977) reported that 63 percent of homes in a Connecticut study had a smoker in the home. These data indicate that the population potentially exposed to ETS in the home is greater than might be inferred from aggregated national statistics on the prevalence of smoking. A variation in the percentage of homes with smokers may be observed among different regions. Furthermore, within house- holds, smoking does not take place uniformly in time or space. Smoking patterns may change with activity, location, and time of day. These variables all serve to modify a nonsmoker’s exposure to ETS. Exposure to ETS at home may also correlate with ETS exposures outside the home, possibly because nonsmokers married to smokers may have a greater tolerance for ETS-polluted environments or may be in the company of more smokers because of the spouses’ tendency to associate with other smokers. Wald and Ritchie (1984) used a biological marker and questionnaires to show that nonsmokers married to smokers reported a duration of exposure to ETS greater outside the home than was reported by nonsmokers married to nonsmokers (10.7 hours and 6.0 hours, respectively). Smoking prevalence varies widely among different groups (e.g., teenage girls, nonworking adults, and adults employed in various 145 occupations); this variation modifies the exposure of nonsmokers to ETS. Smokers are present in nearly all environments, including most workplaces, restaurants, and transit vehicles, making it almost impossible for a nonsmoker to avoid some exposure to ETS. The number of cigarettes consumed per hour by the smoker may vary at different times in the day, and the rate and density of smoking will also differ by the type of indoor environment and activity in such locales as schools, autos, planes, offices, shops, and bars. ~ Although there have been numerous measurements of ETS concentrations in various indoor settings, these data do not repre- sent a comprehensive description of the actual] distribution of ETS exposures in the U.S. population. Spengler and colleagues (1985) and Sexton and colleagues (1984) demonstrated by the personal monitor- ing of respirable particles and the use of time-activity questionnaires that exposures to ETS both at home and at work are significant contributors to personal exposures. However, additional data on the distribution of smokers in the nonsmokers’ environment, as well as the distribution of ETS levels in that environment, are needed in order to characterize the actual ETS exposure of the U.S. population. Determinations of Concentration of Environmental Tobacco Smoke Environmental tobacco smoke is a complex mixture of chemical compounds that individually may be in the particulate phase, the vapor phase, or both. ETS concentration varies with the generation rate of its tobacco-derived constituents, usually given as micrometer per hour. The generation rate for ETS has been approximated by the number of cigarettes smoked or the number of people present in a room who are actively smoking. Room-specific characteristics such as ventilation rate, decay rate, mixing rate, and room volume also modify the concentration. Because ETS particles have MMDs in the 0.2 to 0.4 4m range, convective flows dominate their movement in air, they remain airborne for long periods of time, and they are rapidly distributed through a room by advection and a variety of mixing forces. Under many conditions, the ventilation rate of a space will dominate chemical or physical removal mechanisms in deter- mining the levels of ETS particles. Nonreactive ETS components distribute rapidly through an air- space volume, and their elimination depends almost solely on the ventilation rate. For example, Wade and colleagues (1975) simulta- neously measured carbon monoxide, a nonreactive gas, and nitrogen dioxide, a reactive gas, in a house and determined their half-lives to be 2.1 and 0.6 hours, respectively. This study demonstrates the need for caution in extrapolating from one vapor phase compound to another. Reactive gases and vapors may be rapidly lost to surfaces or 146 may react with other chemical species. Their removal may be dominated by their reaction or absorption rates, Furthermore, the decay of ETS-derived substances can be a function of the chemical as well as the physical characteristics of room surfaces. For example, Walsh and colleagues (1977) found that sulfur dioxide removal was greater for rooms with neutral and alkaline carpets than for rooms having carpets with acidic pH. Reactions with furnishings and other materials may occur for some ETS components as well. Microenvironmental Measurements of Concentration As was discussed earlier, the complex chemical makeup of ETS makes the measurements of individual levels for each compound present in ETS impossible with existing resources; thus, some individual constituents have been measured as markers of overall smoke exposure. Because many of these constituents are also emitted from other sources in the environment, the contribution of ETS to the levels of these constituents is quantified by determini the enrichment of specific compounds found in smoke-polluted environments relative to the concentration measured in nonsmoking areas. Various ETS components have been measured for this purpose, including acrolein, aldehydes, aromatic hydrocarbons, carbon monoxide, nicotine, nitrogen oxides, nitrosamines, phenols, and respirable particulate matter. A summary of the levels found and the conditions of measurement are presented in Tables 8 through 15. The major limitation of using most of these gases, vapors, and particles is their lack of specificity for ETS. The presence of sources, other than tobacco smoke, of these compounds may limit their utility for determining the absolute contribution made by ETS to room concentrations. Levels of nicotine and tobacco-specific nitrosamines, however, are specific for ETS exposure. Obviously, no single measurement can completely characterize the nonsmoker’s exposure to ETS, and many studies have measured several of these components in order to characterize the exposure. Markers should be chosen both because of their accuracy in estimating exposure and because of their relevance for the health outcome of interest. One widely reported marker of ETS is respirable suspended particulate (RSP) matter. Although lacking specificity for tobacco smoke, the prevalence and number of smokers correlates well with RSP levels in homes and other enclosed areas. A study of the RSP levels in 80 homes in six cities (Figure 2) (Spengler et al. 1981) showed that indoor concentrations were higher on average and had a greater range than the outdoor concentrations. From these data, it is evident that even one smoker can significantly elevate indoor RSP levels. 147 SPT TABLE 8.—Acrolein measured under realistic conditions. Levels Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Badre et al. Cafes Varied Not given 100 mL samples 0.03-0.10 mg/m* (1978) Room 18 smokers Not given 100 mL samples 0.185 mg/m* Hospital lobby 12 to 30 smokers Not given 100 mL samples 0.02 mg/m? 2 train compartments 2 to 3 smokers Not given 100 mL samples 0.02-0.12 mg/m* Car 3 smokers Natural, open 100 mL samples 0.03 mg/m? 2 smokers Natural, closed 100 mL samples 0.30 mg/m* Fischer et al. Restaurant 50-80/470 m* Mechanical 27 x 30 min samples 7 ppb (1978) and Restaurant 60-100/440 m* Natural 29 x 30 min samples 8 ppb Weber et al. Bar 30 -40/50 m?* Natural, open 28 X 30 min samples 10 ppb (1979) Cafeteria 80-150/574 m* 11 changes/hr 24 X 30 min samples 6 ppb (6 ppb nonsmoking section) 6FT TABLE 9.—Aromatic hydrocarbons measured under realistic conditions Levels Nonsmoking controls Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range Benzene (mg/m*) Badre et al. Cafes Varied Not given 100 mL samples 0.06-0.15 (1978) Room _ 18 smokers Not given 100 mL samples 0.109 Train compartments 2 to 3 amokers Not given 100 mL samples 0.02-0.10 Car 3 smokers Natural, open 100 mL samples 0.04 2 smokers Natural, closed 100 mL samples 0.15 Toulene (mg/m* Cafes Varied Not given 100 mL samples 0.04-1.04 Room 18 smokers Not given 100 mL samples 0.215 Train compartments 2 to 3 smokers Not given 100 mL samples 1.87 Car 2 amokers Natural, closed 100 mL samples 0.50 a /m* Elliott and Rowe Arena 8,647-10,786 people Mechanical Not given ql (1975) 12,000-12,844 people Mechanical Not given 9.9 13,000-14,277 people Mechanical Not given 21.7 Separate non- 0.68 activity days Galuskinova Restaurant Not given Not given 20 days in summer 6.2 (1964) 18 days in the fall 28.2-144 OST TABLE 9.—Continued Type of Study premises Occupancy Just et al. Coffee houses Not given (1972) Perry (1973)* 14 public places Not given ''The correctness of the data is doubtful (Grimmer et al. 1977). Levels Nonsmoking controls Monitoring Ventilation conditions Mean Range Mean Range Not given 6 hr continuous 0.25-10.1 4.0-9.3 (outdoors) Benzofe ne_(ng/m*, 3.3-23.4 3.0-5.1 (outdoors) Benzofghi)peryiene (ng/m*) 5.9-10.5 6.9-13.8 (outdoors) Perylene (ng/m*)_ 0.7-1.8 0,1-1.7 (outdoors) Pyrene (ng/m') 4.1-9.4 2.8-7.0 (outdoors) Anthanthrene (ng/m* 0.6-1.9 0.5-1.8 (outdoors) Coronene (ng/m’) 0.5-1.2 1.0-2.8 Phenols (u/m’) TA-ALB Benzofalpyrene (ng/m*) _ Not given Samples, 5 outdoor < 20-760 < 20.43 locations TST TABLE 10.—Carbon monoxide measured under realistic conditions Levels (ppm) Nonsmoking controls (ppm) Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range Badre et al. 6 cafes Varied Not given 20 min samples 2-23 (outdoors) 0-15 (1978) Room 18 smokers Not given 20 min samples 60 0 (outdoors) Hospital lobby 12 to 30 smokers Not given 20 min samples 5 2 train 2 to 3 smokers Not given 20 min samples 45 compartments Car 3 smokers Natural, open 20 min samples 14 0 (outdoors) 2 smokers Natural, closed 20 min samples 20 0 (outdoors) Cano et al. Submarines 157 cigarettes Yes <40 ppm (1970) 66 m* per day 94-103 cigarettes Yes <40 ppm per day Chappell and 10 offices Not given Values not 7 xX 23 min 2.6 + 10 15-4.5 25 + 10 15-45 Parker given samples (outdoors) (1977) 15 restaurants Not given Values not 17 x 23 min 40 + 2.5 1.0-9.5 2.5 + 15 1.0-5.0 given samples (outdoors) 14 nightclubs Not given Values not 19 < 2-3 min 13.0 + 7.0 3.0-29.0 3.0 + 2.0 1.0-5.0 and taverns given samples (outdoors) Tavern Not given Artificial 16 x 2-3 min 85 samples None 2x 23 min 35 (peak) samples Offices 1440 fs Natural, open 2-3 min samples 10.0 (peak) 30 min after 1.0 amoking 6ST TABLE 10.—Continued Levels Nonsmoking controls Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range Coburn et al. Rooms Not given Not given Not given 4.3-9.0 (1965) Nonsmokers’ rooms 22 + 0.98 04-45 Cuddeback Tavern 1 10-294 people 6 changes/hr 8 hr continuous 11.5 10-12 2 (outdoors) et al. . 2 hr after smoking ~l1 : (1976) Tavern 2 Not given 1-2 changes/hr 8 hr continuous 17 ~8-22 Values not given 2 hr after amoking ~12 Values not given U.S. Dept. of 18 military 165-219 people Mechanical 6-7 hr continuous <6 Transportation planes (1971)* 8 domestic 27-113 people Mechanical 1¥%,-2%, hr <2 planes continuous Elliott and Arena 1 11,806 people Mechanical Not given 9.0 3.0 (nonactivity day) Rowe Arena 2 2,000 people Natural Not given 25.0 3.0 (nonactivity day) (1975)* Nonsmoking 9.0 arena Fischer et al. Restaurant 50-80/470 m* Mechanical 27 x % min 51 2.1-9.9 48 (outdoors) (1978) and samples Weber et al. Restaurant 60-100/440 m* Natural 29 x 30 min 2.6 1.43.4 1.5 (outdoors) (1979) samples Bar 80-40/50 m* Natural, open 28 x 30 min 48 2.4-9.6 1.7 (outdoors) samples Cafeteria 80-150/574 m* 11 changes/hr 24 X 30 min 12 0.7-L.7 0.4 (outdoors) Nonsmoking 05 0.3-0.8 room 8ST TABLE 10.—Continued Levels (ppm) Nonsmoking controls (ppm) Type of Monitoring . Study premises Occupancy Ventilation conditions Mean Range Mean Range Godin et al. Ferryboat Not given Not given 11 grab samples 18.4 + 87 3.0 + 2.4 (nonsmoking room) (1972) Theater foyer Not given Not given Grab samples 3.4 + 0.8 14 + 08 (auditorium) Harke Office ~72 m* 236 m*/hr 30 min samples “<25-48 (1974)! Office ® ~78 m? Natural 30 min samples <2.5-9.0 Harke and Car 2 smokers Natural Samples 42 (peak) (Nonsmoking runs) Peters (4 cigs) 13.5 (peak) (1974)* Mechanical Samples 32 (peak) (Nonsmoking runs) 15.0 (peak) Harmsen and Train 1-18 smokers Natural Not given 0-40 Effenberger (4957)' Perry 14 public Not given Not given One grab sample <10 (1973)* places Portheine Rooms Not given Not given Not given 5-25 (1971)" Sebben et al. 9 nightclubs Not given Varied 77 X 1 min 13.4 6.5-41.9 (1977) samples Outdoors 9.2 3.0-35.0 14 restaurants Not given Not given Spot checks 9.9 + 5.5 Values not given 45 restaurants Not given Not given Spot checks 8.2 + 2.2 7.1 + 1.7 (outdoors) 33 stores Not given Not given Spot checks 10.0 + 4.2 11.5 + 6.9 (outdoors) 3 hospital Not given Not given Spot checks 48 Values not given lobbies FST TABLE 10.—Continued Levels Nonsmoking controls Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range Seiff Intercity bus Not given 15 changes/hr, 33 ppm (1978) 23 cigarettes burning continuously 3 cigarettes 18 ppm burning continuously Slavin and 2 conference Not given 8 changes/hr Continuous, 8 (peak) 1-2 (separate Hertz rooms morning nonsmoking day) (1975) 6 changes/hr Continuous, 10 (peak) 1-2 (separate morning nonsmoking day) Szadkowski 25 offices Not given Not given Continuous 2.78 + 1.42 2.59 + 2.23 et al. (separate nonsmoking (1976) offices) ‘The Drager tube used is accurate only within + 25 percent. * The MSA Monitaire Sampler used is accurate only within + 25 percent. * Three cigarettes and one cigar smoked in 20 minutes. * About 40 cigarettes/day were smoked. * About 70 cigarettes/day were smoked. * Four filter cigarettes were smoked. * No experimental description given. SST TABLE 11.—Nicotine measured under realistic conditions 7 Nonsmoking Levels (ug/m*) controls Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range Badre et al. 6 cafes Varied Not given 50 min sample 25-52 (1978) Room 18 smokers Not given 50 min sample 500 Hospital lobby 12 to 30 smokers Not given 50 min sample 37 2 train compartments 2 to 3 smokers Not given 50 min sample 36-50 Car 3 smokers Natural, open 50 min sample Natural, closed 50 min sample 1010 Cano et al. Submarines 157 cigarettes Yes 32 pg/m* (1970) 66 m? per day 94-103 cigarettes Yes 15-35 pg/m* per day Harmsen and Train Not given Natural, closed 30-45 min 0.7-3.1 Effenberger samples (1957) / Hinds and First Train Not given Not given 2%, hr samples 49 Values not given (1975)* Bus Not given Not given 2%, hr samples 63 Values not given Bus waiting room Not given Not given 2, hr samples 10 Values not given Airline waiting room Not given Not given 2%, hr samples 3.1 Values not given Restaurant Not given Not given 2%, hr samples 5.2 Values not given Cocktail lounge Not given Not given 2, hr samples 10.3 Values not given Student lounge Not given Not given 2%, hr samples 28 Values not given Weber and Fischer 44 offices Varied Varied 140 x 3 hr 09 + 19 13.8 (peak) Values not given (1980)? samples 9ST TABLE 11.—Continued Nonsmoking Levels (ug/m') controls Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range First 1 public building Nonsmokers Mechanical Not given 5.5 (1984) 8 public buildings 1 to 5 amokers Natural and Not given 13.2 2.7-30.0 mechanical Muramatsu et al. Office Not given Not given Not given 19.4 9.3-31.6 (1984) Office Not given Not given Not given 22.1 14.6-26.1 Laboratory Not given Not given Not given 58 18-9.6 § conference rooms Not given Not given Not given 88.7 16.5-53.0 3 houses Not given Not given Not given M1 76-146 Hospital lobby Not given Not given Not given 3.0 1.8-5.0 4 hotel lobbies Not given Not given Not given 11.2 5.5-18.1 5 restaurants Not given Not given Not given 14.8 7.1-27.8 8 cafeterias Not given Not given Not given 26.4 11.6-42.2 3 bus and railway Not given Not given Not given 19.1 10.1-96.4 waiting rooms 4 cars Not given Not given Not given 417 7.1-83.1 8 trains Not given Not given Not given 16.4 8.6-26.1 7 airplanes Not given Not given Not given 15.2 6.3-28.8 ‘ Background levels have been subtracted. * Control values (unoccupied rooms) have been subtracted. LST TABLE 12.—Nitrogen oxides measured under realistic conditions Nonsmoking Levels controls (ppb) Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range Fischer et al. Restaurant 50-80/470 m* Mechanical 27 X 30 min NO,: 76 59-105 63 (outdoors) (1978) and samples NO: 120 36-218 115 (outdoors) Weber et al. Restaurant 60-100/440 m* Natural 29 x 30 min NO,: 63 24-99 50 (outdoors) (1979) samples NO: 80 14-21 11 (outdoors) Bar 30-40/50 m* Natural, 28 X 30 min NO;: 21 1-41 48 (outdoors) open samples NO: 195 66-414 44 (outdoors) Cafeteria 80-150/574 m* 11 changes/hr 24 xX 30 min NO,: 58 35-103 34 (outdoors) samples NO: 9 2-38 4 (outdoors) Other—non- NO,: 27 16-44 smokers room NO: 5 2-9 Weber and 44 offices Varied Varied 348-354 NO,: 24 + 22 115 (peak) Values not given Fischer samples (1980)! NO: 32 + 60 280 (peak) Values not given 1 Control values (unoccupied rooms) have been subtracted. Sct TABLE 13.—Nitrosamines measured under realistic conditions Levels (ng/L) Type of Monitoring Study premises Occupancy Ventilation conditions Mean Brunnemann and Train bar car Not given Mechanical 90 min continuous 0,13 Hoffmann Train bar car Not given Natural 90 min continuous 0.11 (1978) Brunnemann et al. (1978) Bar Not given Not given 3 hr continuous 0.24 Sports hall Not given Not given 3 hr continuous 0,09 Betting parlor Not given Not given 90 min continuous 0.06 Discotheque Not given Not given 2*/, br continuous 0.09 Bank Not given Not given 5 hr continuous 0.01 House Not given Not given 4 hr continuous <0.005 House Not given Not given 4 br continuous <0.003 6ST TABLE 14.—Particulates measured under realistic conditions Nonsmoking Occupancy Monitoring Levels (g/m *) controls (ug/m*) Type of {active smokers conditions Study premises per 100 m*) Ventilation (min) Mean SD Mean SD Repace and Cocktail party 0.75 Natural 15 351 + 38 24 Lowrey Lodge hall 1.26 Mechanical 50 697 + 28 6! (1980) Bar and grill 1.78 Mechanical 18 589 + 28 637 Firehouse bingo 2.77 Mechanical 16 417 + 63 51° Pizzeria 2.94 Mechanical 32 414 + 58 40° Bar/cocktail lounge 3.24 Mechanical 26 334 + 120 50! Church bingo game 0.47 Mechanical 42 279 + 18 30 Inn 0.74 Mechanical 12 239 + 9 22' Bowling alley 1.53 Mechanical 20 202 + 19 49° Hospital waiting room 2.15 Mechanical 12 187 + 652 58? Shopping plaza restaurant Sample 1 0.18 Mechanical 18 163 + 8 59! Sample 2 0.18 Mechanical 18 13 + 4 36" 3 TABLE 14—Continued Nonsmoking Occupancy Monitoring Levels (yg/m?) controls (g/m *) Type of (active smokers conditions Study premises per 100 m*) Ventilation (min) Mean SD Mean SD Barbeque restaurant 0.89 Mechanical 10 196 + 17 40} Sandwich restaurant A Smoking section 0.29 Mechanical 20 10 + 36 403 Nonsmoking section 0 Mechanical 20 b+ 6 30 Fast-food restaurant 0,42 Mechanical 40 109 + 38 um! Sports arena 0.09% Mechanical 12 4 + 18 55: Neighborhood restaurant/bar 0.40 Mechanical 12 93 + 17 55! Hotel bar 0.59 Mechanical 12 98 + 2 3% Sandwich restaurant B Smoking section 0.138 Mechanical 8 e+ 7 55 Nonsmoking section 0 Mechanical 21 51 Roadside restaurant 1.12 Mechanical (9.5 ach*) 18 107¢ 0 Conference room 3.54 Mechanical (4.3 ach*) 6 19474 55 Repace and Dinner theater 0.14 Mechanical “4 45 + 43 47 +10 Lowrey Reception hall 1.19 Mechanical 20 301 + 90 33! (1982) Bingo hall 0.93? Natural 2 1140 4: 0.932 Mechanical (1.89 ach*) 6 443¢ 40! ’ Sequential outdoor measurement (6 minute average). * Estimated. * Air changes per hour. “Equilibrium level as determined from concentration vs. time curve. TOT TABLE 14.—Continued Levels (ug/m*) Nonsmoking controis (g/m?) Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range Cuddeback et al. Tavern Not given 6 changes/hr 4x 8hr 310 233-346 (1976) continuous Tavern Not given 1-2 changes/hr 8 hr continuous 986 US. Dept. of 18 military planes 165~219 people Mechanical 72% 67 hr <10-120 Transportation samples (1971) 8 domestic planes 27-113 people Mechanical 24 xX 14-2%, hr Not given samples Dockery and Residences Not given Varied 24 hr samples 32 Spengler (1981) Elliott and Arena 1 11,806 people Mechanical During activities 323 42 (nonactivity day) Rowe Arena 2 2,000 people Natural During activities 620 92 (nonactivity day) (1975) Arena 8 (smoking 11,000 people Mechanical During activities _ 148 71 (nonactivity day) prohibited) Harmsen and Trains 15-120 people Natural Not given 46-440 Effenberger particles/cm* (1957) Nonsmokers’ cars 20-75 particles/cm* Just et al. 4 coffee houses Not given Not given 6 hr averages 1160 500-1900 570 (outdoors) 100-1900 (1972) Neal et al. Hospital unit Not given Mechanical 48 hr samples 21+ 14 3-58 73 + 25 (1978) Hospital unit Not given Mechanical 48 hr samples 40 + 21 13-79 72 + 25 cot TABLE 14,— Continued Levels (ug/m?) Nonsmoking controls (yg/m*) Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean Range Spengler et al. Residences 2+ smokers Natural 24 hr samples 70 + 43 21 + 12 (outdoors) (1981) 1 smoker Natural 24 hr samples 37 + 15 21 + 12 (outdoors) Weber and 44 offices Varied Natural and 429 x 2 min 133 + 130! 962 (peak) Fischer (1980) mechanical - samples Quant et al. Office No. 1 0.82? Mechanical Five 10-hr. workday 45 39-54 5-15 (1982) Office No. 2 0.68? Mechanical averages; continuous 46 37-50 15-20 Office No. 3 1.46* Mechanical monitoring 68 42-89 15-20 Brunekreef and 26 houses 1 to 3 smokers Natural 2 mo averages 153* 60-340 55 20-90 Boleij (1982) First 1 public building Nonsmokers Mechanical 2 min 20 (1984) 8 public buildings 1 te 5 smokers Natural and 2 min 260 40-660 mechanical Hawthorne et al. 11 residences Nonsmokers 0.18-0.96 6-15 min 940 (1984) 8 residences Nonsmokers 0.26-1.98 _ 5-15 min 12-46 2 residences Smokers 0,27-1.47., 5-15 min 96-106 Nitechke et al. Outdoor 168 hr 11 11-28 (1985) 19 residences Nonsmokers Natural 168 hr 26 6-88 11 residences Smokers Natural 168 hr 59 10-144 Spengler et al. | Outdoor 24 br 18 (1985) 73 residences Nonsmokers Natural 24 br 28 24 residences Smokers Natural 24 hr 74 Sterling and 1 office Smokers Not given Not given 26 15-36 Sterling 22 offices Smokers Not given Not given 32 (1984) * Values above background. * Habitual smokers per 100 m?. * Weighted mean. egt TABLE 15.—Residuals measured under realistic conditions Nonsmoking Leveis controls Type of Monitoring Study premises Occupancy Ventilation conditions Mean Range Mean = Range Acetone (mg/m*) Badre et al. 6 cafes Varied Not given 100 mL samples 0.91-5.88 (1978)! Room 18 smokers Not given 100 mL samples 051 Hospital lobby 12 to 30 smokers Not given 100 mL samples 1.16 2 train 2 or 3 smokers Not given 100 mL samples 0.36-0.75 compartments Car 3 smokers Natural, open 100 mL samples 0.32 Car 2 smokers Natural, closed 100 mL samples 1.20 Sulfates (ug/m*) Dockery and Residences Not given Varied 24 hr samples 4.81 Spengler (1981) Sulfur dioxide (ppb) Fischer et al. Restaurant 50-80/470 m* Mechanical 27 x 30 min samples 20 9-32 12 ppb (1978) Restaurant 60-100/440 m* Natural 29 x 30 min samples 13 5-18 6 Bar 30-40/50 m* Natural, open 28 x 30 min samples 30 13-75 8 Cafeteria 80-150/574 m* 11 ch/hr 24 x 30 min samples 15 1-27 12 Other nonsmokers’ 7 3-13 room Aldehydes (ug/m*) Just et al. 4 coffee houses Not given Not given 6 hr continuous 12.0-15.3 (1972) ‘ See original paper for nine other residuals. SOURCE: Sterling et al. (1982). wn ee = Outdoor ~-=~ = Indoor. no smokers 120 wom = Indoor, 1 smoker J ——. = Indoor, > 1 smoker pg/m? Respirable suspended particulate matter Op TT Nov. Dec. Jan. Feb. Mar. Apr. May Jun. Jul. Aug. Sep. Oct. Nov. Dac. Jan. Feb. Mar. Apr. 1976 1977 1978 FIGURE 2.—Monthly mean mass respirable particulate concentrations (ug/m*) across six cities SOURCE: Spengler et al. (1981). TABLE 16.—Respirable particulate levels as a function of number of smokers Smoker status Number Mean (ug/m*) Standard deviation No smokers 35 homes/1,186 samples 24.4 11.6 1 smoker 15 homes/494 samples 36.5 14.5 2 smokers 5 homes/153 samples 10.4 429 2+ smokers 4 homes/? samples 518 12.3 SOURCE: Spengler et al. (1981). Spengler and colleagues (1981) collected respirable suspended particulate samples in 55 homes in six cities. The average concentra- tions observed between May 1977 and April 1978 are shown in Table 16. The quantity of tobacco smoked was not reported, nor was the number of hours each smoker spent in the home. The researchers concluded that the mean RSP levels increased by 20 pg/m* per smoker. Dockery and Spengler (1981) further analyzed these data and considered the number of cigarettes smoked in the home. They concluded that the mean RSP concentration increased by 0.88 g/m? 164 for every cigarette smoked per day in the house. A one-pack-a-day smoker in the home thus raises indoor respirable particulate levels by 17.6 pg/m*. Air conditioning increased the contribution of each cigarette by 1.23 yg/m%, to a total of 2.11 yg/m® per cigarette in fully air-conditioned homes. These values are annual averages; air-condi- tioned homes, in which air is recirculated during the warmer months, have higher levels. Repace and Lowrey (1980) measured RSP concentration using a piezobalance in several public and private locations, including restaurants, cocktail lounges, and halls, in both the presence and the absence of smoking. They then developed an empirical model utilizing the mass-balance equation. Using both measured and estimated parameters as input to the model, they validated the model for predicting an individual’s exposure to the RSP constituent of ETS. The model takes the form: Ce, = 650 D,/nv; where Ceq equals the equilibrium concentration of the RSP component of ETS (ug/m'), D, equals the density of active smokers (number of burning cigarettes per 100 m*), and nv equals the ventilation rate (in air changes per hour). The ventilation rate is a complex parameter that takes into account all the room-specific constants affecting the removal of ETS, such as ventilation, decay, and mixing. Measurements in a large number of locations using measures of smoke generation such as the number of people smoking or the number of cigarettes being smoked have shown a definite relation- ship of smoke generation to particulate levels. First (1984) cautioned against the use of RSP measurements as a measure of ETS in public places because of its nonspecificity for ETS, and noted that other sources may contribute enough to the levels to invalidate the determination of the ETS contribution. However, there are few other sources of RSP in most U.S. homes, and therefore, the relationships of RSP measurements to ETS levels are generally quite accurate in this setting. Nicotine appears to be a promising tracer for ETS because of its specificity for tobacco and its presence in relatively high concentra- tions in tobacco smoke. It can also be measured in biological fluids to provide an indication of acute exposure to tobacco smoke. Cotinine, nicotine’s major metabolite, can be used as an indicator of more chronic exposure. These biological markers are discussed in a separate chapter of this Report.. Recent studies have indicated that nicotine may be primarily associated with the vapor phase of ETS and therefore not a surrogate for the particulate phase as once thought (Eudy et al. 1986). However, the possible usefulness of this compound in estimating exposure to ETS warrants further evalu- ation. The nicotine content of sidestream smoke does not differ significantly from brand to brand when normalized on a per gram of tobacco basis (Rickert et al. 1984). The use of nicotine as a marker for 165 ETS must also give consideration to its loss to surfaces and its subsequent revolatilization and readmission to the room volume. Carbon monoxide, a marker for gas phase components, has been measured extensively as a surrogate for ETS. There are many sources of carbon monoxide other than cigarettes, indoors (e.g., stoves, grills) and outdoors (e.g., automobile). This nonspecificity for ETS seriously limits its usefulness for environmental measurements. In summary, no single compound definitively characterizes an individual’s exposure to ETS. Additional research is currently under way to quantify the relationships among various constituents and ETS levels. Because of the complex nature of ETS, investigators may need to measure several markers or to separately record source variables (such as number of cigarettes smoked) in order to estimate exposure to ETS. Monitoring Studies Personal monitors can measure the concentrations of ETS in an individual’s breathing zone. Personal monitoring is preferable to area monitoring because it integrates the temporal and spatial dimensions of an individual’s exposures. At the present time, all of the studies that have used personal monitors to measure ETS constituents have utilized active samplers that provide integrated exposures over differing time periods. The markers assessed in personal monitoring studies have the same lack of specificity found in area monitoring studies. However, in many of the personal monitoring studies, time-activity diaries were kept to permit greater resolution in attributing exposure to specific sources. In Topeka, Kansas, 45 nonsmoking adults carried personal RSP monitors for 18 days, and area monitors were placed inside and outside their homes (Spengler and Tosteson 1981). The indoor RSP levels were consistently higher than outdoor levels, and the personal exposures levels were higher than either. The group was divided into those who reported ETS exposure and those who did not (Figure 3). Reported exposure to ETS clearly shifts the distribution to the right. On the average, reported ETS exposure increased an individual’s personal concentration by 20 pg/m*. Personal RSP monitors were carried by 101 nonsmoking volun- teers for 3 days in Kingston-Harriman, Tennessee (Spengler et al. 1985). The study population was divided into two groups: those who lived with a smoker and those who did not. ETS exposure was reported by 28 of the participants, with the remaining participants reporting none. The RSP distribution for the ambient samples is shown in Figure 4. Clearly, exposure to ETS significantly increases an individual’s personal concentration profile. 166 20 + _ 18 +4 16 Non-smoke-exposed 14 12 — 10 +4 Percentage 84 64 4+ 1 on. a - 0 5 10 18 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 Smoke-exposed Percentage no & DD @ oll |[lnann...| oO 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 FIGURE 3.—Percentage distribution of personal respirable particulate concentrations, non-smoke-exposed and smoke-exposed samples, Topeka, Kansas SOURCE: Spengler and Tosteson (1981). Sexton and colleagues (1984) monitored personal RSP exposure for 48 nonsmokers in Waterbury, Vermont, every other day for 2 weeks. The participants kept activity logs and had simultaneous indoor and outdoor RSP samples collected at their homes. The proportion of time individuals spent exposed to ETS was the single most important determinant of their personal exposure. Volunteers who reported greater than 120 minutes of exposure to ETS had a mean RSP exposure of 50.1 pg/m*, whereas those volunteers who reported no exposure to ETS had a mean exposure of 31.7 pg/m°. 167 100 ~ ee Te _——— =e f ae S ser } c c j Jj S 6o- 1 J a” & ' f o ? o 2 = : 4 en 2 (if a wey if - t s/f in| l I t \ 0 40 80 120 160 200 240 Respirable particulate concentration (yg/m?) FIGURE 4.—Cumulative frequency distributions of central site ambient and personal smoke-exposed and non-smoke-exposed. respirable suspended particulate concentrations SOURCE: Spengler et al. (1980). Nicotine, a tobacco-specific compound, should make an excellent tracer for ETS if its usage can be properly validated. Some considerations in its usage are detailed in the section on area sampling. Currently, no published reports are available that utilize this compound for the type of detailed personal monitoring studies carried out for RSP. However, a lightweight personal nicotine monitor has recently been developed (Muramatsu et al. 1984) that may aid this type of research. The researchers measured average nicotine concentrations ranging from 3.0 pg/m? in a hospital lobby to 38.7 pg/m* in a conference room and 47.7 pg/m* in an automobile. No information on the duration of exposure or representativeness of these levels to the general population was given. However, this study does provide information as to the range of exposures an individual may encounter and demonstrates that high nicotine levels can be encountered in various settings. It will be necessary to quantify the relationship between nicotine, a vapor phase component of ETS, and other components of interest such as RSP in order to fully utilize this tracer. Certain organic gases have been measured as possible indicators of ETS exposure or of specific effects such as irritation. These include formaldehyde and acrolein (Weber and Fischer 1980) and aromatic compounds such as benzene, toluene, xylene, and styrene (Higgins et al. 1983). The U.S. Environmental Protection Agency’s recent TEAM study utilized personal monitors, employing Tenax cartridges, to develop profiles of individual exposures to volatile organics (Wallace 168 et al. in press). The TEAM study has found significantly increased exposure to benzene for individuals exposed to ETS. Again, the nonspecificity of these materials for ETS limits their applicability. Other materials such as carbon monoxide and nitrogen dioxide have been measured in personal monitoring studies attempting to assess individuals’ exposure to ETS. Their nonspecificity and lack of sensitivity for low-level ETS exposure make them inappropriate for population-based studies. Personal monitoring techniques are currently available that will allow the assessment of individual exposures to various components of ETS. Although not widely used in the past, they can provide valuable input in developing exposure models and in validating other monitoring schemes. Their usefulness is primarily that they sample all of the microenvironments in which individuals find themselves and therefore automatically compensate for the nonuni- form temporal and spatial distributions of ETS that affect individual exposure profiles. Conclusions 1. Undiluted sidestream smoke is characterized by significantly higher concentrations of many of the toxic and carcinogenic compounds found in mainstream smoke, including ammonia, volatile amines, volatile nitrosamines, certain nicotine decom- position products, and aromatic amines. 2. Environmental tobacco smoke can be a substantial contributor to the level of indoor air pollution concentrations of respirable particles, benzene, acrolein, N-nitrosamine, pyrene, and carbon monoxide. ETS is: the only source of nicotine and some N- nitrosamine compounds in the general environment. 3. Measured exposures to respirable suspended particulates are higher for nonsmokers who report exposure to environmental tobacco smoke. Exposures to ETS occur widely in the non- smoking population. 4. The small particle size of environmental tobacco smoke places it in the diffusion-controlled regime of movement in air for deposition and removal mechanisms. Because these submicron particles will follow air streams, convective currents will dominate and the distribution of ETS will occur rapidly through the volume of a room. 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New York, Academic Press, 1967. 176 CHAPTER 4 DEPOSITION AND ABSORPTION OF TOBACCO SMOKE CONSTITUENTS CONTENTS Introduction Deposition Size Distribution of Cigarette Smoke Mainstream Smoke Sidestream Smoke Particle Deposition in the Respiratory Tract Total Deposition Regional Deposition Respiratory Tract Dose of Environmental Tobacco Smoke Cigarette Smoke Particulate Mass Deposited The Concept of “Cigarette Equivalents” Markers of Absorption Carbon Monoxide Thiocyanate Nicotine Cotinine Urinary Mutagenicity Populations in Which Exposure Has Been Demonstrated Experimental Studies Nonexperimental Exposures Quantification of Absorption Evidence of Absorption in Different Populations Quantification of Exposure Comparison of Absorption From Environmental Tobacco Smoke and From Active Smoking Conclusions References 179 Introduction the deposition of environmental tobacco smoke in the respiratory tract (Jarvis et al. 1983). However, cigarette smoke particles probably behave in a manner similar to other inhaled particles. In contrast, there are a number of observations of different markers in the biological fluids of smokers and nonsmokers. This review begins with a discussion of particle deposition in general and the factors that affect deposition. This understanding is then applied to the existing data on tobacco smoke deposition in the human respiratory tract. Subsequently, a variety of biologic markers of smoke absorp- tion are examined, and the levels of these markers found in smokers and nonsmokers under a variety of circumstances are presented. Finally, an attempt is made to quantitate the exposure of nonsmok- ers relative to that of active smokers using levels of these biologic markers. Deposition The term “deposition” refers to the transfer of a particle from inhaled air to the surface of any portion of the respiratory tract, from nose to alveolus. “Retention” is the quantity of deposited material remaining in the respiratory tract at a specified time following deposition. Retention decreases as clearance mechanisms such as mucociliary action and absorption reduce the respiratory tract burden of inhaled particles. Retention is not discussed in this review. An aerosol is a suspension of particles in a gaseous or vapor medium; cigarette smoke is an aerosol. Aerosols are characterized by such terms as mass median diameter (MMD), the diameter below which lies one-half of the particles by mass, and count median diameter (CMD), the diameter below which lies one-half of the particles by number. Most naturally occurring aerosols have a log- normal size distribution, and the magnitude of the spread of particle size is the geometric standard deviation (GSD). Particle mass is a function of the cube of the diameter; a particle with a diameter of 0.5 um has one one-thousandth of the mass of a 5 um particle. Thus, for an aerosol with a large geometric standard deviation, the mass 181 median diameter may be considerably greater than the count median diameter. The smaller particles of an aerosol, despite their relatively small mass, have a large total surface area because of their great number. A monodisperse aerosol has particles of one size, with CMD equal to MMD, and a GSD of 1. For practical purposes, a GSD of 1.2 or less is accepted as monodisperse. Most naturally occurring aerosols are polydisperse, with GSDs in the 2 range. A lognormally distributed aerosol with a GSD of 2 and a CMD of 0.1 will have an MMD of 0.42. In this discussion, when size is referred to, it is the MMD unless otherwise stated. Both the total deposition and the -deposition site in the respiratory tract vary substantially with particle size. Size Distribution of Cigarette Smoke Mainstream Smoke The size distribution of cigarette smoke has been of interest to investigators for many years. The important relationship between size and respiratory tract deposition is discussed below. Most studies have been performed using mainstream smoke. Mainstream smoke is the smoke exiting from the butt of the cigarette during puff- drawing, and sidestream smoke is the smoke plume that drifts into the environment from the burning tip of a cigarette between pufis. Environmental tobacco smoke (ETS) is the ambient burden of sidestream smoke and the smoke exhaled by a smoker. Involuntary smoking is the consumption of ETS by people, either smokers or nonsmokers, from the environment. One purpose in discussing the size distribution and respiratory tract deposition of particles is to illustrate the discrepancy between the measured particle size of mainstream smoke and its measured deposition in the human respiratory tract. The deposition fraction of mainstream smoke is several times higher than would be predicted on the basis of its particulate size. The measured deposition of sidestream smoke is more in keeping with its measured size (Hiller, McCusker et al. 1982). The standard laboratory smoke-generation technique is to force air through the cigarette as would be done by a smoker, followed by the rapid dilution of the resulting mainstream smoke so that particle size can be measured. A standard 35 cm’, 2-second puff is usually used, although actual puff volume was shown to average 45 cm* in one study (Mitchell 1962) and 56 cm? in another; for individuals, the puff Jolume can vary from 20 to 30 cm up to 70 to 80 cm’ (Hinds et The size distribution of the diluted mainstream smoke aerosol is then measured by one of a variety of techniques such as light scattering devices, microscopic measurement, or impactor collecting 182 devices. Using various diluting and sizing techniques, particle siz. measurements of mainstream cigarette smoke have been reportea from many laboratories (Table 1). One potential cause of error in have a chemical composition different from that of larger particles (Stéber 1984), possibly because of the large surface area of smaller particles. Laboratory methods, such as rapid dilution, commonly used to study mainstream smoke, are highly artificial and may not accurate- ly duplicate the generation, dilution, and inhalation of mainstream smoke by the smoker. Smoking technique and respiratory tract conditions may promote changes in particle size. Therefore, the particulate sizes in the respiratory tract may differ from the sizes measured when mainstream smoke is diluted for size analysis or when diluted sidestream smoke igs inhaled by the involuntary smoker. The smoker's puff is taken as a bolus in a relatively small volume of air into the humid upper respiratory tract. Smoking techniques vary widely (Griffiths and Henningfield 1982) and have been shown to vary significantly among groups classified as healthy smokers compared with those with emphysema and also between those with emphysema and those with bronchogenic carcinoma and bronchitis (Medici et al. 1985). Some smokers hold the puff in the mouth for several seconds prior to deep inhalation. The initial puff is highly concentrated, with approximately 10° particles/cm?, At this concentration, particle coagulation can occur rapidly, causing a tenfold to a hundredfold reduction in particle number and an increase in particle size (Hinds 1982). Also, the accumulation of water in or on the particles in the high humidity of the respiratory tract can increase particle diameter (Muir 1974), and may increase the diameter as much as 30 percent (Mitchell 1962). Some evidence suggests, however, that at least for dilute cigarette smoke, hygro- scopic growth occurs only under supersaturated conditions (Kousaka et al. 1982). Coagulation and water uptake by particles in the respiratory tract may considerably alter particle size distributions so that measurements under laboratory conditions probably do not 183 Study Size (um), concentration [no. particles/cm*} TABLE 1.—Size distribution of mainstream tobacco smoke (1974) Dilution Method Comment Wells and Gerke CMD 0.27 Not given Oscillation amplitude (1919) Sinclair CMD 0.0-0.3 fresh Light scattering Aged: size increase attributed to (1950) CMD 0.4-0.5 aged water accumulation DallaValle et al. 0.1-0.25 Not given Electrostatic separation (1954) Langer and Fisher CMD 0.5 filter 143:1 Microscopic impinger Compared with electrostatic (1956) CMD 0.6 plain collection precipitation [2-5 x 10°} GSD 1.75 Keith and Derrick CMD 0.23 296:1 Aerosol centrifuge GSD 1.64 (1960) MMD 0.45 Microscopic Calculated Porstendirfer and CMD 0.22 100,000:1 Related rate of deposition Also measured deposition Schraub (1972) [5-7 x 10°] of radioactive decay products onto particles to particle size Porstendirfer CMD 0.42 10:1 Radon daughter attached (1973) CMD 0.22 3,100:1 and deposited in spiral centrifuge -Okada and CMD 0.18 1,500:1 Light scattering GSD 1.48 Matsunuma MMD 0.29 SsT TABLE 1.—Continued Size (um), concentration Study {no. particles/cm*} Dilution Method Comment Hinds MMD 0.38-0.52 10:1-700:1 Aerosol centrifuge Size distribution decreases as (1978) CMD 0.4 10:1 dilution increases CMD 0.27 3,100:1 GSD 1.3-1.5 McCusker et al. MMD 0.29-4.3 126,000:1 Laser doppler velocimetry Aerodynamic diameter GSD 1.4 (1982) (4.2 x 10°] Chang et al. CMD 0.24-0.26 6:1-18:1 Electrical aerosol analyzer Bimodal distribution : (1984) (3.6 x 10°} (EAA) Primary mode (EAA) GSD 1.18 MMD 5.5 secondary 1-8 x 10° Anderson Cascade Impactor Second mode (CI) 5%-30% of mode (cl) total mass NOTE: CMD = count median diameter; MMD = mass median diameter; GSD = geometric standard deviation. TABLE 2.—Size distribution of sidestream tobacco smoke Study Size (um) Dilution Method Comment Keith and CMD 0.15 295:1 Aerosol Nature of sidestream Derrick Centrifuge centrifuge smoke generation (1960) process makes difficult exact determination of concentration at generation and dilution Porstendérfer CMD 0.24 Not given Related rate of and Schraub deposition of (1972) radioactive decay products onto particles to particle size Hiller, CMD 0.31 Not given Laser doppler GSD 16 McCusker et al. velocimetry (1982) NOTE: CMD = count median diameter; GSD = gi tri dard d represent distributions found in actual mainstream smoking condi- tions. Sidestream Smoke Sidestream smoke is generated by cigarettes burning spontaneous- ly between puffs and is quantitatively the major contributor to ETS. Fifty-five percent of the tobacco in a cigarette is burned between puffs, forming sidestream smoke (see Chapter 3). Dilution takes place as smoke rises in the ambient air currents. This dilution with air reduces, but probably does not eliminate entirely, the coagulation that causes the particulate to increase in size, as they may in the highly concentrated state that occurs when a smoker draws a puff of mainstream smoke into the mouth and holds it briefly before inhalation. The size distribution of sidestream smoke might be expected to resemble that of diluted mainstream smoke. The results of several reports of sidestream smoke size measurements (Table 2) support this impression. Particle Deposition in the Respiratory Tract Total Deposition Total deposition has been studied both theoretically and experi- mentally. Mathematical equations can be used to predict deposition by combining mathematical models of lung anatomy with equations describing the behavior of particles in tubes. The major property to be considered is particle size and its influence on impaction, sedimentation, and diffusion. Inertial impaction is the mechanism 186 The effect of gravity on suspended particles causes them to fall, a process called sedimentation, which also becomes relatively unim- portant for particles less than 0.5 um in size. Larger particles fall faster, and for all particles, the greater the residence time (in the lung) the greater the likelihood of deposition by sedimentation. Diffusion is the net transport of particles caused by Brownian motion. It becomes increasingly important for particles less than 0.5 um in size (Hinds 1982). The mass median diameter of sidestream smoke is in the 0.3 to 0.5 um size range. Total deposition for inhaled particles is in the 10 to 30 percent range for 0.5 wm sized particles. In Figure 1, Lippmann’s review (1977) of the measurements of total deposition of monodisperse aerosols in human subjects is modified to include more recent data and data on ultrafine particle deposition. The respiratory pattern clearly affects particle deposition. Most important for all particles, including environmental tobacco smoke, is the residence time in the lung. Deposition increases with slow deep inspiration (Altshuler et al. 1957) and with breath holding (Palmes et al. 1966; Anderson and Hiller 1985). In hamsters, the deposition of 0.38 ym particles rises in a nearly linear fashion with oxygen consumption (Harbison and Brain 1983). These data indicate that deposition of ETS during involuntary smoking increases with the increasing activity level of the exposed individual. The presence of an electrical charge on particles may increase deposition. Mainstream smoke is highly charged (Corn 1974). The addition of either a positive charge or a negative charge to inhaled particles increases deposition in animals (Fraser 1966), and neutral- ization of the charge reduces deposition 21 percent in rats (Ferin et al. 1983). There is little information describing the effect of a charge on the deposition of either mainstream or sidestream smoke in human subjects. Particle growth by water absorption may affect deposition. Mathe- -matical models that describe the effect of humidity on. particle growth indicate the potential for a considerable change in size of some particles during transit in the humid re “iratory tract (Ferron 1977; Cocks and Fernando 1982; Renninger et al. 1981; Martonen and Patel 1981) and that these changes could significantly alter deposition (Ferron 1977). Growth of 0.4 to 0.5 pm particles should increase their deposition fraction, but growth of a 0.07 Lm particle to 0.1 um, for example, would reduce its deposition (see Figure 1). Such 187 1.0 T T T T | 0.9 + © Lippeaana (1977) 0.8 > Muir and Davies (1967) T 0.7 it 06 F Hayder a al. (1974) =~ ~ Hayder ot al. (1973) @ Mastens & Jacobi (1974) > Lever (1974) ‘J Hiller, Maumder wal. (1987) © Th and Keudeon (1084) © Wiles ot al. (1988) S Schiller 0 al. (1906) 4 edie m oa L i 0.3 I q " 0.1 [- 0 1 I 1 J 1 at po sp id 4 et a 0.01 0.02 0.03 0.05 0.1 02 039 O85 0.7 1.0 2 3 5§ 7 10 20 Aerodynamic diameter~zm Figure 1.—Total respiratory tract deposition of inhaled inert particles during oral inhalation NOTE: The portion of the figure from 0.01 to 0.1 um was added to a previously published illustration of total deposition (Lippmann 1977), sources for both are indicated. The original and the additions together encompass the complete amoke particle size range. an effect has been shown for laboratory-generated aerosols in human subjects (Blanchard and Willeke 1983; Tu and Knudson 1984). While hygroscopic growth has been postulated for tobacco smoke (Muir 1974), it has been demonstrated in the laboratory to occur, at least for dilute smoke, only in supersaturated conditions (Kousaka et al. 1982). Many reports describe measured deposition of mainstream ciga- rette smoke in the human respiratory tract (Table 3). Although few studies of total sidestream smoke deposition are available, those few (Table 3) suggest that sidestream smoke does indeed deposit in a manner similar to that found for laboratory-designed research aerosols. The deposition fraction of mainstream smoke diluted 1:30 and inhaled by rats from chamber air containing 1.68 mg/L (assuming a rat tidal volume of 1.5 mL and a respiratory rate of 85) is 188 8.1 percent (Binns et al. 1978), Deposition for the sidestream smoke has been measured in mouth-breathing human volunteers at 11 percent, similar to that for similarly sized polystyrene latex spheres (Hiller, Mazumder et al. 1982). Environmental tobacco smoke exposure frequently occurs with breathing through the nose rather than through the mouth, but inert particles in the size range of ETS (0.2 to 0.4 pm) are not substanti y reduced in number by passage through the nose. The fraction of inert 0.2 um particles deposited in the alveolar region of the lung is similar for mouth breathing and nasal breathing (Raabe 1984). It is possible that the charged or reactive particles of ETS may behave somewhat differently than inert particles, but it seems unlikely that nasal breathing substan- tially alters the deposition of the small particles of ETS in comparison with mouth breathing. Regional Deposition Total deposition is subdivided into the fractions depositing in the upper respiratory tract (larynx and above), the tracheobronchial region (trachea to and including terminal bronchioles), and the pulmonary region (respiratory bronchioles and beyond) (Figure 2). Deposition in these areas is referred to as regional deposition. Particle size is a major determinant of both total and regional deposition. A mathematical model prediction of regional deposition of polydisperse aerosols is shown in Figure 2 (CRP 1966). Experimental verification of mathemati models of regional deposition is limited. Using isotope-labeled particles, it is possible to quantitate the upper respiratory tract deposition as a fraction of total deposition. By assuming that the aerosol depositing in the tracheobronchial region will be cleared within 24 hours, it is possible to measure alveolar deposition as the fraction of the total initial deposition below the larynx that is remaining at 24 hours and tracheobronchial deposition as the difference between the initial deposition and what is remaining at 24 hours. Using this method, the deposition of 3.5 um particles was this: total deposition, 0.79; upper respiratory tract, 0.10; tracheobronchial region, 0.24; and pulmonary region (alveolar), 0.45 (Emmett et al. 1982). These measurements are below the estimated regional deposition for upper respiratory tract deposition and higher for the pulmonary deposition than are the measurements calculated by using the Task Group on Lung Dynam- ics model (ICRP 1966). The regional deposition of mainstream cigarette smoke in smokers has also been studied. Subjects inhaled smoke from cigarettes labeled with radioactive 1-iodohexadecane (Black and Pritchard 1984; Pritchard and Black 1984). The results indicate that less than 40 percent of the particulate mass deposited in the pulmonary region, compared with an expected 90 percent deposition in the 189 _ TABLE 3,—Respiratory tract deposition of mainstream and sidestream cigarette smunc Puff volume Puff time Study Deposition fraction (mL) (second) Smoke dilution Respiratory pattern Mainstream smoke Baumberger 88% Not given Not given None Inhalation (1923) Schmahl et al. 98% (1954) Polydorova (1961) 80% None Usual spontaneous (22-89 range) smoking pattern Mitchell (1962) 82% 45 + 9.8 SD 19 + 0.6 SD 300:1 “Deep inhalation” (70-90 range) (33-65 range) Dalhamn et al. 96% + 3.1% SD 35 2 None Pretrained (1968) (86-99 range) standardized pattern (not described) Hinds et al. 41% 53 None Usual spontaneous (1983) (22-75 range) smoking pattern Sidestream smoke __ Binns et al. 8% Not applicable 30:1 Spontaneous (rata) (1978) (in chamber) Hiller, McCusker 11% Not applicable 50-100 pg/m* 1 L tidal volume, 12 et al. (1982) breaths/min 0.70 0.60 Pulmonary Deposition fraction f=] 3 0.10 t 7 e vr v 0.01 = 0.05 0.1 0.5 1.0 5 10 50 100 Mass median diameter, um Figure 2.—Regional deposition of particles inhaled during nasal breathing, as predicted using the deposition model proposed by the Task Group on Lung Dynamics SOURCE: Internati tection, Task Force on Lung Dynamics (1966). pulmonary region for 0.5 m particles, the size reported for cigarette smoke (Table 1). This finding further supports the concept that mainstream smoke particles increase in size in the respiratory tract by coagulation, hygroscopic growth, or both, and that this growth affects total and regional deposition. The same group studied the effect of switching the tar content of cigarettes on regional deposi- tion. Using cigarettes with between 16 and 17 mg tar, extrathoracic deposition was found to be 14 percent of the total deposition and intrathoracic deposition to be 86 percent, with 51 percent in the tracheobronchial area and 35 percent in the pulmonary region (Pritchard and Black 1984). After switching to cigarettes with between 8 and 9 mg tar, total deposition was 74 percent of that measured from cigarettes with the higher tar content, the extratho- racic deposition was unchanged, the tracheobronchial deposition was from 34 to 42 percent, and the pulmonary deposition was 18 to 25 percent of the total mass deposited with the higher tar cigarettes. With the use of mathematical deposition modeling, the observed deposition pattern was consistent with one predicted for an aerosol with an MMD of 6.5 im, more than 10 times greater than the MMD described for cigarette smoke (Black and Pritchard 1984). The deposition of particles is probably not uniform within a lung region. The mass deposited in the airways, for instance, may vary 191 widely. Enhanced deposition at specific anatomic sites may be especially important for some inhalants. For example, the concentra- tion of carcinogenic substances at a site may favor that site for cancer development. This may be especially important for cigarette smoke, since lung cancer may occur at sites of high deposition such as airway bifurcations. Deposition of a 0.3 pm laboratory-generated stable aerosol has been shown to favor right upper lobe deposition, and on the basis of surface density of deposition, the lobar bronchi (Schlesinger and Lippmann 1978). The deposition per airway genera- tion has been calculated for large particles, but has not received sufficient attention for particles in the size range of mainstream or sidestream smoke. A deposition peak has been predicted, using a lung model for the fourth airway generation (trachea is 0) for 5 pm particles, and a peak in airway surface concentration density was predicted for 8 pm particles at the fourth generation (Gerrity et al. 1979). Both of these deposition peaks are calculated for particles substantially larger than those of cigarette smoke. Depositions may be quite nonuniform even within a single airway generation. An enhanced deposition at bifurcations with highly concentrated deposition on carina ridges within bifurcations has been demonstrated in a five airway generation model of the human respiratory tract for both cigarette smoke (Martonen and Lowe 1983a) and research aerosols (Martonen and Lowe 1983p). Epidemiological studies of the pathophysiologic consequences of involuntary smoking have emphasized, among other things, an increase in the incidence of respiratory illness in children (see Chapter 2). The issue of the respiratory tract deposition of particles in children has been addressed only recently. Using morphometric measurements from casts of the lungs of children and young adults aged 11 days to 21 years, a mathematical growth model was created. Using this model and conventional methods for predicting the behavior of particles in tubes, the deposition of particles at various ages can be predicted. On the basis of these calculations, tracheo- bronchial depositions per kilogram of body weight for 5 pm particles was estimated to be six times higher in the resting newborn than ina resting adult (Phalen et al. 1985). Differences are predicted also for particles the size of sidestream smoke, with tracheobronchial deposition in infancy being twofold to threefold higher in adulthood. Total deposition has also been estimated using mathematical model- ing, with the total deposition estimated at approximately 15 percent at age 6 months and at 10 percent in adults (Xu and Yu 1986). 192 Respiratory Tract Dose of Environmental Tobacco Smoke Cigarette Smoke Particulate Mass Deposited The dose of environmental tobacco smoke to the respiratory tract is the product of the mass in inhaled air and the deposition fraction. To this point, particle size and deposition fraction, which is related to both size and respiratory pattern as well as to other less understood factors such as particle charge and hygroscopicity, have been addressed. To estimate dose, the content of smoke in inhaled air must be known, as well as the respired minute volume. Mass content in inhaled air varies widely, as does minute volume, which depends considerably on activity level. Sidestream smoke concentrations have been raised as high as 16.5 mg/m° in experimental chambers (Hoegg 1972). High levels, 2 to 4 mg/m’, have also been estimated using measured carbon monoxide concentrations for rooms 140 m? in size containing 50 to 70 persons (Bridge and Corn 1972). Such levels far exceed the EPA air quality standards for total suspended particulate of 75 yg/m* annual average and the 260 pg/m?* 24-hour average in the United States and the 250 pg/m* 24-hour average for the United Kingdom. Measurements of environmental smoke concentrations vary wide- ly, depending upon the location and measurement technique (Tables 4 and 5). Levels of total suspended particulates (TSP) measured under realistic circumstances have been found to be from 20 to 60 ug/m* in no-smoking areas, and can range from 100 to 700 pe/m’ in the presence of smokers (Repace and Lowrey 1980). These measure- ments include all suspended particulates, and so could include particles other than tobacco smoke. However, in a smoky indoor setting where measurements as high as 600 ug/m* have been found, tobacco smoke is the major contributor to particulate mass, with the non-tobacco-smoke contribution being small and similar to that measured for nonsmoking areas, namely in the 20 to 60 pg/m* range. This concept is supported by studies in which tobacco smoke concentration in the environment was determined by measuring the nicotine content of suspended particulates. Using this technique (Hinds and First 1975), ETS levels have been estimated to be 20 to 480 pg/m* in bus and airline waiting rooms and as high as 640 pg/m? in cocktail lounges. These calculations of smoke concentrations were based on an average weighted nicotine fraction of 2.6 percent, an approach that may underestimate tobacco smoke particulate concen- tration. The mass deposition in the respiratory tract can be estimated if the atmospheric burden of cigarette smoke particulates, minute volume, and deposition fraction is known. Assuming a smoke concentration of 500 g/m, a minute volume of 12 liters per minute, 193 FET TABLE 4.—Indoor concentration of total suspended particulates (TSP) measured in ordinary living or working situations Conditions of location, TSP Background occupancy, smoking (§), -—_— ee Study Location nonsmoking (NS) pm/m’ x +SD pm/m* Comments Just et al. Coffee shop 4 locations 1,150 570! (1972) Hinds and First Bus waiting 40 Not applicable Suspended particulates (1975) room (16-68) collected on filter; nicotine Restaurant Not given 200 content measured for (51-450) calculation; TSP = Cocktail Not given 400 nicotine/0.026 lounge (170-640) Elliott and Rowe Arena A Attendance 9,600 224 42 High volume sampler for (1975) Air conditioned (8) suspended particulates; also Attendance 14,300 481 42 measured CO at all locations Air conditioned (S) and benzofa}pyrene in arena A Arena B Attendance 2,000 620 92 Not air conditioned (5S) Arena C Attendance 11,000 148 71 Natural ventilation (NS) Cuddeback et al. Tavern 6 air changes/hr 0.31 + 0.05 Shr air sample collected on (1976) (0.23-0.34) filter (56 um pore size); TSP Tavern None apparent 0.99 measured gravimetrically Neal et al. Hospital Independent ventilation 30 68 Anderson personnel sampler (1978) intensive systems used care units c6T TABLE 4.—Continued Conditions of location, TSP Background occupancy, smoking (S), __ Study Location nonsmoking (NS) pm/m* x +SD jum/m* Comments Weber and Fischer 44 offices Window ventilation; 202 Subtracted from TSP measured with (1980) 32/44 allowed unrestricted TSP piezoelectric balance (see smoking above) Air conditioned 120 Same Repace and Lowrey Residences 5 locations, 6 measurements: 38 + 16 Not done All samples collected using (1980) 10 + 8 persons/100 m’, all piezoelectric balance with very NS high collection efficiency at 3.5 Libraries, 9 locations; 10 + 10 38 + 16 36 + 10' um and 10% at 4 4m; sample churches, persons/100 m°, all NS (4 locations) time 1-50 min, outdoors 5-15 restaurants min Restaurants, 19 locations, 20 samples, 11 242 + 176 47 + 13) bars, bingo + 8 persons/100 m*, all S (86-697) (13 locations) game locations 7 locations with >1 406 + 188 53 + 8) smoker/m* (mean 2.2 smokers/m‘) (187-697) 18 + 7 persons/100 m*, with 1 smoker/100 m* 96T TABLE 4.—Continued Conditions of location, TSP Background occupancy, smoking (S), o_O Study Location nonsmoking (NS) pm/m® x +SD pm/m* Comments Spengler et al. 35 homes No smokers 24.4 + 11.6' 21.1 + 119 Annual mean: respirable mass (1981) 15 homes 1 smoker 36.5 + 14.5 all 55 homes collected on filters after 5 homes 2 smokers 70.4 + 42.9 removal of nonrespirable fraction; 24-hr sample collected every 6 days 1 home* 2 smokers, tightly sealed, 144 central air conditioning : Ambient particulate concentration at site, but outdoors. ® This home is one of the five homes above. L6T TABLE 5.—Indoor concentration of total suspended particulates (TPM) generated by smoking cigarettes under laboratory conditions Chamber Cigarette TPM Study Test conditions Ventilation size consumption mg/m? Comments Penkala and Well mixed None 9.2 m? 3 simultaneously, 2 q 38 de Oliveira (1975) puffs Hoegg Sealed chamber; Portable fans 25 m? 24 simultaneously by 16.65 TPM measured gravimetrically (1972) experimenter and test circulated air machine after collection of suspended equipment in chamber, particulates on filters; measured 18 min sidestream smoke collected in postsmoking chamber; mainstream smoke discharged Same, 150 min Same 4 simultaneously by 151 postsmoking machine Hugod et al. Sealed room Unventilated 68 m* 20 simultaneously by 5.75 TPM measured gravimetrically (1978) machine from Shr collection on filter; mainstream smoke in chamber Cain et al. 4-12 occupants 11 ft*/min/ocecupant 11 m? 4/hr (by occupants) 0.350 Piezoelectric balance measured (1983) Climate-controlled 68 ft?/min/occupant 11 m‘ 4/hr (by occupants) 0.15 total mass over 0.01-20 um chamber 11 ft*/min/occupant 11 m* 16/hr (by occupants) 1.26 68 ft?/min/occupant 11 m' 16/hr (by occupants) 0.40 Muramatsu Climate-controlled 16.4 air changes/hr 30 m* 1/8 min to 60 min 0,19-0.26 Piezoelectric balance et al. (1983) chamber Climate-controlled 16.4 air changes/hr 30 m?® 3 simultaneoualy, then 0.47-0.522 chamber 2/8 min and a deposition fraction of 11 percent (Hiller, McCusker et al. 1982), mass deposition over an 8-hour work shift would be 0.317 mg. The Concept of “Cigarette Equivalents” Many investigators have attempted to estimate the potential toxicity of involuntary smoking for the nonsmoker by calculating “cigarette equivalents” (C.E.). To inhale one C.E. by involuntary smoking, the involuntary smoker would inhale the same mass quantity of ETS as is inhaled from one cigarette by a mainstream smoker. This approach has led to estimates from as low as 0.001 C.E. per hour to as high as 27 C.E. per day (Hoegg 1972; Hinds and First 1975; Hugod et al. 1978; Repace and Lowrey 1980). These differences of up to three orders of magnitude seem illogical when most reports of measurements of environmental concentrations of smoke, from the most clean to the most polluted with environmental tobacco smoke, are within tenfold to fiftyfold of each other. The following discussion demonstrates why the C.E. can vary so greatly as a measure of exposure. The calculation of CE. is as follows: PMI.) = TSP (mg/m*) x Vz; where PMIip equals the particulate mass inhaled by passive smoking, TSP equals the total suspended particulate, and Ve equals the inhaled volume. C.E. = PMIp/PMIms; where C.E. equals cigarette equivalent and PMIim) equals the mass inhaled by (mainstream) smoking one cigarette. (This is taken to be the tar content of a cigarette as reported by the U.S. Federal Trade Commission.) Cigarette equivalents can be calculated for any time interval chosen, i.e., per hour, per day. Although the example given is for particulate mass, C.E. can be calculated for any component of cigarette smoke, such as carbon monoxide and benzo[a]pyrene. The following calculations illustrate the different results from two different approaches to the calculation of C.E. Example 1 Example 2 Ve 0.36 m?/hr 20 m®/day PMIins) 16.1 mg tar/cig 0.55 mg tar/cig TSP 40 pg/m* 700 pg/m?® Example 1 PMI,» = TSP x Vz = 40 pein x 0.36 m*/hr = 14.4 pg/hr C.E. = PMIp/PMIus = (0.0144 mg/hr)/(16.1 mg/cig) = 0.001 cig/hr 198 Example 2 PMI) ASP x Ve, g/m? x 20 m*/da: 14,000 pe/day y Gg re 710.55 mg/day)/(0. fei 25 cig/day mer eig) These calculations of CE. approximate the approaches used in two ports—Example 1 by Hinds and First (1975) and Example 2 by Repace and Lowrey (1980)—and the results are similar. The exam- ples are the extremes used in the two studies, and are at the extremes of commonly cited reports of C.E. Even if the TSP etl CE. Hel i Example 2 is calculated per day; 2.3-fold because of the difference in inhaled minute volume; and 29-fold because of the difference in what is considered to be a “standard” cigarette. Even using the same TSP concentration, the results would be 1.6 x 10° different, If C.E. is to be calculated, all of the factors used in the calculation should be The differences in the chemical composition between sidestream smoke and mainstream smoke make the C.E. concept misleading fivefold rise in TSP above background and an eighteenfold increase in benzo[a]pyrene over background. Using the measured ben- zo{a]pyrene concentration of 21.7 ng/m*, an inhaled volume of 2.4 m*, and 8.2 ng benzo[a]pyrene per cigarette, the occupant of such an environment would consume 6.4 C.E. for benzo[a]pyrene (IARC 1986, p. 87). The CE. TSP would be 1.7. Therefore, a C.E. for the 199 carcinogen benzofalpyrene would be inhaled 3.6 times more rapidly than a C.E. for TSP (Elliott and Rowe 1975). . The wide latitude in the results of C.E. calculations demonstrates the dependence of the C.E. calculation on the numerical values of the variables chosen, and correspondingly demonstrates the marked limitations of the use of C.E. as an atmospheric measure of exposure to the agents in environmental tobacco smoke. When the quantifica- tion of an exposure is needed, it is far more precise to use terms that define the milligrams of exposure to the agent of interest per unit time. However, the term cigarette equivalent is frequently used, not simply as a measure of exposure, but as a unit of disease risk that translates the measured exposures into a risk of disease using the known dose-response relationships between the number of ciga- rettes smoked per day and the risk of disease. If C.E. is to be used as a unit of risk, the variables used to convert atmospheric measures into levels of risk for the active smoker need to be determined on the basis of the deposition and smoke exposure measures for the average smoker. The deposition fraction of individual smoke constituents in the population of active smokers is needed rather than the range observed in a few individuals. In addition, the actual average yield of the cigarettes smoked by the subjects in the prospective mortality studies would be needed to compare the dose-response relationships accurately. The yield using the Federal Trade Commission (FTC) method may dramatically underestimate the actual yield of a cigarette when the puff volume, rate of draw, or number of puffs is increased; therefore, calculations using the FTC numbers may be inaccurate, particularly for the low-yield cigarettes. These limita- tions make extrapolation from atmospheric measures to cigarette equivalent units of disease risk a complex and potentially meanin- gless process. Markers of Absorption In contrast, measures of absorption of environmental tobacco smoke, particularly cotinine levels, can potentially overcome some of the limitations in translating environmental tobacco smoke expo- sures into expected disease risk. Urinary cotinine levels are a relatively accurate dosage measure of exposure to smoke; they have been measured in populations of smokers and nonsmokers, and are not subject to errors in estimates of the minute ventilation or yield of the average cigarette. Potential differences in the half-life of cotinine in smokers and nonsmokers, differences in the absorption of nicotine relative to other toxic agents in the smoke, and differences in the ratio of nicotine to other toxic agents in mainstream smoke and sidestream smoke remain sources of error, but the accuracy with which active smoking and involuntary smoking exposure can be 200 compared is almost certainly substantially greater with measures of absorption than with atmospheric measures. Tobacco smoke contains many substances, but only a few have been measured in human biological fluids. Of the gaseous compo- nents, markers include carbon monoxide and thiocyanate. The latter is not a gas but a metabolite of gaseous hydrogen cyanide. Concentra- tions of nicotine and its metabolite cotinine are markers of nicotine uptake. In mainstream smoke, nicotine uptake reflects exposure to particulates. In environmental tobacco smoke, nicotine becomes vaporized and therefore reflects gas phase exposure (Eudy et al. 1985). Quantitating tar consumption is more difficult; urinary mutagenic activity has been used as an indirect marker. The relative exposures of nonsmokers to various tobacco smoke constituents differs from that of smokers. Assuming that exposure to a single tobacco smoke constituent accurately quantifies the expo- sure of both smokers and nonsmokers to other constituents is inaccurate because mainstream smoke and environmental tobacco smoke differ in composition (see Chapter 3). To understand the usefulness and limitations of various biochemi- cal markers, it is important to appreciate the factors that influence their absorption by the body and their disposition kinetics within it. Carbon Monoxide Carbon monoxide is absorbed in the lungs, where it diffuses across the alveolar membrane (Lawther 1975; Stewart 1975). It is not appreciably absorbed across mucous membranes or bronchioles. Within the body, carbon monoxide binds, as does oxygen, to hemoglobin, where it can be measured as carboxyhemoglobin. Carbon monoxide may also be bound to myoglobin and to the cytochrome enzyme system, although quantitative details of binding to the latter sites are not available. Carbon monoxide is eliminated primarily by respiration. The amount of ventilation influences the rate of elimination. Thus, the half-life of carbon monoxide during exercise may be less than 1 hour, whereas during sleep it may be greater than 8 hours (Castleden and Cole 1974). At rest, the half-life is 3 to 4 hours. The disposition kinetics of carbon monoxide explain the temporal variation of carbon monoxide concentration in active smokers during a day of regular smoking. With a half-life averaging 3 hours and a reasonably constant dosing (that is, a regular smoking rate), carbon monoxide levels will plateau after 9 to 12 hours of cigarette smoking. This has been observed in studies of circadian variation of carbon monoxide concentrations in cigarette smokers (Benowitz, Kuyt et al. 1982). Smoking is not a constant exposure source, but results in pulsed dosing. There is a small increment in carboxyhemoglobin level immediately after smoking a single cigarette, which then 201 declines until the next cigarette is smoked. But after several hours of smoking, the magnitude of rise and fall is small compared with the trough values. For this reason, carboxyhemoglobin levels at the end of a day of smoking are satisfactory indicators of carbon monoxide i t day. See oor mecide cxposure may be more ‘constant during environ- mental tobacco smoke exposure than during active smoking. The major limitation in using carbon monoxide as a means of measuring involuntary smoke exposure is its lack of specificity. Endogenous carbon monoxide generation from the metabolism of hemoglobin results in a low level of carboxyhemoglobin (up to 1 percent) (Lawther 1975; Stewart 1975). Carbon monoxide is generated by any source of combustion, including gas stoves, machinery, and automo- bile exhaust. Thus, nonsmokers in a community with moderate home and industrial carbon monoxide sources may have carboxyhemoglo- bin levels of 2 or 3 percent (Woebkenberg et al. 1981). A carbon monoxide level of 10 in room air results in an increment of 0.4 and 1.4 percent carboxyhemoglobin at 1 and 8 hours of exposure time, respectively (Lawther 1975; Stewart 1975). Thus, small increments of carbon monoxide due to environmental tobacco smoke may be indistinguishable from that due to endogenous and non-tobacco- related sources. Measurement of carbon monoxide is straightforward and inexpen- sive. Alveolar carbon monoxide pressures are proportional to the concentration of carboxyhemoglobin in blood; therefore, end-tidal carbon monoxide tension accurately reflects blood carboxyhemoglo- bin (Jarvis and Russel] 1980). Expired carbon monoxide can be measured using an instrument (Ecolyzer) that measures the rate of conversion of carbon monoxide to carbon dioxide as it passes over a catalytically active electrode. Blood carboxyhemoglobin can be measured directly and quickly using a differential spectrophotome- ter. Thiocyanate Hydrogen cyanide is metabolized by the liver to thiocyanate. In addition to tobacco smoke, certain foods, particularly leafy vegeta- bles and some nuts, are sources of cyanide. Cyanide is also present in beer. Thiocyanate is distributed in extracellular fluid and is eliminated slowly by the kidneys. The half-life of thiocyanate is long, about 7 to 14 days. Thiocyanate is also secreted into saliva, with salivary levels about 10 times that of plasma levels (Haley et al. 1983). The long half-life of thiocyanate means that there is little fluctuation in plasma thiocyanate concentrations during a day or from day to day. Thus, the time of sampling is not critical. On the other hand, a given level of thiocyanate reflects exposure to hydrogen cyanide over 202 several weeks Preceding the time of sampling. When a smoker stops smoking, it takes an estimated 3 to 6 weeks for thiocyanate levels to reach that individual’s nonsmoking level. nonsmokers (Vogt et al. 1979: Jacob et al. 1981), light smokers or involuntary smokers may have little or no elevation of thiocyanate. When thousands of subjects are studied, involuntary smokers have been found to have slightly higher thiocyanate levels than those without exposure (Friedman et al. 1983). Other studies of smaller numbers of subjects have shown no difference in thiocyanate level between exposed or nonexposed nonsmokers (Jarvis et al. 1984). Serum or plasma thiocyanate levels can be measured using spectrophotometric methods or, alternatively, gas chromatography. Nicotine Nicotine is absorbed through the mucous membranes of the mouth and bronchial tree as well as across the alveolar capillary mem- brane. The extent of mucosal absorption varies with the PH of the smoke, such that nicotine is absorbed in the mouth from alkaline (cigar) smoke or buffered chewing gum, but very little is absorbed from acidic (cigarette) mainstream smoke (Armitage and Turner 1970). With aging, environmental tobacco smoke becomes less acidic; pH may rise to 7.5, and buccal or nasal absorption of nicotine by the nonsmoker could occur (see Chapter 3). Nicotine is distributed rapidly to body tissues and is rapidly and extensively metabolized by the liver. Urinary excretion of unmetabo- lized nicotine is responsible for from 2 to 25 percent of total nicotine elimination in alkaline and acid urine, respectively; nicotine excre- tion also varies with urine flow (Rosenberg et al. 1980). Exposure to environmental tobacco smoke, active smoking, and use of smokeless tobacco markedly elevate salivary nicotine transiently out of propor- tion to serum and urinary levels (Hoffmann et al. 1984). Nicotine is present in breast milk (Luck and Nau 1985), and the concentration in the milk is almost three times the serum concentration in the mother (Luck and Nau 1984). The rate of nicotine metabolism varies considerably, as much as fourfold among smokers (Benowitz, Jacob et al. 1982). There is evidence that nicotine is metabolized less rapidly by nonsmokers than by smokers (Kyerematen et al. 1982). A given level of nicotine in the body reflects the balance between nicotine absorption and the metabolism and excretion rates. Thus, in comparing two persons with the same average blood concentration of nicotine, a rapid metabolizer may be absorbing up to four times as much nicotine as a slow metabolizer. To determine daily uptake of nicotine directly, 203 both the nicotine blood concentrations and the rates of metabolism and excretion must be known. These variables can be measured in experimental studies (Benowitz and Jacob 1984; Feyerabend et al. 1985), but are not feasible for large-scale epidemiologic studies. The time course of the decline of blood concentrations of nicotine is multiexponential. Following the smoking of a single cigarette or an intravenous injection of nicotine, blood concentrations of nicotine decline rapidly owing to tissue uptake, with a half-life of 5 to 10 minutes. If concentrations are followed over a longer period of time or if multiple doses are consumed so that the tissues are saturated, a longer elimination half-life of about 2 hours becomes apparent (Benowitz, Jacob et al. 1982; Feyerabend et al. 1985). Because of the rapid and extensive distribution in the tissues, there is considerable fluctuation in nicotine levels in cigarette smokers during and after smoking. As predicted by the 2-hour half-life, nicotine blood concen- trations increase progressively and plateau after 6 to 8 hours of regular smoking (Benowitz, Kuyt et al. 1982). Nicotine concentra- tions have been sampled in the afternoon in studies of nicotine uptake during active cigarette smoking (Benowitz and Jacob 1984), and similar timing might be appropriate in assessing the plateau levels that result from continuous ETS exposure, such as during a workday. - Russell and colleagues (1985) quantitated nicotine exposure by comparing blood nicotine concentrations during intravenous infu- sions (0.5 to 1.0 mg over 60 minutes) in nonsmokers to the blood nicotine concentrations in nonsmokers exposed to environmental tobacco smoke. The data suggest that nicotine uptake in a smoky bar in 2 hours averaged 0:20 mg per hour. _ The presence of nicotine in biologic fluids is highly specific for. tobacco or tobacco smoke exposure. Nicotine concentration is sensi- tive to recent exposure because of nicotine’s relatively rapid and extensive tissue distribution and its rapid metabolism. Urinary nicotine concentration has been examined in a number of studies of environmental tobacco smoke exposure. Although influenced by urine pH and flow rate, the excretion rate of nicotine in the urine reflects the concentration of nicotine in the blood over the time period of urine sampling. In other words, nicotine excretion in a timed urine collection is an integrated measure of the body’s exposure to nicotine during that time. When timed urine collections are not available, nicotine excretion is commonly expressed as a ratio of urinary nicotine to urinary creatinine, which is excreted at a relatively constant rate throughout the day. Urinary nicotine excretion is highly sensitive to environmental tobacco smoke expo- -sure (Hoffmann et al. 1984; Russell and Feyerabend 1975). Saliva levels of nicotine rise rapidly during exposure to sidestream smoke and fall rapidly after exposure has ended (Hoffmann et al. 1984). 204 Presumably, this time course reflects local mouth contamination, followed by absorption or the swallowing of nicotine. Blood, urine, or saliva concentrations of nicotine can be measured by gas chromatography, radioimmunoassay, or high pressure liquid chromatography. Sample preparation is problematic in that contam- ination of samples with even small amounts of tobacco smoke can substantially elevate the normally low concentrations of nicotine in the blood. Thus, careful precautions against contamination during sample collection and processing for analysis are essential. Because the concentrations are so low, the measurement of nicotine in blood has been difficult for many laboratories in the past, but with currently available assays, it is feasible for large-scale epidemiologic studies. Cotinine Cotinine, the major metabolite of nicotine, is distributed to body tissues to a much lesser extent than nicotine. Cotinine ig eliminated primarily by metabolism, with 15 to 20 percent excreted unchanged in the urine (Benowitz et al. 1983). Urinary pH does affect the renal elimination of cotinine, but the effect is not as great as for nicotine. Since renal clearance of cotinine is much less variable than that of nicotine, urinary cotinine levels reflect blood cotinine levels better than urinary nicotine levels reflect blood nicotine levels. Plasma, urine, and saliva cotinine concentrations correlate strongly with one another (Haley et al. 1983; Jarvis et al. 1984). The elimination half-life for cotinine averages 20 hours (range, 10 to 37 hours) (Benowitz et al. 1983). Because of the relatively long half-life of cotinine, blood concentrations are relatively stable throughout the day for the active smoker, reaching a maximum near the end of the day. Because each cigarette adds relatively little to the overall cotinine level, sampling time with respect to smoking is not critical. Assuming that smoke exposure occurs throughout the day, a midafternoon or late afternoon level reflects the average cotinine concentration. The specificity of cotinine as a marker for cigarette smoking is excellent. Because of its long ‘half-life and its high specificity, cotinine measurements have become the most widely accepted method for assessing the uptake of nicotine from tobacco, for both active and involuntary smoking. Cotinine levels can be used to generate quantitative estimates of nicotine absorption. Galeazzi and colleagues (1985) defined a linear relationship between nicotine uptake and plasma cotinine levels in six healthy volunteers who received several i.v. doses of nicotine (< 480 pg/kg/day) for 4 days. The ability to extrapolate from this model to levels in nonsmokers is limited, however, because the elimination half-life of cotinine may be shorter in smokers than in 205 nsmokers, as is the elimination half-life of nicotine (Kyerematen ial. 1982). Cotinine can be assayed by radioimmunoassay, gas chromatogra- phy, and high pressure liquid chromatography. Urinary Mutagenicity Tobacco smoke condensate is strongly mutagenic in bacterial test systems (Ames test) (Kier et al. 1974). A number of compounds, including polycyclic aromatic hydrocarbons, contribute to this mutagenicity. The urine of cigarette smokers has been found to be mutagenic, and the number of bacterial revertants per test plate is related to the number of cigarettes smoked per day (Yamasaki and Ames 1977). Urinary mutagenicity disappears within 24 hours after smoking the last cigarette (Kado et al. 1985). For several reasons, the measurement of mutagenic activity of the urine is not a good quantitative measure of tar absorption. Individu- als metabolize polycyclic aromatic hydrocarbons and other mutagen- ic substances differently. Only a small percentage of what is absorbed is excreted in the urine as mutagenic chemicals. The bacterial system is differentially sensitive to different mutagenic compounds. The urine of smokers presumably contains a mixture of many mutagenic compounds. In addition, the test lacks specificity, in that other environmental exposures result in urinary mutagenicity. The test may also be insensitive to very low exposures such as involuntary smoking. However, one study, by Bos and colleagues (1983), indicated slightly increased mutagenic activity in the urine of nonsmokers following tobacco smoke exposure. The presence of benzo[a]pyrene and 4-amino biphenyl covalently bound to DNA and hemoglobin in smokers (Tannenbaum et al., in press) suggests other potential measures of carcinogenic exposure. Whether such measures will be sensitive to ETS exposure is unknown. The development of specific chemical assays for human exposure to components of cigarette tar remains an important research goal. Populations In Which Exposure Has Been Demonstrated Absorption of tobacco smoke components by nonsmokers has been demonstrated in experimental and natural exposure conditions. Experimental Studies Nonsmokers have been studied after exposures in tobacco-smoke- filled rooms. The smoke may be generated by a cigarette smoking machine or by active smokers placed in the room by the investigator, or the location may be a predictably smoke-filled environment such as a bar. The level of environmental smoke has most often been 206 quantitated by measuring ambient carbon monoxide concentrations. In nonsmokers exposed for 1 hour in a test room with a carbon a public house (bar) with a carbon monoxide level of 13 ppm; their expired carbon monoxide increased twofold and their urinary nicotine excretion increased ninefold (Jarvis et al. 1983). In a study exposing eight nonsmokers to a smoke-filled room for 6 hours, a small increase in urinary mutagenic activity was measured (Bos et al. 19838). Nonexperimental Exposures Exposure studies performed in real-life situations have compared biochemical markers of tobacco smoke exposure in different individ- uals with different self-reported exposures to tobacco smoke. Absorp- tion of nicotine (indicated by urinary cotinine levels) was found to be increased in adult nonsmokers if the Spouse was a smoker (Wald and Ritchie 1984). In another study (Matsukura et al. 1984), urinary cotinine levels in nonsmokers were increased in proportion to the presence of smokers and the number of cigarettes smoked at home and the presence and number of smokers at work. Blood and urinary nicotine levels were increased after occupational exposure to ETS such as a transoceanic flight by commercial airline flight attendants (Foliart et al. 1983). Nicotine absorption, documented by increased salivary cotinine concentration, has been shown in schoolchildren in relationship to the smoking habits of the parents (Jarvis et al. 1985), and using plasma, urinary, and saliva measures, in infants in relation to the smoking habits of the mother (Greenberg et al. 1984; Luck and Nau 1985; Pattishall et al. 1985). Quantification of Absorption Evidence of Absorption in Different Populations One questionnaire survey indicated that 63 percent of individuals report exposure to some tobacco smoke (Friedman et al. 1983), Thirty-four percent were exposed for 10 hours and 16 percent for 40 or more hours per week. The distribution of cotinine levels in a few populations has been reported. In men attending a medical screening examination, there was a tenfold difference in mean urinary cotinine in nonsmokers with heavy exposure (20 to 80 hours per week) compared with those who reported no ETS exposure (Wald et al, 1984). The median and 90th percentile urinary cotinine concen- trations for all nonsmokers who reported exposure to other people’s smoke were 6.0 and 22.0 ng/mL, respectively, compared with a median of 1645 ng/mL for active smokers. In 569 nonsmoking 207 schoolchildren, salivary cotinine concentrations were widely distrib- uted. Values were strongly influenced by parental smoking habits (Jarvis et al. 1985). The median and 25 to 75 percent ranges (in ng/mL) were 0.20 (0-0.5), 1.0 (0.4-1.8), 1.35 (0.7-2.7), and 2.7 (1.5-4.4) for children whose parents did not smoke or whose father only, mother only, or both parents smoked, respectively. Quantification of Exposure Expired carbon monoxide, carboxyhemoglobin, plasma thiocya- nate, plasma or urinary nicotine, and plasma, urinary, or salivary cotinine have been used to evaluate exposure to ETS. However, successful attempts to quantify the degree of exposure have been limited largely to measurements of nicotine and cotinine. Expired carbon monoxide and carboxyhemoglobin have been found to be increased up to twofold after experimental or natural exposures (Russell et al. 1973), but not in more casually exposed subjects. Thiocyanate was slightly increased in one very large study of heavily exposed individuals (Friedman et al. 1983), but most studies report no differences as a function of involuntary smoking exposure. The most useful measures appear to be nicotine and cotinine. The data on nicotine and cotinine measurements are presented in Tables 6 and 7 and suggest the following: (1) Both nicotine and cotinine are sensitive measures of environ- mental tobacco smoke exposure. Levels in body fluids may be elevated 10 or more times in the most heavily exposed groups compared with the least exposed groups. (2) The time course of change in the levels of biochemical markers depends on which marker is selected and which fluid is sampled. There is a lag between peak blood levels of nicotine and peak blood levels of cotinine, owing to the time required for metabolism (Hoffmann et al. 1984). Salivary levels of nicotine, because of the local deposition of smoke in the nose and mouth, peak early and decline rapidly. (3) With nicotine, salivary levels increase considerably after environmental tobacco smoke exposure, but decline rapidly follow- ing the end of exposure. Blood nicotine levels are too low to be very useful in quantitating environmental nicotine exposure. Urinary nicotine is a sensitive indicator of passive smoke exposure, but because of its relatively short half-life, urinary nicotine levels decline within several hours of the time of exposure. (4) Cotinine levels are less susceptible than nicotine to transient fluctuations in smoke exposure. Blood or plasma, urine, and saliva concentrations correlate strongly with one another. Because of the stability of cotinine levels measured at different times during an exposure and the availability of noninvasive (ie., urine or saliva) 208 TABLE 6.—Nicotine measures in nonsmokers with environmental tobacco smoke (ETS) exposure and comparisons with active smoking Mean or median concentration and range Plasma nicotine Urine nicotine Saliva nicotine (ng/mL) (ng/mL) (ng/mL) Number of Smoking Study subjects status Exposure level Before After Before After Before After Russell and 12 NS 78 min in 0.78 0.90 _ 80 (13-208) _ _ Feyerabend smoke-filled room (1975) 14 NS Hospital _ - - 12.4 (0.8-64.3) _ _- 18 NS employees - _ 8.9 (0-26) _ - 18 8 Average 24 cigs/day - =- - 1236 (104-2733) - - Feyerabend 26 NS No S exposure _ - - 15 _ 59 et al. (1982) 30 NS Work exposure ~ - - 21.6 _ 10.1 8 S- Noninhalers — _ _ 387 - 182 15 5 Slight inhalers ~ _ ~ 1261 — 421 32 s Medium inhalers _ _ _ 1349 ~ 454 a S Deep inhalers — - — = -:1827 ~ 905 Foliart et al. 6 NS Flight attendants 16 32 — 15.2 (83-344) - = (1983) (0.8-2.7) (1.6-4.5) Jarvis et al. 7 NS Before, 11:30 a.m. 08 2.5 105° 926 19 43.6 (1983) After, public house x 2hr Hoff t al. 10 NS Experimental chamber (98) ° 2 cigs burned 11 11 2a! 51? 8 427 3 cigs burned ND 13 20 4 1 893 0.2 0.5 17 100 3 790 4 cigs burned 01% TABLE 6.—Continued Mean or median concentration and range Plasma nicotine Urine nicotine Saliva nicotine (ng/mL) (ng/mL) (ng/mL) Number of Smoking Study subjects status Exposure level Before After Before After Before After Jarvis et al. Hospital clinic patients (1984) 46 NS No exposure =- 10 - 3.9 _ 3.8 2 NS Little exposure _ 0.8 ~ 122 _ 48 20 NS Some exposure — 07 _ 11.9 ~~ 44 7 NS Lot of exposure _— 0.9 - 12.2 - 12.1 94 s _ 14.8 _ 1750 _ 672 Greenberg 82 NS Infants, mother S _— _- _— §3' (0-370) _ 12.7 (0-166) et al. (1984) 19 NS Infant, mother NS - - — 0 (0-59) - 0 (0-17) Luck and Nau 10 NS, neonates §_No exposure = _ _ 0! @-14) _ _ (1985) 10 NS, neonates Nursed by § mother; _- - _ 14 (6-110) - _ no ETS exposure 10 NS, infants S mother, not nursed - _ - 35 (4-218) - - 9 NS, infants Nursed by 5 mother; _- - - 12 (3-42) - - 1 ng/mg creatinine. ETS exposure TTS TABLE 7.—Cotinine measures in nonsmokers with environmental smoke exposure and comparisons with active smoking Mean or median concentration and range Plasma ‘cotinine Urine cotinine Saliva cotinine Number (ng/mL) (ng/mL) (ng/mL) of Smoking Study subjects status Exposure level Before After Before After Before After Jarvis 7 NS Before, 11:30 a.m. 11 13 48 12.9 15 8.0 et al. After, public house x 2 hr (1983) Jarvis Hospital clinic patients et al. 46 NS No exposure _ 08 _ 16 _ 0.7 (1984) 27 NS Little exposure oo 18 - 65 -_ 22 20 NS Some exposure _ 2.5 _ 86 _ 28 7 NS Lot of exposure - 18 _ 9.4 > 26 94 8s -_ 276 _ 1391 _ 310 Hoffmann 10 NS Experimental chamber et al. 2 cigs burned 17 2.6 (peak 14 21 12 23 (1984) 3 cigs burned 1.0 3.0 change) 14 88 17 25 4 cigs burned 0.9 3.3 14 55 1.0 14 Wald and = 101 NS Wife abstinent - _ 8.5 (median 5.0) Ritchie 20 NS Wife smoker _ _- 25.2 (median 9.0) (1984) o1S TABLE 7.—Continued Mean or median concentration and range Plasma cotinine Urine cotinine Saliva cotinine Number (ng/mL) (ng/mL) (ng/mL) of Smoking Study subjects status Exposure level Before After Before After Before After Wald Med screening clinic patients et al. 221 NS Research colleagues - 112 (1984) 43 NS 0-1.5 br ETS exposure/wk — 2.8 47 NS 1.5-4.5 hr ETS exposure/wk — 3.4 48 NS 4.5-86 hr ETS exposure/wk -_ 53 43 NS 8.6-20 hr ETS exposure/wk —_ 14.7 45 NS 20-80 hr ETS exposure/wk - 29.6 131 s Cigarettes — 1645 (587-3326) 59 s Cigars _ $96 (61-2138) 42 S Pipes _ 1920 (1008-4569) Matsukura 200 NS No home exposure - 510! et al. 272 NS All home exposure - 790 (1984) Home exposure: 25 NS 1-9 cig/day - 310 57 NS 10-19 cig/day - 420 99 NS 20-29 cig/day -_ 870 38 NS 30-39 cig/day - 1030 28 NS > 40 cig/day - 1560 472 NS All _ 680 302 s All - 8520 16 NS No workplace exposure - 220 21 NS Workplace exposure _ 7120 €12 TABLE 7.—Continued Mean or median concentration and range Numbe Plasma cotinine Urine cotinine Saliva cotinine umber (ng/mL) (ng/mL) of Smoking “ (o¢/mL) Study subjects status Exposure level Before After Before After Before After Greenberg 32 NS, infants S mother _ 351 (41-1888) _ 9 (0-25) et al. 19 NS mother - 4 (0-125 _— (1984) ( ) 0 @-3) Jarvis Children aged 11-16 et al, 269 NS Neither parent SM _ 04 (1985) (median 0.2) 96 NS SM father - 13 (1.0) 76 NS SM mother _ 2.0 (1.7) 128 NS Both parents SM — 3.4 (2.4) Luck and 10 NS, neonates No exposure - —_ _ 0' (0-56) ~ _ Nau 19 NS, neonates Nursed by S mother: - _ - 100 (10-555) _ _ (1986) no ETS exposure 10 NS, infants 5 mother, not nursed _ — _ 827 (117-780) _ - 9 NS, infants S mother, nursed; - _ _ 550 (225-870) _- - ETS exposure Serum cotinine (ng/mL) Pattishall 20 NS, children Smokers in home _ 41 ~ - — _ et al. 18 NS, children No amokers in home — 10 ~ ~~ _ a (1985) bIS TABLE 7.—Continued Mean or median concentration and range Plasma cotinine Urine cotinine Saliva cotinine Number (ng/mL) . (ng/mL) (ng/mL) of Smoking Study subjects status Exposure level Before After Before After Before After Coultas 68 NS aged <5 No amokers in home - — - _ — 0, 1.77 et al. 41 NS aged <5 — 1 smoker in home _ _ = _ - 3.8, 4.1 (1986) 21 NS aged <5 2 or more smokers in home - _ =- _ — 5.4, 5.6 200 NS aged 6-17. No amokers in home _ _ - _ ~ 0, 1.3 96 NS aged 6-17 1 smoker in home — _ - _ - 1.8, 2.4 25 NS aged 6-17 2 or more smokers in home - _ _ _- _ 5.3, 5.6 316 NS aged >17 No smokers in home _ — = — — 0, 15 60 NS aged >17 1 smoker in home _ - . — - — 0.6, 2.8 12 NS aged >17 2 or more smokers in home — _ — _ _ 0, 3.7 ‘ ng/mg creatinine. * median, mean. measurements, cotinine appears to be the short-term marker of choice for epidemiological studies. (5) Mean levels of urinary nicotine and of cotinine in body fluids increase with an increasing self-reported ETS exposure and with an Comparison of Absorption From Environmental Tobacco Smoke and From Active Smoking Epidemiologic studies show a dose-response relationship between number of cigarettes smoked and lung cancer, coronary artery disease, and other smoking-related diseases. Assuming that dose- response relationships hold at the lower dose end of the exposure— response curve, risks for nonsmokers can be estimated by using measures of absorption of tobacco smoke constituents to compare the relative exposures of active smokers and involuntary smokers, As discussed previously, measures of nicotine uptake (Le., nicotine or cotinine) are the most specific markers for ETS exposure and provide the best quantitative estimates of the dose of exposure. Although the ratio of nicotine to other tobacco smoke constituents differs in mainstream smoke and sidestream smoke, nicotine uptake may still be a valid marker of total ETS exposure. Nic¢sjne uptake in nonsmokers can be estimated in several ways. Russell and colleagues (1985) infused nicotine intravenously to nonsmokers and compared resultant plasma and urine nicotine levels with those observed in nonsmokers with ETS exposure. An infusion of 1 mg nicotine over 60 minutes resulted in an average plasma nicotine concentration of 6.6 ng/mL and an average urinary nicotine concentration of 224 ng/mL. Using these data in combina- tion with measured plasma and urinary nicotine levels in nonsmok- ers after 2 hours in a smoky bar, nicotine uptake was estimated as 0.22 mg per hour. Since the average nicotine uptake per cigarette is 1.0 mg (Benowitz and Jacob 1984; Feyerabend et al. 1985), 0.22 mg of nicotine is equivalent to smoking about one-fifth of a cigarette per hour. In making these calculations, it is assumed that the disposition kinetics of inhaled and intravenous nicotine are similar and that the rate of nicotine exposure from ETS is constant. Steady state blood cotinine concentrations can also be used to estimate nicotine uptake. Galeazzi and colleagues (1985) measured cotinine levels in smokers receiving various doses of intravenous nicotine, simulating cigarette smoking, for 4 days. They described the relationship: [steady state plasma cotinine concentration] (ng/mL) = (0.783) x [daily nicotine uptake] (ug/kg/day). With such data, a 70 kg nonsmoker with a plasma cotinine concentration of 2.5 ng/mL would have an estimated uptake of 3.2 pg nicotine/ kg/day, or 215 0.22 mg nicotine/day, equivalent to one-fifth of a cigarette. This approach assumes that the half-life for cotinine and nicotine eliminations is similar in smokers and nonsmokers, an assumption that may not be correct (Kyerematen et al. 1982). A third approach is to compare cotinine levels in nonsmokers with those in smokers. Jarvis and colleagues (1984) measured plasma, saliva, and urine nicotine and cotinine levels in 100 nonsmokers selected from outpatient medical clinics and in 94 smokers. Ratios of average values for nonsmokers compared with smokers were as follows: plasma cotinine, 0.5 percent; saliva cotinine, 0.5 percent; urine cotinine, 0.4 percent; urine nicotine, 0.5 percent; and saliva nicotine, 0.7 percent. These data suggest that, on average, nonsmok- ers absorb 0.5 percent of the amount of nicotine absorbed by smokers. Assuming that the average smoker consumes 30 mg nicotine per day (Benowitz and Jacob 1984), this ratio predicts an exposure of 0.15 mg nicotine, or one-sixth of a cigarette per day. The most heavily exposed group of nonsmokers had levels almost twice the overall mean for nonsmokers, indicating that their exposure was :quivalent to one-fourth of a cigarette per day. Most studies (see Tables 6 and 7) report similar ratios when comparing nonsmokers with smokers. The exception is Matsukura and colleagues (1984), who reported urine cotinine ratios of nonsmokers to smokers of 6 percent. The reason for such high values in this one study is unknown. Personal air monitoring data for nicotine exposure can also be used to estimate nicotine uptake. For example, Muramatsu and colleagues (1984) used a pocketable personal air monitor to study environmental nicotine exposures in various living environments. They reported air levels of from 2 to 48 pg nicotine/m*. Assuming that respiration is 0.48 m* per hour and exposure is for 8 hours per day, nicotine uptake is estimated to range from 8 to 320 pg per day. The average values are consistent with other estimates of one-sixth to one-third cigarette equivalents per day in general populations of nonsmokers exposed to ETS. As noted before, these estimates must be interpreted with caution. Relative absorption of nicotine in smokers and nonsmokers may substantially underestimate exposure to other components of ETS. Conclusions 1. Absorption of tobacco-specific smoke constituents (i.e., nicotine) from environmental tobacco smoke exposures has been docu- mented in a number of samples of the general population of developed countries, suggesting that measurable exposure to environmental tobacco smoke is common. 216 2. Mean levels of nicotine and cotinine in body fluids increase with self-reported ETS e - 3. Because of the stability of cotinine levels measured at different times during exposure and the availability of noninvasive sampling techniques, cotinine appears to be the short-term marker of choice in epidemiological studies, 4. Both mathematical modeling techniques and experimental data suggest that 10 to 20 percent of the particulate fraction of sidestream smoke would be deposited in the airway. 5. 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CHAPTER 5 TOXICITY, ACUTE IRRITANT EFFECTS, AND CARCINOGENICITY OF ENVIRONMENTAL TOBACCO SMOKE CONTENTS Irritation: Acute Exposure Irritants in Environmental Tobacco Smoke Irritating and Annoying Effects of Environmental Tobacco Smoke Studies of Healthy Individuals Field Studies Experimental Studies Studies of Sensitive Individuals Children Allergic Individuals Effects on the Lung Effects of Cigarette Smoking on Respiratory Epitheli- um: Studies in Humans Effect of Cigarette Smoking on Lung Inflammatory Cells Studies in Humans Experimental Models Effects of Cigarette Smoking on Lung Parenchyma: Studies in Humans Summary of Lung Effects Carcinogenicity of Environmental Tobacco Smoke Inhalation Experiments Other In Vivo Bioassays In Vitro Assays Summary of Carcinogenicity Conclusions References 227 Irritation: Acute Exposure Irritants in Environmental Tobacco Smoke Tobacco smoke is a complex aerosol that contains several thousand different constituents (Hoffmann, Haley, Brunnemann 1983). Little is known about the health effects of most of these compounds individually and even less is known about their interactions. Tobacco smoke contains compounds established as irritants, toxins, muta- gens, and carcinogens. The main irritants identified in environmen- tal tobacco smoke (ETS) to date are respirable particulates, certain aldehydes, phenol, ammonia, nitrogen oxides, sulfur dioxide, and toluene. The range of concentrations of these irritants measured in mainstream smoke, in sidestream smoke, and in smoky air under “realistic” and “natural” conditions or as results of field studies is summarized in Table 1. The levels of irritants in air contaminated with ETS vary considerably (Table 1). Some of this variation is due to differences in the number of cigarettes smoked, the amount of ventilation, the adsorptive properties of the surroundings, and measurement meth- odology. Triebig and Zober (1984) compared the measured concentra- tions of these irritants with the maximum permissible concentration (MAK) values for working areas and the maximum emission concentration (MIK) values for outdoor air pollution in the Federal Republic of Germany. They concluded that concentrations approxi- mating or in excess of the MIK values can be found for respirable particulates, nitrogen dioxide, and acrolein. The other irritants generally do not reach the existing threshold limit values under realistic conditions. For phenol there is no MIK value. An evaluation of the hygienic and medical importance of the compounds in ETS based on threshold limit values is problematic for two reasons: first, MAK values for industries are established for healthy adults with an 8-hour exposure per day; MIK values are for the outdoor environ- ment, and no indoor limit values exist for “everyday life.” Second, the threshold limit values are valid only for single compounds; ETS contains many different irritants, which might interact to produce more toxicity than anticipated from the concentrations of individual compounds. Many of the constituents of tobacco smoke are also produced by other sources that contribute contaminants to the indoor or outdoor environment. For example, sources unrelated to smoking such as urea formaldehyde foam insulation or certain wood materials can emit formaldehyde and may give rise to mean air concentrations as high as 100 to 400 ppb (Triebig and Zober 1984). In measuring the contribution of tobacco smoke to the levels of these constituents, some researchers (Weber et al. 1979a; Weber and Fischer 1980) have subtracted the measured indoor concentrations from the levels 229 TABLE 1.—Major irritants in environmental tobacco smoke (ETS), their concentrations in mainstream smoke (MS), sidestream smoke (SS) to mainstream smoke (MS) ratios, and levels in smoky air under realistic and natural conditions MS SS/MS Smoky air Irritant (per cigarette) (ratio) (range) Acrolein 10-140 pe 10-20 6-120 ppb Formaldehyde 20-90 pg = 50 30-60 ppb* (CO: 1-43 pbb) Ammonia 10-500 pg 44-100 1000-4580 pbb> Nitrogen oxides 16-600 pg 4.7-50 1-370 ppb NO< 0-50 pbb NO,< Pyridine 32 ug 10 NA¢d Sulfur dioxide 1-75 ppb NA 1-69 ppb< Phenol 20-150 pg 26 74-115 pg/m? Toluene 108 pg 5.6 0.04-1.04 mg/m* Respirable particulates 0.1-40 mg 13-19 55-962 mg/m? « Measured under experimental conditions only. » Fischer (1979). © Difference: indoor concentration minus control value (unoccupied room or outdoors). 4NA = not available. SOURCE: Data from Collishaw et al. (1984), Remmer (1985), Triebig and Zober (1984), US DHHS (1984), except where noted. measured either in the unoccupied room or in the outdoor environ- ment near the room. The measured concentrations of irritants listed in Table 1 are primarily the mean values in air samples collected over intervals of one-half hour to several hours. Substantial variation in levels can occur, depending on the proximity to a smoker and the air-mixing conditions in the room. Weber and Fischer (1983) measured peak concentrations of 3,330 to 99,680 ng/m° for the particulates and 41 to 750 ppb for nitrogen oxide in the “blowing cloud” 1 meter from the smoker immediately after smoke exhalation. These high concentra- tions decreased very rapidly with time (half-life between 2 and 20 seconds) and distance from the smoker. Ayer and Yeager (1982) measured formaldehyde and acrolein concentrations in the side- stream smoke plume rising from a cigarette between puffs and obtained concentrations of some constituents up to three orders of magnitude above the occupational limits established for more extended exposures. 230 Te ae ee ee ce ee ee ee me cee ee ee ee Nitrogen dioxide Particulates FIGURE 1.—Places of impact, and irritants in the eyes and respiratory tract in relation to water solubility SOURCE: Valentin (1986). Irritating and Annoying Effects of Environmental Tobacco Smoke The main effects of the irritants present in ETS occur in the conjunctiva of the eyes and in the mucous membranes of the nose, throat, and lower respiratory tract. The main ocular symptoms are reddening, itching, and increased lachrymation; the main respira- tory tract symptoms are itching, cough, and sore throat. The relationship of the site of the effect of some irritants in the eyes and in the respiratory tract to their water solubility is illustrated in Figure 1. The penetration of the particulates into the lung depends on their size; because most of the particulates in tobacco smoke are smaller than 1 um, they can penetrate to the smallest airways. Studies of Healthy Individuals Field Studies Several studies have shown that annoyance and irritation are the most common acute effects of ETS exposure. Shephard and Labarre (1978) surveyed more than 1,000 Canadian citizens aged 10 to 80 years. The interviewed population was representative of southern 231 Ontario with respect to both income and profession but underrepre- sentative of the elderly. Seventy-three percent of the nonsmokers were disturbed by tobacco smoke in restaurants and 53 percent by tobacco smoke in offices. The most frequently reported symptom was eye irritation. Complaints of nausea, dizziness, and wheezing as well as rhinorrhea were also reported, although much less frequently than stinging eyes. Similar results were obtained in a survey conducted in three restaurants in Switzerland (Weber et al. 1979a). A multiple-choice questionnaire was administered to 220 guests. One-third to two- thirds of the respondents complained about air quality, and up to 12 percent reported eye irritation. In another survey of more than 2,100 white-collar employees, Barad (1979) found that nearly one-fourth of the nonsmokers reacted to smoke exposure with frustration and hostility. Weber and Fischer (1980) surveyed employees in 44 worksite workrooms, located in seven different companies, that included offices, rooms for design and technical and clerical work, and conference rooms. The choice of companies and worksites was based on availability and therefore was not a random sample. In all workrooms, the concentrations of carbon monoxide (CO), nitrogen oxide (NO), acrolein, particulate matter (PM), and nicotine were measured in the air. The contribution of tobacco smoke to these levels was obtained by subtracting background levels obtained before working hours from the concentrations during working hours. These differences from the background levels were called 8CO, 5NO, and so on. Measurements were conducted in each room on 2 successive days (12 1-hour mean values per workroom), and 472 employees were questioned about irritation and annoyance as well as about their opinions on involuntary smoking. Some of the exposure results are summarized in Table 2. The comparison of these 5 values with the measured absolute indoor concentrations revealed that 30 to 70 percent of the measured indoor concentrations of carbon monoxide, nitrogen oxide, and particulate matter were due to tobacco smoke. The correlations between the gas phase components &CO and 8NO were relatively high (Pearson correlation coefficient r=0.73). However, the correlations of 5CO with dnicotine and 5PM were low. Nicotine values were generally in the range of the lower detection limit of the method of measurement used (gas chromatography). The low correlation of the gaseous components with the particulate matter is probably due to the different physical properties (sedimentation, adsorption, and desorp- tion of the particulates) and to the fact that the 8PM values include particulates from sources other than tobacco smoke. Approximately one-third of the employees described the quality of air at work as “bad” with regard to tobacco smoke. Forty percent 232 workrooms Number of Mean Standard Component samples values deviation Maximum 5Carbon monoxide (ppm) 353 11 13 6.5 5Nitrogen oxide (ppb) 348 32 60 280 Particulate matter (g/m?) 429 133 130 962 &Nicotine (g/m?) 140 09 19 13.8 ment questionnaire was given to approximately 1,100 employees working in nine buildings. Data were analyzed according to the smoking habits of the respondents and the office rules regulating smoking. The distribution of the responses to questions assessing the presence of symptoms (headache; fatigue; nose, throat, and eye irritations; sore throat and cold Symptoms) were similar in environ- ventilation. The researchers used a “building illness index” that included several different symptoms in addition to irritation (eg, The influence of the temperature and humidity of room air on odor perception and irritation was investigated by Kerka and Humphrey (1956). They found that odor intensity was somewhat reduced by increasing the temperature at a constant humidity. Both odor and irritation intensity were reduced by increasing the humidity. Johansson and Ronge (1966) also observed that acute irritation is increased in warm and dry air. Johansson (1976) exposed 12 subjects in a 6.7 m® climatic chamber for 29 minutes to the ETS produced by the smoking of 10 cigarettes. The air in the chamber was cold (18° or 19° C) or warm (25° or 26° C), and at each temperature, the relative humidity was evaluated at three levels from 30 to 80 percent. Under all conditions, subjective irritation, assessed by a questionnaire, increased during exposure; eye irritation increased more than nose irritation. No marked effect of temperature on the degree of irritation was observed, probably owing to the limited temperature range studied (18° to 26° C). Kerka and Humphrey (1956) demon- strated a thermal effect when the temperature range was greater than 8° C. The low relative humidity (7 to 20 percent) in aircraft may be responsible for the substantial level of perceived irritation due to TS among passengers, despite the low levels of pollutants measured n aircraft (WHO 1984). Basu and colleagues (1978) studied the effects of ETS on human tear film and observed a reduction in the stability of the precorneal tear film in subjects exposed to a smoke concentration corresponding to approximately 20 ppm CO. In the presence of ETS, the tear film breakup time was significantly reduced by 35 to 40 percent com- pared with baseline measurements without smoke. The researchers suggested that this reflects an alteration in the relative proportions of the constituents of tear film. In these studies, the quantitative exposures to ETS either were not measured or were determined in a relatively imprecise way. More systematic studies, including measurements of several compounds of ETS, were carried out by Weber and collaborators (Weber et al. 1976, 1979a,b; Weber, Fischer, Grandjean 1977; Weber, Fischer, Gierer et al. 1977; Weber and Fischer 1983) and Muramatsu, Weber, and colleagues (1983). These experiments were carried out in a climatic chamber of 30 m°, with an air temperature of 20° to 24° C anda relative humidity between 40 and 60 percent. The ventilation rate could be varied between 0.1 and 16 air changes per hour. The smoke was produced by a Borgwald smoking machine under standardized conditions, and only the sidestream smoke of cigarettes was used. Healthy students were exposed to the sidestream smoke of cigarettes in groups of two or three in the climatic chamber. They all also participated in a control exposure with identical. conditions, but without sidestream smoke in the air. The concentrations of the following compounds were continuously recorded: carbon monoxide, 234 considered an objective measure for eye irritation. In the first study, 33 subjects were exposed to continuously increasing smoke concentrations (Weber et al. 1976). The main results are summarized in Figure 2. The concentrations of CO, NO, formaldehyde (HCHO), and acrolein increased with the number of cigarettes smoked. Both mean subjective eye irritation and mean eye blink rate increased with increasing smoke concentration. Subjective nose and throat irritation was also evaluated. Nasal symptoms were less pronounced than eye symptoms, and the throat was the least affected. In a second series of studies, acute effects were analyzed in relation to smoke concentration and duration of exposure (Weber et al. 1979; Muramatsu, Weber et al. 1983). The tobacco smoke concentrations corresponded to 1.3, 2.5, 5, and 10 ppm CO (8CO). Subjects were exposed to these smoke concentrations for 1 hour, each smoke concentration increasing linearly during the first 5 to 10 minutes and then remaining constant at the desired level for the rest of the hour. Because very high correlations (r>0.9) were obtained in the first experimental series between SCO and each of the other compounds, only &CO was used to quantify the level of exposure to ETS. The results obtained for subjective eye irritation and eye blink rate are shown in Figures 3 and 4. The mean reported level of eye irritation as well as the eye blink rate increased with increasing smoke concentration. Both irritation parameters also increased with the duration of exposure under conditions of constant smoke concentration. The same, but less pronounced, results were observed for nose and throat irritation. Annoyance increased rapidly as soon as smoke production began and increased with increasing smoke concentration, but after 10 to 15 minutes the level of annoyance remained approximately constant during the rest of the exposure. Thus, the intensity of exposure was important in determining the degree of annoyance and the duration of exposure was less important. These experiments demonstrated an objective irritant response in healthy adult subjects at levels of smoke exposure substantially lower than the levels at which an airway response has been demonstrated. Whether this difference represents a difference in threshold for irritation in the eye and airway or a limitation in the ability to measure subtle changes in the airway is uncertain. 235 Eye irritation Eye blink rate/min Very strong 5 7 - 80 Strong 4 ” - 60 & Medium 3-4 re 40 Weak 2- - 20 None 1- L 0 min ] T aco 1 11 22 32 42 43 ppm t q t { J q SNO 0.08 0.42 0.77 1.11 1,45 1.50 ppm I q q t ' J SHCHO 0.03 0.18 0.32 0.47 = 0.62 0.64 ppm i J ' q t ( AAcrolein 0 0.05 0.11 0.16 0.20 0.20 ppm No. of cigarettes 0 10 20 ames Eye irritation index aveveee Eye blink rate FIGURE 2.—Mean subjective eye irritation, mean eye blink rate, and concentrations of some pollutants during continuous smoke protection in an unventilated climatic chamber NOTE: 33 subjects; 0 min: measurement before smoke production. SOURCE: Weber et al. (1976). Hugod and colleagues (1978) and Weber and colleagues (Weber, Fischer, Grandjean 1977; Weber, Fischer, Gierer et al. 1977; Weber et al. 1979b) carried out several experiments in order to determine which compounds in ETS are responsible for irritation and annoy- ance. The results of the two studies were somewhat conflicting. Hugod and colleagues exposed 10 subjects in an unventilated 68 m*° room to high concentrations of sidestream smoke (concentrations corresponding to 20 ppm CO), to the gas phase of sidestream smoke alone, and to acrolein alone at concentrations three times those found in sidestream smoke alone. Irritation was assessed via a 236 34 Eye irritation index Smoke concentration (Delta carbon monoxide) Fe es ee 10 ppm ACO § / = 5Sppmasco E 7 “ 3 24 8 2.5 ppm ACO 1.3 ppm ACO Oe ea een es — Control 1! 60 (min) Exposure duration FIGURE 3.—Mean subjective eye irritation related to smoke concentrations (ppm delta CO) and duration of exposure NOTE: 32 to 43 subjects; 0 min: measurement before smoke concentration; 6 to 60 min: constant smoke production. SOURCE: Muramatsu, Weber et al. (1983). questionnaire. Both annoyance and irritation were reported at similar levels in the subjects exposed to the whole sidestream smoke or to the gas phase only. Exposure to acrolein caused only slight discomfort. Weber and colleagues (Weber, Fischer, Grandjean 1977; Weber, Fischer, Gierer et al. 1977; Weber et al. 1979b) exposed students in groups of two or three in a 30 m® climatic chamber to whole sidestream smoke, to acrolein alone, to formaldehyde alone, or to the gas phase of smoke. Subjective irritation and annoyance as well as eye blink rate were measured. The results indicated that acrolein and formaldehyde did not produce substantial irritation or annoy- ance at the levels used. The gas phase exposure resulted in high levels of reported annoyance, but was less important as a determi- nant of irritation. The objectively measured eye blink rate, as well as subjective eye irritation, was much lower with the gas phase alone Production; 0 to 5 min; increasing amoke 237 40.0 7 Eye blink rate Smoke concentration (deita carbon monoxide) 35.0 + a ™ 10 ppm ACO f \ “” - / Ww / 30.0 4 / o / ” ““== 5 ppm ACO 2 / 7 “” € 5 25.0 = 2 £ a 2.5 ppm ACO 20.0 + 1.3 ppm 4CO a_ ——-—-—- Control 15.0 4 0.0 J c T T T T T 1 0 10 20 30 40 50 60 (min) Exposure duration FIGURE 4.—Mean effects of environmental tobacco smoke on eye blink rate NOTE: 32 to 43 subjects; 0 min: measurement before smoke production; 0 to 5 min: increasing smoke concentration; 6 to 60 min: constant smoke production. SOURCE: Muramatsu, Weber et al. (1983). than with the total sidestream smoke, suggesting that the particu- late phase is the major determinant of irritation. The researchers postulated that the irritating effects of the particulate phase are due to the semivolatile irritant conpounds. These compounds, which volatilize rapidly during the process of combustion, recondense on the particulates with cooling and may deposit irritants in relatively high concentrations on the mucous membranes. 238 Studies of Sensitive Individuals Children Fischer (1980) observed that employees suffering from hay fever reported significantly more eye irritation at work than those without hay fever. Effects on the Lung Cigarette smoking is associated with Prominent changes in the numbers, types, and functions of respiratory epithelial and inflam- exposure to environmental tobacco smoke on lung structure and biochemistry have not been conducted, this Section reviews those studies in humans and animals that Provide evidence on smoke exposures that may be relevant to ETS exposure. Extensive evidence shows that exposure to cigarette smoke has adverse effects on respiratory epithelial cells, and dose-response relationships have been established from these changes (Auerbach et al. 1961; Auerbach, Hammond, Garfinkel 1970). Studies involving the systematic examination of the bronchial mucosa from large TABLE 3.—Sections with one or more epithelial changes, by packs of cigarettes per day Total with one or more changes Number of Number of re Group subjects sections Number Percentage Subjects without lung cancer Never smoked regularly 65 3,324 559 168 Smoked <1/2 pack/day 36 1,824 1,683 92.3 Smoked 1/2-1 pack/day 59 3,016 2,938 97.4 Smoked 1-2 pack/day 143 7,062 7,021 99.4 Smoked >2 pack/day 36 1,787 1,780 99.6 Subjects with lung cancer 63 2,784 2,778 99.8 Totals 402 19,797 16,759 Average 84.7 SOURCE: Auerbach et al. (1961). epithelium of the men who had smoked had epithelial changes. The most common abnormality observed was atypical nuclei, and a large proportion of sections had hyperplasia. Denudation of the ciliated epithelium was also present in most of those who had smoked. Other studies have observed that goblet cells were frequently increased in the airways of cigarette smokers (Regland et al. 1976; Jones 1981). The extent and severity of the abnormalities have been closely related to the intensity of smoking. A similar relationship of smoking habits to laryngeal lesions has been observed (Auerbach, Hammond, Garfinkel 1970), although the laryngeal lesions were less frequent and less advanced than those in the bronchi for a given smoking history. The frequency and severity of epithelial lesions observed in smokers contrasts sharply with those in individuals who do not smoke regularly. In the study by Auerbach and colleagues (1961) (Table 3), 98 percent of the sections from the tracheobronchial tree from smokers contained abnormal epithelial changes; however, similar changes were observed in only 16.8 percent of the sections from nonsmokers. The most common lesion in nonsmokers was epithelial hyperplasia (9.4 percent); atypical cells were seen in only 4.8 percent of the sections from nonsmokers. If it is assumed that the nonsmoking group included a subgroup of individuals who were chronically exposed to environmental tobacco smoke, an assumption that seems reasonable in light of the largely U.S. veteran population under consideration in the Auerbach group’s study, then some information on the effect of chronic exposure to environmental tobacco smoke on the respiratory epithe- 240 may occur in some nonsmokers, but these findings are not common in the majority of nonsmokers. rn Cigarette smoking also has adverse effects on the bronchial wall beneath the epithelium. Submucogal gland hypertrophy has been observed frequently (Auerbach et al. 1961; Regiand et al. 1976; Jones 1981). The prevalence is related to the intensity of cigarette smoking. Mucous gland hypertrophy is seen in nonsmokers, but. da not prevalent and is usually not extensive (Auerbach et al. 1961). .. . The loss of ciliary epithelium, the increased | numbers..of ‘goblet cells, and the mucous gland hypertrophy frequently observed in cigarette smokers would predict mucociliary dysfunction. Indeed, available evidence indicates that long-term cigarette smoking. im- pairs mucociliary transport (Wanner 1977). Once a cigarette smoker develops chronic bronchitis, mucus transport appears to be irrevers- ibly damaged. Impairment persists even in patients who have abstained from cigarette smoking for many years (Santa Cruz et al. 1974). Prior to the development of chronic bronchitis, however, partial recovery of function has been observed (Camner et al. 1973). Studies examining mucociliary dysfunction in humans due solely to chronic environmental smoke exposure have not been reported. Effect of Cigarette Smoking on Lung Inflammatory Cells _ Studies in Humans . One of the earliest pathologic lesions found in the lungs of young smokers is a respiratory bronchiolitis (Anderson and Foraker 1961; McLaughlin and Tueller 1971; Niewoehner et al. 1974). Clusters of pigment-laden phagocytes, predominantly alveolar macrophages (AM), lodge in the respiratory bronchioles of cigarette smokers precisely at the sites of the earliest lung injury. The infiltration’ by AM precedes the development of emphysema and focal fibrosis (Cosio et al. 1978). Analyses of cells harvested by bronchoalveolar lavage complement the morphologic studies, Lavage fluid yields five to seven times more AM from the lungs of cigarette smokers than from nonsmokers’ lungs (Harris et al. 1970; Reynolds and Newball 1974; Warr et al. 1976; Hunninghake et al. 1979; Hoidal et al. 1981). The alveolar macrophages from smokers appear to be activated morphologically and metabolically. The AM from smokers have increased size, endoplasmic reticulum, Golgi apparatus, glucose metabolism, hydrolytic and proteolytic enzyme activities (Pratt et al. 1971; Cohen and Cline 1971; Harris et al. 1970; Rodriguez et al. 1977; Hinman et al. 1980; Martin 1973; Cantrell et al. 1973), and increased rates of oxidative metabolism resulting in increased production of reactive oxygen species (superoxide radical, hydrogen peroxide, and hydroxy] radical) (Hoidal et al. 1981; Hoidal and Niewoehner 1982), 241 The strategic location of the alveolar macrophages and their altered function have led to the hypothesis that they may contribute to the alteration of the protease—antiprotease balance of the lower respiratory tract and thus foster the development of emphysema in smokers. Two plausible mechanisms have been identified by which AM may influence the protease—antiprotease balance in cigarette smokers. The first is by directly increasing the lung protease burden. Human AM release enzymes with elastolytic activity in vitro, whereas those from nonsmokers do not (Rodriguez et al. 1977). The activity may originate from endogenous or exogenous sources. A metalloenzyme with activity against synthetic amide substrates, which have specificity for elastase, was detected in the bronchoalveo- lar washings of cigarette smokers (Janoff et al. 1983; Niederman et al. 1984) and was also found in the cell culture fluid of smokers’ AM (Hinman et al. 1980). Alveolar macrophages can synthesize a metalloprotease capable of solubilizing elastin; they also contain a thiolprotease with such activity (Chapman and Stone 1984). The metalloprotease, if analogous to that of murine macrophage elastase, would be resistant to inactivation by alpha,-protease inhibitor (a,PD (Banda et al. 1980). These enzymes have not been demonstrated to cause emphysema. The content of elastolytic activity in AM at a given time is less than that of equal numbers of polymorphonuclear leukocytes (PMN); thus, AM may be only a minor source of enzymes capable of lung parenchymal destruction. However, their potential importance must be considered in light of their demonstrated ability to degrade elastin in the presence of serum protease inhibitors (Chapman and Stone 1984) and their capability of ongoing synthesis of elastolytic enzymes. Cell matrix contact may be critical for their matrix-degrading action, since the AM-derived enzymes are likely to be membrane bound. Human AM also acquire elastolytic activity from exogenous sources. AM can bind and internalize neutrophil elastase by virtue of possessing a specific membrane receptor for this and other neutro- phil glycoproteins (Campbell et al. 1979; Campbell 1982; McGowan et al. 1983). Studies to date suggest that the scavenged elastase accounts for much of the elastolytic activity in AM lysates. Seques- tered PMN elastase may subsequently be released by AM over an extended period of time. The second mechanism by which AM may influence the protease— antiprotease balance in cigarette smokers is by inactivating o,PI, a major antiprotease of the lower respiratory tract in humans (Gadek et al. 1981). Smokers’ AM can inactivate a,PI through oxidant mechanisms in vitro (Carp and Janoff 1980). Studies on bronchoal- veolar lavage fluids have identified oxidatively inactivated a,PI in some human smokers (Gadek et al. 1979; Carp et al. 1982), but this has not been a consistent finding (Stone et al. 1986; Boudier et al. 242 The phagocytic capabilities of AM from cigarette smokers and nonsmokers are similar in most studies (Harris et al. 1970; Cohen and Cline 1971; Reynolds et al. 1975; Territo and Golde 1979), although a few studies (Martin and Warr 19’ 7; Fisher et al. 1982) have suggested a modest decrease in the phagocytic abilities of AM from smokers. The experimental design: of. ‘studies has differed considerably, and technical factors may be responsible for the variable results. In particular, there are differences in cellular culture conditions. In view of the increased number of AM in cigarette smokers, it seems unlikely that a primary phagocytic defect of AM would account for the bacterial colonization observed in. some. cigarette smokers. . _ The possibility that increased numbers of PMN may be present in the lungs of cigarette smokers has been examined primarily because of the attention given these cells in the study of the pathogenesis of emphysema. PMN elastase is the only purified human enzyme with ready access to the lung parenchyma that has been demonstrated to. cause emphysema when administered to animals, The number: of PMN is increased in the distal airways and lung parenchyma of cigarette smokers. Bronchoalveolar lavage from some smokers yields increased PMN (Reynolds and Newball 1974; Hunninghake et.al. 1979). More compelling evidence for increased PMN in the lungs of smokers comes from the morphologic evaluation and direct cellular. analysis of the lung parenchyma. A fourfold increase in PMN infiltration has been observed in the lungs of cigarette smokers compared with the lungs of nonsmokers, using morphometric techniques (Ludwig et al. 1985). Analysis of cell suspensions from lung biopsies has also demonstrated increased PMN in the. hung parenchyma of smokers (Hunninghake and ‘Crystal 1983). The alveolar septa are the primary site of the PMN accumulation. Increased PMN are present in the alveolar walls of smokers both with and without emphysema, which suggests that other factors must also be involved in the development of the destructive lesion. Factors that might influence the destruction of lung parenchyma by PMN elastase include the intensity of PMN influx, the amount of elastase per cell, the quantity and site of elastase released, and local factors that enhance or inhibit the elastolytic activity. Investigations of the relation of PMN elastase levels and the development of emphysema have provided discrepant results. Some studies have shown elevated levels of PMN elastase in patients with chronic obstructive pulmonary disease (Galdston et al. 1977; Rodriquez et al. 1979; Kramps et al. 1980), but others have not (Taylor and Keuppers 1977; Abboud et al. 1979). Other alterations in the PMN function of 243 cigarette smokers include the enhanced generation of reactive oxygen species in certain smokers (Ludwig and Hoidal 1982). After stimulation, the release of superoxide anion by PMN was 50 percent greater from smokers with peripheral white blood counts (WBC) greater than 9,000 per mm? than from nonsmokers with similar WBC or from smokers or nonsmokers with WBC less than 9,000 per mm*. (Cigarette smokers have increased peripheral WBC counts compared with nonsmokers.) The influence of cigarette smoking on many aspects of the immune system has been examined. Immunoglobulin (Ig) levels in the peripheral blood of smokers have been reported to be decreased (Gerrard et al. 1980; Ferson et al. 1979), but similar results have not been observed in all studies (Bell et al. 1981; Merrill et al. 1985). In contrast to the decrease of IgG in peripheral blood, cigarette smokers appear to have increased IgG levels in bronchoalveolar lavage fluid (Bell et al. 1981), primarily owing to an increase in IgG, (Merrill et al. 1985). Cell-mediated immunity may also be affected by cigarette smoking, but again, the results are somewhat conflicting. Peripheral blood T-lymphocytes and mitogen responsiveness have been reported to be increased (Silverman et al. 1975), unchanged (Daniele et al. 1977), or decreased (Petersen et al. 1983). Natural killer-cell activity in the peripheral blood of cigarette smokers appears decreased (Ginns et al. 1985; Ferson et al. 1979). Analysis of peripheral blood lymphocyte populations by monoclonal antibodies has demonstrated increased T-lymphocytes (OKT3+), with a decreased proportion of OKT4+ (helper/inducer), and an increased proportion of OKT8+ (suppressor/cytotoxic) subsets in smokers with greater than 50 pack- years of smoking (Miller et al. 1982). Analysis of bronchoalveolar lavage fluid from cigarette smokers with a mean smoking history of 14 ~-__ 9 pack-years demonstrated a decreased proportion of OKT4+ lymphocytes and an increased proportion of OKT8+ lymphocytes (Costabel et al. 1986). In the latter study, the alterations in T-lymphocyte subsets observed in bronchoalveolar lavage were not present in peripheral blood. This finding and the increase in IgG in bronchoalveolar lavage fluid, but not in serum, raise the possibility of regional effects of cigarette smoking on the immune system. The extent to which the alterations of inflammatory cell numbers and functions observed in smokers are also present in individuals who are chronically exposed to environmental tobacco smoke remains unknown. Studies in humans have not directly addressed this issue. Studies of dose-response relationships are absent, except for those cited that document a relationship of peripheral white blood cell count and lymphocyte T-cell subsets. If it is assumed that a subgroup of nonsmokers is composed of individuals who are chroni- cally exposed to environmental tobacco smoke, then some inferences 244 are possible. As has been stated, the most common pathologic feature in the lungs of young cigarette smokers is an accumulation of pigment-laden macrophages in the respiratory bronchioles. In the study by Niewoehner and colleagues (1974), all 19 male cigarette smokers who died suddenly elsewhere than in a hospital had such lesions, which were present in all sections studied in 16 of the 19 subjects. In contrast, only 5 of 20 nonsmokers had similar lesions, and they were minimal in all but 2. One of the two individuals was a stoker in a foundry and the other was undergoing desensitization for severe hay fever. Although the inflammatory cell accumulation cannot be absolutely attributed to these extenuating circumstances, it is clear that the respiratory bronchiolitis is not common in young, healthy individuals who do not smoke regularly. In contrast, autopsy studies have observed focal inflammatory changes quite frequently in older subjects who had not smoked, but the lesions were of much less severity than in age-matched subjects who had smoked (Cosio et al. 1978). Similar changes have not been observed in studies on bronchoalveolar lavage fluids. The metabolic activation of the AM from younger and older nonsmokers is similar (Hoidal and Niewoeh- ner 1982). These findings suggest that the characteristic inflammato- ry lesions seen in the lungs of smokers are usually absent or are modest in those individuals who do not smoke cigarettes and who are not exposed to an alternative inciting agent. Experimental Models The effect of cigarette smoke inhalation on lung inflammation and inflammatory cell function has been extensively studied in experi- mental animal models; however, studies have not investigated inflammatory cell alterations in models intended to simulate chronic environmental tobacco smoke exposure. Several studies have demon- strated that chronic cigarette smoke exposure produces an accumu- lation of AM within the respiratory bronchioles of many animal species, including dogs (Hernandez et al. 1966; Frasca et al. 1971, 1983; Park et al. 1977), rats (Kendrick et al. 1976; Coggins et al. 1980; Huber et al. 1981), hamsters (Bernfeld et al. 1979; Hoidal and Niewoehner 1982), and mice (Matulionis and Traurig 1977), that is strikingly similar to that seen in human smokers. In most studies, the accumulation of AM has been dependent on the duration and intensity of the smoke exposure (Hoidal and Niewoehner 1982; Huber et al. 1981). Increases in lysosomal enzyme activities have been observed in rats (Etherton et al. 1979) and mice (Matulionis and Traurig 1977) following tobacco smoke exposure. Increased elastase secretion by alveolar macrophages from mice chronically exposed to cigarette smoke has also been observed (White et al. 1979). Oxygen consumption, superoxide anion release, hydrogen peroxide produc- tion, and hexose monophosphate shunt activity were reported to be 245 increased in AM harvested by bronchoalveolar lavage from hamsters (Hoidal and Niewoehner 1982) and rats (Drath et al. 1978; Huber et al. 1981) chronically exposed to tobacco smoke. Accumulation of PMN in the alveolar septa of cigarette smoke-exposed hamsters, strikingly similar to that observed in human smokers, has also been reported (Ludwig et al. 1985). In contrast to the focal nature of the AM accumulation, the accumulation of PMN was diffuse. Studies of PMN function have not been systematically evaluated in smoke- exposed animals. One distinctive feature in rats has been a lympho- cytic periairway infiltration (Innes et al. 1956; Huber et al. 1981). Similar alterations are not seen in humans. The lymphocytic infiltration may be due to complicating respiratory infections with mycoplasma or a respiratory virus, which have been common in rats. Effects of Cigarette Smoking on Lung Parenchyma: Studies in Humans The most striking alteration of the lung parenchyma associated with cigarette smoking is centrilobular emphysema. The relation- ships between smoking history, age, and the degree of emphysema have been examined. The effect of smoking on the development of emphysema is believed to be cumulative (Anderson et al. 1972; Auerbach et al. 1974). In a study of 1,824 autopsies from individuals who had died in the hospital, Auerbach and associates, using a semiquantitative scoring system, detected emphysematous lesions in all individuals who had smoked two or more packs of cigarettes per day, including 111 who had been under 60 years of age at the time of death. The extent of emphysema strongly correlated with the number of cigarettes smoked per day. However, some emphysema- tous changes, usually of a mild degree, were noted in 94 percent of the individuals who had regularly smoked less than one-half pack per day. In contrast, no emphysema was detected in 95 percent of the 175 individuals who had not smoked regularly, and only one case of emphysema of moderate severity had occurred in a person who had not smoked. These findings suggest that emphysema is rare in individuals who do not smoke regularly and do not have a genetic predisposition for the disease. Summary of Lung Effects Substantial evidence documents that active cigarette smoking produces adverse effects on respiratory epithelial cells and causes lung inflammation and alveolar septal disruption. Whether these effects occur following chronic exposure to environmental tobacco smoke cannot be definitively answered by the fragmentary data now available. It is possible that clinically significant pulmonary conse- quences of chronic exposure to environmental tobacco smoke in adults might occur only when this exposure interacts with other 246 factors in particularly susceptible individuals. In this regard, future studies directed at selected high-risk populations or animal models incorporating exposure to environmental tobacco smoke along with other exposures might be the most fruitful areas of investigation into the effects of chronic exposure to environmental tobacco smoke. Carcinogenicity of Environmental Tobacco Smoke This section reviews some of the more widely employed methods of evaluation of the carcinogenicity of mainstream smoke that may also be extended to the evaluation of ETS. The similarities, differences, and technical difficulties in employing these various bioassays with MS, smoke condensate, and ETS are discussed. Inhalation Experiments Because inhalation is the primary mode of exposure for both active and involuntary smoking, animal inhalational assays would appear to be the ideal approach to developing an animal system for carcinogenicity testing. However, the acute toxicity (mainly due to carbon monoxide and nicotine) have limited the exposures to whole smoke that can be tolerated by laboratory animals. Two types of passive exposure systems offer the primary ap- proaches to inhalation studies with small laboratory animals. These systems provide either the forced exposure of the whole body to tobacco smoke or exposure of the head only. The amount of smoke that is retained in the lower respiratory tract of the animals is the dosage variable of interest in assessing these studies. The particulate matter content of whole smoke is probably of greater importance than the vapor phase content (Wynder and Hoffmann 1967; Davis et al. 1975) for studies of carcinogenesis. Labeled particulate phase components have been used for determining the deposition of the particulate phase in the respiratory tract in smoke inhalation studies (Mohr and Reznik 1978). However, since such markers are applied to the tobacco column, they may be partially volatilized during smoking. Thus, some of the values reported in deposition studies of inhaled smoke aerosols in mice, rats, and hamsters reflect the deposition of the trapped particulate phase plus the gas phase of cigarette smoke in the respiratory tract. A less ambiguous tracer is decachlorobiphenyl (DCBP). It is added to the tobacco column of cigarettes, and after exposure of the animals to the smoke of the treated cigarettes, this tracer can be determined in extracts of various segments of the respiratory tract by gas chromatography with an electron capture detector (GC-ECD). The detection limit of DCBP is <5 x 101g (Lewis et al. 1973; Hoffmann et al. 1979). Using these techniques, only a small percentage of the smoke particulates of cigarette mainstream smoke can be shown to reach regions in the 247 lower respiratory tract of small laboratory animals. This may explain, at least in part, why the lifetime inhalation exposures of small animals to tobacco smoke have led only to limited numbers of lung tumors. In mice, inhalation assays with cigarette smoke have generally led to hyperplasia and metaplasia in the trachea and bronchi of the animals (Wynder and Hoffmann 1967; Mohr and Reznik 1978). In one of the most extensive studies, the Leuchtenbergers (1970) induced pulmonary adenoma and adenocarcinoma in Snell’s mice. However, only the gas phase, not the total smoke, induced a statistically significant number of lung tumors. In another inhalation bioassay, male and female C57B1 mice (100 in each group) were exposed, nose only, to fresh mainstream smoke diluted with air (1:39) for 12 minutes every other day for the duration of their lives. Four lung tumors were detected in both the treated male mice and the treated female mice. No lung tumors were found among controls. A similar experimental design was used to examine the possible differences between the smoke of flu-cured Bright tobacco cigarettes and the smoke of air-cured Bright tobacco cigarettes (Harris et al. 1974). Female Wistar rats (408 animals) were exposed, nose only, to a 1:5 smoke-to-air mixture for 15 seconds of every minute during an 11-minute exposure twice a day, 5 days per week, for the lifespan of the animals. Three of the rats exposed to cigarette smoke developed pulmonary squamous neoplasms of uncer- tain malignancy and one animal had an invasive squamous-cell carcinoma of the lung. No tumors were found in the 104 sham- control animals or in the 104 untreated female rats (Davis et al. 1975). Fischer-344 rats (80 animals) were exposed, nose only, to a 1:10 smoke-to-air mixture for approximately 30 seconds of every minute that a cigarette was being smoked (Dalbey et al. 1980). In this manner, the animals were exposed to the smoke of one cigarette per hour, 7 hours per day, 5 days per week, for 128 weeks. The mean pulmonary particulate deposition during the smoke-aerosol exposure was 0.25 mg per cigarette, or 1.75 mg per rat per day. Ten respiratory tumors were observed in seven smoke-exposed rats. One alveologenic carcinoma and two adenomatoid lesions were observed in 3 of the 93 control rats employed in this study. A similar protocol was used to evaluate the effects of the inhalation of the smoke of cigarettes with varying tar deliveries. In this study (Wehner et al. 1981), squamous metaplasia of the laryngeal and tracheal epitheli- um was significantly increased in the smoke-exposed Fischer-344 rats. Syrian golden hamsters (80 males and 80 females) were exposed, nose only, to a 1:7 smoke-to-air mixture for 10 to 30 minutes, 5 days per week, for a period no longer than 52 weeks. The incidence of 248 laryngeal leukoplakias ranged from 11.3 percent for the animal receiving the low dose to 30.6 percent for those animals receiving the highest dose of cigarette smoke. Such changes were not observed in the controls or in the hamsters exposed to the gas phase only (Dontenwill 1974). Exposing 102 male BIO 87.20 and BIO 15.16 hamsters, nose only, twice a day, 5 days a week, for up to 100 weeks, resulted in almost 90 percent of the animals having hyperplastic or neoplastic changes in the larynx (Bernfeld et al. 1974). Laryngeal cancer was five times more frequent in the BIO 15.16 strain. Two animals in this strain also developed nasopharyngeal tumors. Another study using nose-only exposures and similar extents of exposure reported similar changes in the larynx of the smoke- exposed animals (Wehner et al. 1974). Increasing the exposure duration to the lifespan of the animals resulted in the development of squamous papilloma of the larynx. Thirty rabbits in an inhalation chamber were exposed to the smoke generated from 20 cigarettes for up to 5 1/2 years. Thirty-one animals were used as controls. No tumors were found among the treated animals that could be related to the exposure to cigarette smoke (Holland et al. 1963). Eighty-six beagle dogs, trained to inhale cigarette smoke through tracheostomata, were actively exposed to smoke from either filter or nonfilter cigarettes (Auerbach, Hammond, Kirman et al. 1970). Tumors of the lung were reported in 23 of the 62 dogs exposed to smoke from the nonfilter cigarettes. Two of the dogs in this group had small bronchial carcinomas. Noninvasive bronchioalveolar tumors were reported in 4 of the 12 dogs exposed to the smoke of filter cigarettes and in 2 of the 8 control dogs. The bronchioalveolar tumors tended to be multiple, with as many as 20 per lung, and were reported in 40 of the 203 lung lobes in the 29 dogs with such tumors. Inhalation studies with SS or ETS have not been reported thus far with any of the laboratory animal inhalational assays. This lack of experiments has in large part been due to the absence of exposure devices that allow the appropriate delivery of the inhalant without incurring the loss of the test animals due to the toxicity of carbon monoxide and nicotine. Other In Vivo Bioassays Among alternative methods used to assess the relative carcinoge- nicity of mainstream cigarette smoke, the most widely utilized test is to collect the cigarette smoke condensate (CSC) and to bioassay this material for carcinogenicity. In the process of preparing CSC, many of the volatile and semivolatile components are lost. Furthermore, there are serious concerns regarding the influence of aging of the CSC, which can affect both the chemical composition and the biological activity. Despite these shortcomings, bioassays using CSC 249 have provided insight into mechanisms by which tumor induction in animal tissues is likely to occur. The application of CSC to mouse skin has helped to identify those agents that are active as tumor initiators and has shown that within the CSC subfractions are components that can act as tumor promoters or cocarcinogens, respectively. Thus, this approach allows the comparison of various condensates, especially when large groups of animals are used (>50 per group). The application of CSC to mouse skin is the most widely employed assay for the evaluation of its carcinogenic potential. The mouse skin bioassays in tobacco carcinogenesis have been reviewed (Hoffmann, Wynder et al. 1983). A typical experiment uses two to three dose levels of condensate, generally 25, 50, and 75 mg of CSC, which are administered topically to the shaved backs of mice three to six times weekly for approximately 78 weeks. The CSC is most frequently applied as an acetone suspension (25, 33, or 50 percent). At the conclusion of such a study, skin tumors, some of which are malignant, generally are observed among the treated animals in a dose-related fashion. Such studies have shown that the carcinogenic activity of CSC is also a function of tobacco variety, is influenced by replacement materials such as tobacco sheet or semisynthetics, and may be influenced by the use of additives. Although such bioassays have been extensively performed for the tars from mainstream cigarette smoke, only one study has examined the carcinogenic potential of the condensate of sidestream cigarette smoke. Cigarette tar from the sidestream smoke of nonfilter cigarettes that had settled on the funnel covering a multiple-unit smoking machine was suspended in acetone and applied to mouse skin for 15 months (Wynder and Hoffmann 1967). Out of a group of 30 Swiss- ICR mice, 14 animals developed benign skin tumors and 3 animals had carcinomas. In a parallel assay of MS from the same cigarettes, a 50 percent CSC:acetone suspension applied to deliver a comparable dose of CSC to 100 Swiss-ICR female mice led to benign skin tumors in 24 mice and to malignant skin tumors in 6 mice. This indicates that this smoke condensate of SS had greater tumorigenicity on mouse skin than MS tar (p >0.05). In Vitro Assays Several short-term bioassays have been performed to evaluate the genotoxicity of the MS of cigarettes. These studies have been the subject of two reviews (DeMarini 1983; Obe et al. 1984). Although most of these studies have evaluated the effects of CSC, some investigations were focused on either the gas phase or the whole smoke. In recent years, there has been increased use of short-term assays to attempt to evaluate the relative genotoxic potential of environmental tobacco smoke. 250 cigarettes, metabolic activation was rea. demonstrate mute genic activity for most of the CSC studied. ° =e Several short-term tests have been rf in eukeryotic systems. A solution of the gas phase of mainstrean, cigarette mea dissolved in a phosphate buffer induced reciprocal mitotic recombi nation in Saccharomyces cerevisiae D3 and petite mutants in an isolate of strain D3 (Izard et al. 1980). Whole mainstream cigarette smoke induced mitotic Bene conversion, reverse mutation, and io mitotic recombination in strain D7 of S. cerevisiae (Gairola 1 . Transformation of mammalian cells was also induced in several cell systems using the CSC from mainstream Cigarette smoke (Lasnitzki 1968; Inui and Takayama 1971; Rhim and Huebner 1973; Benedict et al. 1975; Takayama et al. 1978; Rivedal and Sanner 1980). Transplacental exposure to mainstream CSC was reported to transform Syrian hamster foetal cells (Rasmussen et al. 1981). Transforming activity was reported in the acidic and basic fractions as well as the neutral fractions of CSC. Studies on subfractions of CSC have shown that the basic fraction and some of the acidic fractions are the most active in cell transformation (Benedict et al 1975). The neutral fraction of CSC was also reported to inhibit DNA repair in normal human lymphocytes (Gaudin et al. 1972). Transfor- mation of mammalian cells with SS or ETS has not been reported. Summary of Carcinogenicity At present, the scientific literature offers some information on the physicochemical nature of the sidestream smoke from tobacco products and of environmental tobacco smoke. Chemical analytical studies have already demonstrated that SS and ETS contain a wide spectrum of carcinogens such as polynuclear aromatic hydrocarbons, 251 volatile and tobacco-specific N-nitrosamines, and polonium-210. To date, only one study has demonstrated the carcinogenic activity of the particulate matter of sidestream smoke and a few isolated reports have dealt with the genotoxicity of SS and ETS. Therefore, bioassay studies with the mainstream smoke and the environmental tobacco smoke of cigarettes are needed. Although the resulting bioassay data will derive from tests of concentrations of environmen- tal smoke that do not realistically occur in the human setting, these results will provide information about the relative carcinogenic potential of sidestream smoke in comparison with the mainstream smoke of the same cigarettes. In a comprehensive analytical approach, data should be generated to systematically determine the concentrations of toxic and tumorigenic agents in the ETS samples and to simultaneously measure the uptake of tobacco-specific agents by the body fluids of nonsmokers exposed to ETS. Conclusions 1. The main effects of the irritants present in ETS occur in the conjunctiva of the eyes and the mucous membranes of the nose, throat, and lower respiratory tract. These irritant effects are a frequent cause of complaints about poor air quality due to environmental tobacco smoke. 2. Active cigarette smoking is associated with prominent changes in the number, type, and function of respiratory epithelial and inflammatory cells; the potential for environmental tobacco smoke exposure to produce similar changes should be investi- gated. 3. 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New York, Academic Press, 1967. 260 CHAPTER 6 POLICIES RESTRICTING SMOKING IN PUBLIC PLACES AND THE WORKPLACE CONTENTS Introduction Current Status of Restrictions on Smoking in Public Places — Legislative Approaches Federal Legislation State Legislation Local Legislation Regulatory Approaches Smoking Regulation in Specific Public Places Public Transportation Retail Stores Restaurants Hotels and Motels Schools Health Care Facilities Current Status of Smoking Regulations in the Workplace Smoking Policies Prevalence of Smoking Policies Reasons for Adopting Smoking Policies Barriers to Adopting Smoking Policies Types of Smoking Policies The “Individual Solution” Approach Environmental Alterations Restrictions on Employee Smoking Banning Smoking at the Workplace Preferential Hiring of Nonsmokers Implementation of Smoking Policies Impact of Policies Restricting Smoking in Public Places and in the Workplace Potential Impacts of Smoking Policies Policy Implementation and Approval Direct Effects: Air Quality and Smoking Behav- ior Indirect Effects: Knowledge, Attitudes, Social Norms, and Smoking Behavior Methodologic Considerations in Policy Evaluation 263 Study Design Assessing the Effects of Smoking Policies Review of Current Evidence on Impact Workplace Smoking Policies Policy Implementation Air Quality Policy Approval Smoking Behavior Attitudes About Smoking Management Issues Legislation Restricting Smoking in Public Places Policy Implementation and Enforcement Policy Approval Attitudes and Social Norms Smoking Behavior Recommendations for Future Research Conclusions Appendix: The Comprehensiveness Index of State Laws References 264 introduction workplace (Feldman et al. 1978; Eriksen, in Press; Walsh and Gordon 1986). Private sector initiatives have gained momentum in the 1980s. Businesses in a wide variety of industries have adopted smoking policies to protect employee health. Other private initiatives include no-smoking sections in restaurants, no-smoking rooms in hotels and motels, and smoking restrictions in hospitals. Though this trend was fueled by growing evidence about the health effects of involuntary smoking, it also reflects the changing public attitudes about smoking since 1964, when public attention was focused on the health hazards of cigarette smoking by the portation vehicles and motels, restaurants, stores, schools, health care facilities, and the workplace are addressed. The effects of smoking policies on air quality, attitudes, and smoking behavior are considered. Current Status of Restrictions on Smoking in Public Places Smoking regulations in public places represent a mix of public and private actions, A public place may be defined as any enclosed area in which the public is permitted or to which the public is invited. 265 and the methods by which new smoking restrictions have been proposed and adopted. Smoking in Federal, State, and local government facilities has been addressed by legislative and regulatory action. These facilities include government offices, public schools and libraries, and publicly owned transportation, health care, cultural, and sports facilities. In public facilities under private ownership, smoking restrictions are a mixture of government-sponsored regulation and private initiative. These facilities include retail stores, restaurants and bars, hotels and motels, and privately owned transportation, health care, cultural, and sports facilities. The extent and acceptability of smoking restrictions in public places is influenced by (1) whether ownership is public or private; (2) the historical acceptance of smoking in the facility; (3) the degree to which nonsmokers are exposed to involuntary smoking, determined by the facility’s size, degree of ventilation, and ease of separating smokers and nonsmokers; and (4) the degree of inconvenience that smoking restrictions pose to smokers. Smoking restrictions are still most widespread and least controversial in facilities where smoking has traditionally been prohibited by fire codes, such as theaters or libraries, or where smoking is negatively associated with the activity taking place, such as gyms or health care facilities (Feldman et al. 1978). Small crowded areas with poor ventilation, such as elevators and public transit vehicles, are also frequently regulated. On the other hand, the strong association of smoking with eating and drinking contributes to the controversial nature of smoking restric- tions in restaurants and bars. Legislative Approaches Federal Legislation Congress has enacted no Federal legislation restricting smoking in public places, although bills have been introduced in Congress several times since 1973 (Feldman et al. 1978). State Legislation Most legislation restricting smoking has been enacted at the State level. Although legislation regulating smoking for health reasons is largely a phenomenon of the past decade, cigarette smoking has been the subject of restrictive legislation for nearly a century. Early legislation had two different rationales. The first, a relatively noncontroversial rationale, was the protection of the public from fire or other safety hazards, largely in the workplace (Warner 1981b). The second, more controversial motivation for early legislative action was a moral crusade against cigarettes similar in tone and coincident with the moral crusade against alcohol that emerged at 266 enforcing the regulations Proved controversial. As part of the strong reaction to alcohol prohibition, all State laws banning smoking were repealed by 1927. In the early 1970s, a new wave of smoking legislation emerged. It covered smoking in a larger number of Places and extended for the first time to privately owned facilities. The language became more Annual 1985). It covered restaurants, private worksites, and a large number of public places, and soon became the model for other State legislation. Within the next 5 years, Utah, Montana, and Nebraska enacted similar comprehensive legislation (US DHHS 1985b). The 267 45 - || Extensive 40 Moderate Basic Nominal 35 30 25 15 & Number of States with laws in effect 10 & Yj | FIGURE 1.—Prevalence and restrictiveness of State laws regulating smoking in public places, 1960-1985 NOTE: See appendix for definitions of reatrictiveness of laws. SOURCE: ASH (1986); OTA (1986); Tri-Agency Tobacco Free Project (1986); US DHHS (1985b). The rate of enactment of State legislation increased throughout the seventies (Figure 1, Table 1). The pace of new legislation continues in the 1980s, with 23 new laws enacted by 16 States between 1980 and 1985 (Table 1). As of 1986, 41 States and the District of Columbia have enacted laws regulating smoking in at least one public place (Figure 1). Eighty percent of the US. population currently resides in States with some smoking restric- tion, compared with 8 percent in 1971 (Warner 1981b). Most of the nine States with no smoking legislation are concentrated in the southeast United States and include three of the six major tobacco- producing States (North Carolina, Virginia, and Tennessee) (Figure 2). Current State legislation varies in comprehensiveness and lan- guage. The number of public places in which smoking is regulated by State law ranges from 1 (Delaware, Mississippi, and South Carolina regulate smoking on public transportation only) to 16 (Minnesota and Florida) (US DHHS 1985b, Tri-Agency Tobacco Free Project 268 TABLE 1.—State laws restricting smoking, 1970-1985 Number of Cumulative number newly enacted of States with _Reatrictiveneas of Average Year laws laws in effect newly enacted laws! of laws in effect 1892-1969 - 14 ~ 250 1970 0 i ~ 250 1971 2 16 250 20 1972 1 WW 20 20 1973 3 2 30 383 1974 3 22 ALT 296 1975 12 27 419 339 1976 5 30 563 425 1977 6 33 542 462 1978 2 34 625 478 1979 4 37 688 507 1980 1 a7 - ‘or 1981 6 39 500 513 1982 1 39 - on 1983 4 40 688 538 1984 3 41 ‘867 548 — 8 42 m9 619 ‘ Index of Restrictivenessa O = None; no statewide restrictions. 0.25 = Nominal; State regulates smoking in one to three public places, excluding restaurants and private worksites. 0.50 = Basic; State regulates smoking in four or more Public places, excluding restaurants and Private worksites. 0.75 = Moderate; State regulates smoking in restaurants but not Private worksites, 1.00 = Extensive; State regulates smoking in private worksites. * New California laws in 1980 and 1982 extended smoking restrictions to additional public places, but did not alter the restrictiveness of the State law (moderate). / 1986). State laws most often restrict smoking in public transporta- tion (85 States), hospitals (33 States), elevators (31 States), indoor cultural or recreational facilities (29 States), schools (27 States), public meeting rooms (21 States), and libraries (19 States) (Table 2). Other public places specifically mentioned in State smoking legisla- tion are public restrooms and waiting rooms, jury rooms, polling places, prisons, hallways, stairwells, and stables. Most laws restrict smoking in these places to designated areas, thereby making nonsmoking the norm; in a few States smoking is banned entirely in these places. For example, smoking on public transportation is banned entirely in four States (Florida, Georgia, Massachusetts, and Washington) and one (Washington) bans smoking in theaters, museums, auditoriums, and indoor sports arenas. Smoking restric- 269 a) ay Uy WB Extensive . — EE] Moderate & Basic Nominal (C) No restrictions FIGURE 2.—Geographic variability of State laws regulating smoking in public places, 1986 NOTE: See appendix for definitions of restrictiveness of laws. SOURCE: ASH (1986); OTA (1986), Tri-Agency Tobacco Free Project (1986); US DHHS (1985b). tions extend to restaurants and retail stores, which are largely privately owned, in 18 States. Smoking at the workplace is restricted for public sector employees in 22 States and for private sector employees in 9 States. The provisions of worksite smoking legislation vary widely, making direct comparisons of their comprehensiveness difficult. Currently enacted workplace smoking laws contain provisions to (1) require a written policy (5 States); (2) limit smoking to designated areas (8 States); (3) require the posting of signs (10 States); and (4) give preference to nonsmokers in resolving conflicts over the designation of a work area (2 States) (OTA 1986). Public or private worksites are included in the definition of public places in some States where worksites are subject to the general provisions for public places. Other States have written separate guidelines for the worksite, which are usually more stringent. Laws in four States apply only to State and local government employees; restrictions apply to the private worksite in an additional nine States. 270 TLE State AL AK AZ AR CA co CT DE pC FL GA HI ID IL_ IN IA KS KY 1971,76 1973 1925 Year(s) legislation 1975 1973 1977 1980,81 1977 1974 1983 1975 enacted — 1984 1981 1985 1982 1985' 1983 1960 1979 1985 1975 1976 1985 — 1978 1975 1972 PUBLIC PLACES WHERE SMOKING IS PROHIBITED (EXCEPT IN DESIGNATED AREAS) Public transportation xX xX (X)? X34 x x: x xX X35 xX® xX xX xX X Elevators xs xX xX xX* xX xs x* x xX xX xX Indoor recreational or cultural facilities * X xX xX xX xX xX xX xX x Retail stores (X)" (X)? xX xX xX xX xX Restaurants x* x? X x" X* xX Schools x x xX xX xX xX xX xX xX x Health care facilities Hospitals x x x xX xX x X xX x xX xX xX Nursing homes xX x Xx x x X Xx x X Public meeting rooms xX xX x xX xX x xX xX x Libraries x xX x xX x Restrooms xs x xX xX xX Waiting rooms xX X xX xX xX »« Other X27 X27 X26.27.30 WORKSITE SMOKING RESTRICTIONS ** Public worksites Dp" B D! B B B,D‘? B! B D Private worksites A B B,D IMPLEMENTATION PROVISIONS Nonsmokers prevail in disputes x No discrimination against nonsmokers ENFORCEMENT Penalties for violations xX x xX xX x xX xX xX xX X xX x x xX Smoking X23 X23p X2e X2e X23 X23 X23e X23 X23e X23 X2ad X23 Z23 X230 Failure to post signs XMh Kh Overall State law restrictiveness: ** 0 3 2 1 3 3 4 1 2 4 1 2 3 0 0 2 2 1 Glo TABLE 2.—Continued State LA ME MD MA MI MN MS MO MT NE NV NH NJ NM NY NC ND OH 1954 1924 =. 1967 1955 1921 Year(s) legislation 1981,83 1957 1947-1968 = 1971 1911 1979 1975 1981 enacted - 1985 1975 «61975 1978 1975 1942 — 1979 1979 1975 1981 1985 1985 1976 — 1977 1984 PUBLIC PLACES WHERE SMOKING JS PROHIBITED (EXCEPT IN DESIGNATED AREAS) Public transportation x xé (Xx)? x x x x x x x x x x x Elevators Xx xs x x x x x x x x x x Indoor recreational or cultural facilities * xX x x x x x x x x x Retail stores x )" xX x xX x xX x Restaurants xX x" xX xX x" x" x Schools x xX x x x x x x x Health care facilities Hospitals x x x x x x xX x x x x xX x Nursing homes xX x xX x x x xX x xX xX x x x Public meeting rooms x x xX x x x x x x Libraries x x xX Xx x x x x Restrooms x x x x x Waiting rooms x x x x x x x Other x 50 x 48 X%27 xX av xX a x 2s WORKSITE SMOKING. RESTRICTIONS '* Public worksites BD Dp" p D" p* BC" BC c c Private worksites B,D p72 pb” pial As Bc” A™ IMPLEMENTATION PROVISIONS Nonsmokers prevail . in disputes x xX No discrimination against nonsmokers x ENFORCEMENT ELS State OK OR PA he sc SD TN TX UT VT VA WA WV WI WY 1973,75 1927 1913 Total Year(s) legislation 1977 1947 1976 1976 1919 N (%) enacted 1975 1981 1977 1977 1997 1974 — 1975 1979 1892 — 1983 1985 1984 — 51 (100) PUBLIC PLACES WHER SMOKING IS PROHIBITED (EXCEPT IN DESIGNATED AREAS) Public transportation xX x (Xx)? xX xX xX xs xX xX 35 (68.6) Elevators xX xX xX xX xX xX x* xX 31 (60.8) Indoor recreational or cultural facilities * xX x xX x x xX xX x® xX 29 (59.6) Retail stores xX xX xX xX x* xX 18 (35.3) Restaurants xX xX Xx x x 18 (35.3) Schools xX xX xX xX xX x® xX x 27 (52.9) Health care facilities Hospitals xX xX xX xX xX xX xX x 33 (64.7) Nursing homes xX xX x x x x x 29 (56.9) Public meeting rooms xX xX xs 21 (41.2) Libraries xX xX xX xX xX xX 19 (37.2) Restrooms X 11 (21.6) Waiting rooms xX X x 16 (31.4) Other xs x7 x's 12 (23.5) WORKSITE SMOKING RESTRICTIONS "° Public worksites D D" D D'* 22 (43.1) Private worksites Dizzz A D A” 9 (17.6) IMPLEMENTATION PROVISIONS Nonsmokers prevail in disputes xX 4 (78) No discrimination against nonsmokers x 2 (3.9) ENFORCEMENT Penalties for violations X xX xX xX x x x X xX xX Xx 40 (78.4) Smoking X23 X23b X2ie X23 X23p X230 X230 X23a X25f 0 X23e X2% 39 (76.5) Failure to post signs X24e Xz Xzc 9 (17.6) Overall State law restrictiveness: *® 2 3 2 3 1 2 0 2 4 1 0 4 1 3 0 a op TABLE 2.—Continued (Footnotes) ‘ Executive order. 1 School buses only. ‘Including school buses. * California stipulates that at least 50 percent of all passenger seats must be in nonsmoking areas on trains, airplanes, and street railroad cars departing from the State. * Smoking never permitted in this area. “Indoor recreational and cultural facilities: museums, auditoriums, theaters, and sports arenas. 7 Grocery stores only. * Restaurants seating 50 or more persons must have a no-smoking section. * Restaurants seating 50 or more persons must have a no-smoking section if the restaurant is in a publicly owned building. ‘© Restaurants seating 75 or more persons must have a no-smoking section. » Restaurants must designate at least 30 percent of their seats as a no-smoking area. '? Restaurants are encouraged to establish no-smoking areas. ‘3 Restaurants must designate at least 50 percent of their seats as a no-smoking area. '«(Deleted). ‘* No place other than a bar may be designated a smoking area in its entirety. ‘* Worksite (only B, C, and D count as having a worksite policy in caculation of totals): A - Employer must post a sign prohibiting smoking at the worksite; B ~ Employer must have a (written) smoking policy; C - Employer must have policy that provides a nonsmoking area; D - No smoking except in designated areas. 11 Employer must post signs designating smoking and no-smoking areas. 18 Employer must post signs in smoking areas. 1* Employer must post either smoking or no-smoking signs, depending upon their policy. *° Employer must post signs in no-smoking areas. *1 State does not restrict smoking in factories, warehouses, and similar places of work not usually frequented by the general public. 1 Prohibits smoking in any mill or factory in which a no-smoking sign is posted. *3 Persons who smoke in a prohibited area are subject to a fine or a penalty. Maximum fines or penalties, where applicable, are listed below: a = $5; b = $10; c = $25; d = $50; e = $100, f = $100/day; g = $200; h = $300; i = $500; j = $50 or up to 10 days in jail or both; k = $50 or 90 days imprisonment; | = civil action; m = minor misdemeanor; n = petty misdemeanor; 0 = misdemeanor; p = petty offense. * Persons who are required to and fail to post smoking and/or no-smoking signs are subjected to a penalty. Maximum fines, where applicable, are listed in footnote 23. *6 Reatrictiveness key: 0 = None, no statewide restrictions; 1 = Nominal, State regulates smoking in one to three public places, excluding restaurants and private worksites; 2 = Basic, State regulates smoking in four or more public places, excluding restaurants and private worksites, 3 = Moderate, State regulates smoking in restaurants but not private worksites; 4 = Extensive, State regulates smoking in private worksites. ** Jury rooms. #7 Halls and stairs. ™* Stables. »* Polling places. 9° Prisons, at prison officials’ discretion. The least restrictive workplace laws simply empower the employer to restrict smoking in factories by posting signs. These statutes were enacted in the early 1900s. The weakest recent laws simply require an employer to issue a written smoking policy and to post signs. More restrictive laws require that employers designate no-smoking areas at work, implying that smoking is the norm. The most comprehensive laws prohibit smoking except in designated areas, making nonsmoking the norm. Seven States (Florida, Maine, Minne- sota, Montana, Nebraska, Utah, and Washington) have this type of law. In several States, some worksites or some parts of a worksite {usually private offices) are exempted from the regulations. To prevent employers from complying with the letter but not the intent of the law, some States prohibit a workplace from being designated as entirely smoking. State laws vary in their provisions for implementation and enforcement. In most States, the State health department is responsible for policy enforcement. Nearly all (39 of 42) States with laws provide penalties for smokers who violate restrictions; the maximum penalty is $500. In two States violators can be jailed. Employers or others who fail to designate smoking areas can be fined in nine States. The comprehensiveness of State laws, as defined by the number and nature of places where smoking is restricted or prohibited, has increased since 1970. In 1981, Warner (1981b) classified State laws according to their comprehensiveness (restrictiveness) and docu- mented an increase in the average restrictiveness from 1971 to 1978. An updated and modified index of the comprehensiveness of State laws (described in the appendix) demonstrates that the phenomenon reported by Warner has continued into the mid-eighties. The comprehensiveness of newly enacted laws increased markedly dur- ing the mid-seventies, and the average restrictiveness of State laws in effect has increased more than twofold between 1972 and 1985 (Table 1, Figure 3). As shown in Figure 1 and Table 1, the increase in comprehensiveness of State laws occurred in two ways. The average comprehensiveness of first laws in additional States increased, and existing State smoking laws were replaced with more comprehensive legislation. Warner also documented that both the prevalence and comprehen- siveness of State laws enacted through 1978 varied by geographic region (Warner 1982). This has not changed (Table 3, Figure 2). Over 90 percent of the States in the Northeast and West have enacted at least one law regulating smoking, as have three-fourths of the North Central States. Southern States have fewer laws than other regions, and the laws they have are less comprehensive than laws in other ‘regions. The six major tobacco-producing States, all located in the South, have less restrictive laws than do the other six Southern 275 0.65 0.60 -— 0.55 0.50 0.45 p= 0.40 Average restrictiveness of laws in effect 0.35 0.30 0.25 L. L { [ee Ge ee | jj if { fo jf td 1960 1965 1970 1975 1980 1985 Year FIGURE 3.—Average restrictiveness of State laws in effect, 1960-1985 NOTE: Coding of restrictiveneas of law; Extensive = 1.00, Moderate = 0.75; Basic = 0.50; Nominal = 0.25. (See appendix for definitions of restrictiveness of laws.) SOURCE: ASH (1986), OTA (1986); Tri-Agency Tobacco Free Project (1986); US DHHS (1985b). States. Compared with other States, major tobacco States are less likely to have enacted smoking legislation and more likely to have enacted less stringent laws. 276 TABLE 3.—Regional variation in State laws restricting smoking Total States Average Statea with laws’ Average restrictiveness _— effective date of laws in effect Region N N (%) of first law in 198523 Northeast 11 11 — (100) 1944 614 North Central 12 9 (75) 1976 694 West 15 14 (93) 1968 714 South 12 7 (58) 1955 357 Major tobacco- producing States * 6 3 (50) 1961 250 Other southern States 6 4 (67) 1951 438 ‘Differences in prevalence of laws among four regions: chi square; (3 df) = 8.67, p = 0.03; difference in prevalence of laws, South vs. all others: chi square (1 df) = 5.99, p = 0.04. ? Includes only States with laws in effect (see Table 1 for Index of Restrictiveness). 3 Difference in restrictiveness, South vs. all others: t = 2.76, p = 0.03. “North Carolina, South Carolina, Virginia, Kentucky, Tennessee, Georgia. Local Legislation In the 1980s, the momentum of nonsmokers’ rights legislation spread from the State to the local level, spearheaded by actions in California (Warner et al. 1986). Although not the first local action, the successful passage of San Francisco’s Proposition P in 1983 in spite of heavily subsidized tobacco industry opposition attracted widespread publicity and was followed by the passage of comprehen- sive legislation in a number of other local communities (Doyle 1984). Many local ordinances extend existing State policies to restau- rants and worksites. According to a March 1986 survey, 74 Califor- nia cities and counties have passed smoking ordinances, including 62 requiring no-smoking sections in restaurants and 54 restricting smoking in retail stores (Americans for Nonsmokers’ Rights Founda- tion 1986). In the survey, 66 of these cities and counties require private employers to have a smoking policy or to identify no-smoking areas. As a result, 44 percent of California’s population lives in communities that have enacted workplace smoking ordinances even though California has no State legislation covering the private workplace. . According to the Tobacco Institute, by the end of 1985, 89 cities and counties nationwide had restricted smoking in the private workplace. As stated above, three-fourths of these were in California (BNA 1986). Workplace smoking ordinances have also been passed in Cincinnati (Ohio), Kansas City (Missouri), Tucson (Arizona), Aspen 277 (Colorado), San Antonio, Austin, and Fort Worth (Texas), Newton (Massachusetts), and Suffolk County (New York). In New York City, a bill to prohibit smoking in all enclosed public places has been proposed by the mayor (New York Times 7/6/86). Regulatory Approaches Administrative agencies have become involved in smoking regula- tion in two ways: (1) the enforcement of smoking legislation enacted by State and local government is commonly delegated to a specific agency, usually the public health department; or (2) an agency may initiate smoking regulation as part of the activities it has been authorized to supervise (Feldman et al. 1978). Agency regulations have been the major mode of regulation at the Federal level, where smoking by Government employees and by passengers in interstate transportation vehicles have been addressed. Smoking by State and local employees has also been addressed by the actions of administra- tors; e.g., smoking by municipal employees and in public areas of municipal buildings was banned by a recent mayoral order in New York City (New York Times 6/26/86). Smoking Regulation in Specific Public Places Public Transportation Because high concentrations of environmental tobacco smoke can accumulate inside public transport vehicles, smoking is often restricted or banned in public transportation. Smoking is likely to be banned entirely in vehicles where smokers spend relatively little time (e.g., city buses), and confined to designated areas in situations where smokers spend several hours (e.g., intercity buses, trains, and airplanes). Such restrictions are relatively well accepted. Smoking on interstate transportation vehicles is regulated by Federal agencies. The Civil Aeronautics Board, under its jurisdiction to “ensure safe and adequate service, equipment, and facilities,” initially regulated smoking on airplanes, requiring, since 1972, that every commercial air flight provide a no-smoking section for all passengers requesting such seating (Feldman et al. 1978; Walsh and Gordon 1986). Airline control is currently part of the authority of the U.S. Department of Transportation. Likewise, the Interstate Com- merce Commission has restricted smoking on buses and trains to designated areas since the early 1970s (Feldman et al. 1978; Walsh 1984). Additionally, States and local governments have regulated smok- ing in public transportation vehicles. Thirty-one States have enacted legislation to restrict smoking to designated areas in public transit vehicles; an additional four (Florida, Georgia, Massachusetts, and 278 Washington) ban smoking entirely on these vehicles (Table 2). Local ordinances also frequently address public transportation. Retail Stores In general, State and local legislation prohibiting smoking in retail stores is well accepted. Eighteen States currently prohibit smoking in retail stores (Table 2). Proprietors and their trade associations have generally supported smoking restrictions out of concern for the costs of cigarette burns to merchandise and facilities and for the image presented to customers by employees. Furthermore, their business is less likely to be affected than, for instance, the restaurant trade because smoking is not as closely associated with shopping as it is with eating and drinking. Restaurants The average American, who according to National Restaurant Association (NRA) statistics eats out 3.7 times per week, has the potential for repeated environmental tobacco smoke (ETS) exposure (NRA 1986). This is a problem particularly in small restaurants, where ventilation may not be able to remove smoke and room size precludes a meaningful separation of smokers and nonsmokers. Public opinion polls document support for restaurant smoking restrictions among nonsmokers and smokers. Ninety-one percent of nonsmokers and 86 percent of smokers responding to a 1983 Gallup poll favored either restricting or banning restaurant smoking, with most preferring restriction (Gallup 1983). Similar results were reported by two regional polls in 1984 (UC SRC 1984, Hollander- Cohen Associates 1984). Roper polls in 1976 and 1978 demonstrated the growth in this sentiment during the mid-seventies; the propor- tion of respondents supporting restrictions grew from 57 percent to 73 percent in 2 years (Roper 1978). Yet little is known about how restrictions affect decisions to dine out or the choice of restaurant. A 1981 telephone survey of 949 individuals conducted by the NRA (1982) found that the existence of a no-smoking section was near the bottom of a list of 13 attributes influencing an individual’s choice of restaurant. On the other hand, 47 percent of 1,038 adults answering a 1984 Gallup Monthly Report on Eating Out stated that one reason they did not eat out more was that they were bothered by smoke (Gallup 1984). As in other privately owned facilities, smoking regulations in restaurants have come about through private initiative and public mandate. Private initiatives have sometimes occurred in anticipa- tion of a local ordinance, but the number of restaurants that have voluntarily established no-smoking sections is not known. The 279 Ontario Restaurant and Food Services Association (1985) published a handbook of guidelines for establishing no-smoking sections. In 1974, Connecticut became the first State to require restaurants to have no-smoking sections. By 1980, eight other States also regulated restaurant smoking. At present, laws in 18 States and an unknown number of localities regulate smoking in restaurants. Although a nationwide accounting of local regulations is not available, data are available for several States (Table 2). Most State and local ordinances specify (1) the minimum number of seats that must be included in a no-smoking section, (2) the smallest restaurant for which rules apply, and (3) the manner in which customers are to be informed about no-smoking sections. Bars that do not serve meals are uniformly excluded from restrictions. Most current State legisla- tion specifies that a minimum of 30 percent of seats be designated as no-smoking and exempts facilities with fewer than 50 seats. Local ordinances are generally more restrictive, specifying that a higher percentage of seats be designated no-smoking and extending cover- age to smaller establishments. Model ordinances (Hanauer et al. 1986) suggest that a minimum of 50 percent of seats be designated as no-smoking, require the posting of signs inside and outside the facility, and specify that owners ask patrons about smoking prefer- ence rather than respond only to customer requests. There has been more opposition to smoking restrictions in restaurants than in other privately owned public places (Hanauer et al. 1986). Opposition has come primarily from restaurant associa- tions and centers on three concerns: (1) government intrusion into business practice, (2) practical problems in coordinating seating of smokers and nonsmokers, and (3) losing the business of smokers who chose to leave a facility rather than to dine in a no-smoking section or wait for an available table in a smoking section. These concerns assume that the supply of no-smoking tables will exceed demand. While the proportion of tables allocated by most laws to no-smoking sections greatly underrepresents the proportion of nonsmokers, mixed parties of smokers and nonsmokers would have to decide which section to sit in. Restaurant owners appear to perceive little customer demand for no-smoking areas, or are unaware of the very high percentage of smokers and nonsmokers responding to public opinion polls who support smoking restrictions. In anecdotal reports, the experience of restaurant owners who have implemented restrictions is that they are well accepted by customers and less difficult to implement than expected (Lehman 1984). There is little information on the extent of restaurant compliance with State and local laws. In Park City, Utah, the Chamber of Commerce polled its 32 member restaurants, and only 25 percent had complied with State law to set up no-smoking areas (Park Record 6/13/85). However, a random survey of Minneapolis 280 restaurants in 1976, 1 year after enactment of the comprehensive Minnesota Clean Indoor Air Act, found near-total compliance with the State’s smoking regulations (Sandell 1984). In a 1978 Minnesota survey, 66 percent of nonsmokers and 81 percent of smokers felt that there were adequate no-smoking areas in that State’s restaurants (Minneapolis Tribune 1978). Hotels and Motels Over the past decade, hotel and motel operators have begun to offer guest rooms in which smoking is prohibited. In some facilities, no-smoking areas in lobbies and restaurants are also provided. Hotels are unique among public places in the manner and ease with which smoking has been addressed. Unlike the situation in restau- rants, among hotels the no-smoking room policy is uniformly a private initiative, introduced by management in response to per- ceived customer demand (Linnell 1986). Hotel and motel rooms are not covered by State and local regulations and have not been addressed by nonsmokers’ rights advocates. Designating guestrooms as no-smoking began in the early 1970s in smaller hotel and motel chains. In the 1980s, the concept has spread to larger chains, including Hyatt Hotels in 1984 and Hilton Hotels in 1986 (Los Angeles Times 1986). According to a 1985 survey of 98 hotel and motel chains, 37 of 41 respondents provided no-smoking rooms, 23 by chainwide policy. The four respondents who did not offer no-smoking rooms were considering doing so (Linnell 1986). The percentage of rooms allocated as no-smoking varied from 5 to 30 percent, far less than the prevalence of nonsmokers in the adult population (70 percent). As a result, demand often exceeds supply, leading several chains to increase the percentage of no-smoking rooms (Linnell 1986; Vettel 1986). The only entirely no-smoking facility is the Non-Smokers Inn, a 134-room motel in Dallas, Texas, which has been open since 1982 and reports a 96 percent occupancy rate (Vettel 1986). Although there are anecdotal reports of problems with compliance, hotels do not have penalties for violators. The exception is the Non-Smokers Inn, where at check-in guests sign an agreement to abide by the rule; if the management detects smoking by occupants, $250 is charged to cover the costs of cleaning. Whether no-smoking guestrooms offer significant protection from sidestream smoke exposure is not clear. It is not known whether nonsmokers are exposed to significant quantities of ETS by staying in hotel rooms previously, but not currently, occupied by smokers. Rooms designated as no-smoking may primarily allow nonsmokers to avoid stale tobacco odors. The regulation of smoking in hotels and motels is supported by public opinion. Fifty to sixty percent of respondents to recent opinion polls favor restrictions on smoking in hotel rooms, and an additional 281 7 to 18 percent favor outright bans on smoking (Gallup 1983, UC SRC 1984, Hollander-Cohen Associates 1984). In the 1983 Gallup poll, 60 percent of nonsmokers and 49 percent of smokers supported smoking restrictions in hoiels, with an additional 15 percent of smokers and 7 percent of nonsmokers favoring outright smoking bans. Hotel management regards such policy as a marketing tool. Cost savings do not appear to be a motivating force in the trend, in spite of anecdotal reports of reduced cleaning and maintenance costs in no-smoking rooms (Linnell 1986). Preparing no-smoking rooms requires an up-front cost for the thorough cleaning of furnishings and often the repainting of walls. For instance, Quality Inns estimated that it spent $138 per room when it allocated 10 percent of its rooms as no-smoking in 1984 (Vettel 1986). Schools Smoking by students in schools has been the subject of State legislation, State and local school board regulations, and individual school policies. Colleges and universities are not discussed in this section. In 27 States, schools are among the public places where smoking is restricted to designated areas (Table 2). School board policies often combine restrictions on tobacco use in schools with educational programs about the hazards of tobacco use. Smoking by teachers, for whom school is the workplace, is also regulated by many school boards. Smoking has traditionally been regulated in schools for reasons other than concern about sidestream smoke exposure. The two rationales have been to comply with State law and to prevent the initiation of smoking by adolescents. The sale or use of tobacco by minors is prohibited in 35 States (Breslow 1982). Many of these laws are rendered ineffective by the availability of cigarettes in vending machines and by cultural norms that discourage the laws’ enforce- ment (US DHEW 1969). Nonetheless, the laws do provide a legal incentive for schools to regulate student smoking. The second reason for restricting smoking in schools is that adolescents are making decisions about whether to begin smoking and the influence of peers as well as of adult role models who smoke is recognized to be important (US DHHS 1980, 1982). Recognition of the health effects of involuntary smoking provides an additional reason to address smoking in schools and a reason to expand attention from students to faculty. For teachers and staff, the school is the worksite, a location with the potential for substantial ETS exposure (Repace and Lowrey 1985). For students, school is the site where they spend the most time outside of the home. 282 A total prohibition of smoking on school grounds provides the greatest protection from sidestream smoke exposure and unwanted role modeling effects. In practice, however, this policy has often proved difficult to enforce effectively (Rashak et al. 1986). In some cases it has created major discipline problems and required substan- tial time and personnel for enforcement. School officials, faced with the management of other social problems, may not wish to devote much of their resources to enforcement of a strict smoking ban. Consequently, many schools have established student smoking areas inside or outside the school building. Use of these areas often requires parental permission. Smoking areas for students are not popular with parents or teachers, according to survey data. Over three-fourths of 603 adults responding to a 1977 Minnesota poll opposed allowing school boards to establish smoking areas for students. Only 13 percent of 1,577 public school teachers responding to a 1976 nationwide survey thought students should be able to smoke on school grounds. The nature and extent of school smoking policies nationwide is not known. Results of the few statewide surveys vary considerably. A Connecticut survey reported that 75 percent of the State’s public high schools permitted smoking (Bailey 1983). In contrast, in Arizona, where State law requires schools to restrict smoking on school grounds, 92 percent of the State’s 169 public and private secondary schools surveyed had written smoking policies for stu- dents, and most policies prohibited all tobacco use by students (Rashak et al. 1986). Smoking by teachers at schools is generally prohibited in the classroom, but is often permitted in a lounge where students are not allowed. Ninety percent of Arizona schools permit smoking in teachers’ lounges, 40 percent in private offices, and 19 percent in meetings (Rashak et al. 1986). Such policies attempt to avoid negative role modeling effects; however, they create a double standard that may be a barrier to student compliance with smoking bans. There has been little concern for protecting teachers from involuntary smoke exposure at the worksite. Since smoking is prohibited in the classroom, their exposure is limited to offices and lounges. Health Care Facilities There are strong reasons for health care facilities to have particularly stringent restrictions on smoking. Many patients treat- ed in these facilities suffer from illnesses whose symptoms can be worsened by acute exposure to tobacco smoke. Hospitals also convey messages about health to patients and visitors; permitting smoking on the premises may undermine the messages delivered to many patients about the importance of not smoking (Kottke et al. 1986). 283 Stringent restrictions on smoking in hospitals have been endorsed by the American Academy of Pediatrics (1986), the American Medical Association (1984), and the American College of Physicians (1986). Hospital smoking policies have been opposed by some who are concerned about inconveniencing smokers at times of illness and stress. Proponents of hospital no-smoking policies, on the other hand, are concerned about inconveniencing the nonsmoking patient or visitor at these stressful times. Public opinion supports smoking restrictions in health care facilities. In the 1978 Roper survey, 69 percent of respondents favored a ban on smoking in doctors’ and dentists’ offices and waiting rooms (AMA 1984). Of the more than 3,000 individuals interviewed in hospitals and restaurants, 66 percent favored restric- ting or banning smoking in these areas (Barr and Lambert 1982). Over 80 percent of patients and faculty and 68 percent of employees agreed that “a smoke-free hospital would be an improvement in patient care” at the University of : innesota hospital (Kottke et al. 1986). Smoking in health care facilities has been addressed through State and local legislation, Federal regulation, and private initiative. In most States, hospitals and nursing homes are included among public places where smoking is restricted to designated areas (Table 2). In many cases, these legislative efforts have not led to strong protection of patients from involuntary smoke exposure because patient care areas may be included among the designated areas where smoking is permitted. Federally run hospitals have adopted increasingly strin- gent restrictions on smoking. For instance, Veterans’ Administra- tion hospitals and clinics adopted a new smoking policy in 1986, and a large number of Indian Health Service hospitals are now entirely smoke free (OTA 1986; Rhoades and Fairbanks 1985). Health care facilities run by some States, such as Massachusetts, have also adopted no-smoking policies (Naimark 1986). In nongovernment hospitals, most smoking restriction has been the result of private initiative, often spearheaded by the medical staff. Much of this action has taken place in the 1980s. Hospital smoking policies can be complex. Within a single institution, smoking may be handled differently in inpatient, outpa- tient, and administrative areas. Patients, visitors, and empioyees may be subject to different sets of restrictions. Consequently, smoking policies vary widely among hospitals (Ernster and Wilner 1985). The least stringent policy prohibits smoking only where it is a safety hazard, such as near oxygen, and may permit the sale of cigarettes on the premises. Mild policies often assign patients to beds by smoking status, prohibit staff from smoking in patient care areas, and provide areas in cafeterias and waiting rooms for nonsmokers. Moderately stringent policies prohibit smoking in shared patient 284 rooms or in all patient rooms. Some hospitals permit patients to smoke with a doctor’s written order. The most stringent policies, the so-called smoke-free hospitals, prohibit smoking throughout the facility or limit smoking to a single room away from patient care areas (Kottke et al. 1986). Enforcement of a smoking policy is usually the responsibility of the nursing staff. Guidelines for implementing hospital smoking policies have been formulated (Kottke et al. 1986; Ernster and Wilner 1985; AHA 1982). In spite of anecdotal reports of the adoption of stringent smoking policies in individual hospitals (Andrews 1983), survey data indicate that smoking is still widely permitted in patient care areas. A survey of 360 randomly selected U.S. hospitals published in 1979 found few restrictions on smoking; fewer than half elicited the patients’ smoking preference on admission or had no-smoking areas in _ cafeterias, waiting rccms, or lobbies, and smoking was permitted on 76 percent of the wards (Kelly and Cohen 1979). A 1981 survey of 1,168 community hospitals (Jones 1981) documented some change in policy prevalence. More than 90 percent of the hospitals had a written smoking policy, which restricted smoking to designated areas in 97 percent of cases. Over 85 percent of the hospitals offered no-smoking patient rooms, subject to availability (Jones 1981). A recent survey of 185 hospital administrators in Georgia reported that 70 percent continue to allow smoking in patient rooms, although only 6 percent permit it at nurses’ stations (Berman et al. 1985). The proportion of hospitals allowing cigarette sales on the premises has declined from 56 to 58 percent in the late seventies (Kelly and Cohen 1979; Seffrin et al. 1978) to less than 30 percent in the eighties (Ernster and Wilner 1985; Jones 1981; Berman et al. 1985; Bertelsen and Stolberg 1981). While there are little data on the prevalence of smoking policies in private physicians’ offices, guide- lines for physicians wanting to provide assistance in smoking cessation are well developed (Lichtenstein and Danaher 1978; Shipley and Orleans 1982; US DHHS 1984). Current Status of Smoking Regulations in the Workplace Policies regulating smoking at the workplace for the protection of employees’ health are a trend of the 1980s. As of 1986, smoking is restricted or banned in 35 to 40 percent of private sector businesses (HRPC 1985; BNA 1986; US DHHS 1986) and in an increasing number of Federal, State, and local government offices (OTA 1986). Private sector workplace smoking is regulated by law in 9 States and over 70 communities (OTA 1986; US DHHS 1985b; ASH 1986). Actions to restrict or ban smoking at the workplace are supported by a large majority of both smokers and nonsmokers (Gallup 1985). 285 The workplace has become the focus of particular attention as evidence about the health hazards of involuntary smoking has accumulated. Urban adults spend more time at work than at any other location except home (Repace and Lowrey 1985). For adults living in a household where no one smokes (Haryis 1985), the workplace is the greatest source of ETS exposure. Consequently, an individual’s workplace ETS exposure can be substantial in duration and intensity. This is of particular concern for individuals also exposed to industrial toxins whose effects may be synergistic with tobacco smoke (US DHHS 1985c). Furthermore, individuals have less choice about their ETS exposure at work than they do in other places, such as restaurants or auditoriums. The nonsmoker’s right to clean air on the job has been supported by common law precedent (US DHHS 1985a; Walsh and Gordon 1986). Assuring clean air at work has received the growing attention of policymakers and nonsmokers’ rights advocates. The worksite has also received attention because of its naturally occurring interper- sonal networks and intrinsic social norms. Behavioral scientists have attempted to take advantage of the social milieu of the workplace to increase the success of smoking cessation programs (US DHHS 1985c). Smoking policies have the potential to alter worksite norms about smoking and thereby to contribute to reductions in employee smoking rates or the prevention of smoking onset. A substantial fraction of blue-collar workers who smoke report the initiation of smoking at ages coincident with their entry into the workforce (US DHHS 1985c). Smoking Policies Legislation mandating smoking policies in the private sector workplace has been more controversial and less widespread than legislation covering public places. Because a worker’s behavior off the job has traditionally been viewed as beyond the employer's legitimate concern, private employers have been reluctant to impose rules on behavior not directly related to employment (Walsh 1984; Fielding 1986). The concept of workplace smoking restriction has become more acceptable to employers and legislators as the hazards of involuntary smoking have become better known and as public attitudes about smoking have shifted. The rationale for policies has been reframed as guaranteeing an employee’s right to a healthy work environment. , Prevalence of Smoking Policies Notwithstanding the recent attention, regulating smoking at work is not a new idea. There is a long and noncontroversial tradition of smoking restrictions to insure the safety of the worker, workplace, and product (OTA 1986). Employers have restricted smoking to 286 prevent fires or explosions around flammable materials or to prevent product contamination. The policies were supported by State legisla- tion dating back to 1892, when Vermont authorized employers to ban smoking in factories so long as a sign was posted (Warner 1982; US DHHS 1985b). New York, Nevada, and West Virginia had enacted similar legislation by 1921, and in 1924 Massachusetts banned smoking in stables because of the fire hazard (US DHHS 1985b). Smoking restrictions remained uncommon throughout the 1960s. During the 1970s, workplace smoking regulations were included in the comprehensive clean indoor air legislation being proposed at the State level. In 1975, Minnesota became the first State to enact regulations for private worksites for the purpose of protecting employee health. Since then, eight other States have passed laws covering private sector workplace smoking (Tri-Agency Tobacco Free Project 1986; OTA 1986; ASH 1986; US DHHS 1985b). Fifteen percent of the U.S. population lives in these nine States. The scope of this legislative effort widened in the 1980s to include local govern- ment. It has been strongest in California, where ordinances in 66 communities cover 44 percent of the State’s population (Americans for Nonsmokers’ Rights Foundation 1986). In spite of this legislative activity, surveys of employers through the 1970s reveal that worksite smoking regulations remained limited overall (Table 4). Those in place applied primarily to blue-collar areas and were motivated by safety concerns (NICSH 1980a,b; Bennett and Levy 1980). Policies were more common in industries with product safety concerns (food, pharmaceuticals) or explosion hazards (chemicals) (HRPC 1985). Safety was the prime reason for smoking policies in a survey of 128 large Massachusetts employers in 1978-1979. The potential for an adverse impact on clients, especially in service industries, was also cited (Bennett and Levy 1980). Concerns about the impact of smoking on the health of employees or costs to employers—the focus of the current workplace smoking action—were not mentioned. Fewer than 1 percent of 855 employers answering a nationwide survey in 1979 had calculated the costs of employee smoking (NICSH 1980a,b). Five surveys of employers conducted between 1977 and 1980 document the situation just prior to the proliferation of workplace smoking policies. Estimates of the prevalence of smoking policies ranged from 14 to 64 percent, reflecting differences in types of businesses sampled and response rates (Table 4). A survey conducted by the National Interagency Council on Smoking and Health in 1979 had the largest sample size and the only random sample, but had a low response rate (29 percent) (NICSH 1980a). Their estimate of a 50 percent prevalence of smoking policies is probably biased upward by the likelihood that companies with policies were more likely to 287 882 TABLE 4.—Surveys of worksite smoking policies Worksite Incentives Business surveyed Interview Restrict cessation for Survey name Survey Sampling Response rate smoking program nonsmoking (pub. date) year Number Workforce size Location method Method Who? N (%) (%) (%) (%) Dartnell’s 1977 250 Large US. and ? Office ? 30 i 3 Business (1980) Canada administrators Bennett and 1978-79 128 Large Mass. All Mass. Mail 88 (66) 64 12 Levy (1980) (> 1000) business with > 1000 employees National Inter- 1979 3000 Three strata of 1000: US. Random sample Mail Top level 855 (29); same 50 15 1 agency Council small (50-499), medium stratified by and management for each strata on Smoking (500-2200), large size phone and health and Health (Fortune Double 500) officials (1980) Dartnell’s 1980 325 Large US. ? Administrative ? 23 9 3 Business (1980) managers Administrative 1980 500 7 U.S. and =Nonrandom, Mail Members of 302 (60) 14 Management Canada representatives AMS Society (Thomas of AMS 1980) chapters Human 1984-85 1100 Large: Fortune 1000 and USS. All members of Mail CEO or VP for 445 (40) 32 43 8.5 Resources Inc,’s 100 fastest growing two selected Human Policy Corp. companies groups Resources (1985) 686 TABLE 4.—Continued Worksite Incentives Business surveyed Interview Restrict cessation for Survey name Survey Sampling Response rate smoking program nonsmoking (pub. date) year Number Workforce size Location method Method Who? N (%) (%) (%) (%) U.S. Depart- 1985 1600 Two strata: small (50- US. Random sample Phone 1358 (85) 38 19 ment of Health 99), medium-large (> 100) stratified by and Human size, location, Services (1986) and industry type Bureau of 1986 1967 Predominantly small- US. Random Mail Personnel 662 (34) 36 41 4 National medium 80%-< 1000 sample, selected executives Affairs, Inc. group: Am. Soc. (1986) Pers. Admin. members Petersen and 1986 1100 Predominantly small- US., ? Mail ? 577 (53) 56 50 5 Massengil] medium: 62% - <500; Canada, (1986) 16% - 500-1000, 22% - and > 1000 Puerto Rico TABLE 4.—Continued Correlates of having a smoking policy Survey name Workplace Type of smoking policy Duration (pub. date) size Location Business type Other (B = ban, R = restrict Reason for policy of policy Comments Dartnell’s 42% <5 Employees Business (1980) years raised smoking issue in 25% Bennett and No No No No Protect products, Cigarettes Levy (1980) equipment (91%), sold on worker safety premises of (37%), customer 95% contact (17%), worker health (0%) National Inter- Large >small Bluecollar > Blue-collar areas 42%R/28%B, (<1% calculate 64% adopted Management- agency Council (54% vs 46%) white-collar white-collar areas 15%R/11%B, costa due to since 1964 initiated on Smoking and areas cafeterias 19%R/2%B, smoking policies with Health (1980) conference rooms 6%R/7%B, rare union medical facilities 15%R/25%B role; 54% with policies impoae penalties T6S TABLE 4.—Continued Correlates of having a smoking policy Survey name Workplace Type of smoking policy Duration (pub. date) size Location Business type Other (B = ban, R = restrict Reason for policy of policy Comments Dartnell’s 18% R to designated areas 69% <5 Employees Business (1980) (usually open offices and public years raised contact areas), 8% R in smoking issue cafeterias, 5% limit smoking to in 30%, 5% breaks more than in 1977 survey Administrative Office areas 12%R/2%B White-collar Management B: reception areas (46%), area survey Society (1980) security areas (35%), open only; 37% offices (27%), hallways (16%), without policy conference rooms (8%) had employee complaints 666 TABLE 4.—Continued Correlates of having a smoking policy Survey name Workplace Type of smoking policy Duration (pub. date) size Location Business type Other (B = ban, R = restrict Reason for policy of policy Comments Human West - 45%, >50%: Located 3% B while working or on Safety (25%), 51% <5 Sponsored by Resources Policy NE - 36%, insurance, where premises, 35% B by some health (20%), years Tobacco Corp. (1985) NC - 28%, pharmaceuticals, workplace employees, 5% do not hire comply with laws Institute; South - 22% finance, smoking law smokers (16%), employee management publishing; in effect preference (16%) initiated <20%: mining, save money (3%), policies; 70% consumer goods increase encourage productivity (2%) employees to Reasons reject settle own policy: disputes unacceptable to employees, employees settle own problem, implementation too difficult US. Depart- Large >small Services > Not unionized Comply with regs Data analysis ment of Health other industry or blue-collar (39%), protect still in and Human types % nonsmokers (39%), progress Services (1986) protect equipment (14%), protect high risk employees (8%) £66 TABLE 4.—Continued Correlates of having a smoking policy Survey name Workplace Type of smoking policy Duration (pub. date) size Location Business type Other (B = ban, R = restrict Reason for policy of policy Commer Bureau of Large >small West - 52%, Nonbusiness or Located Open work areas 19%R/41%B; Comply with laws 85% <5 2% to adopt National (45% vs 33%) EN - 42%, nonmanufacturing where halls, conference rooms, (28%), employee years 85%; policy in Affairs, Inc. NC - 29%, >manufacturing workplace restrooms, customer areas 56%- health, comfort 10% before 1986; 21% (1986) South - 28% smoking law 66%B; cafeterias 58% partial (22%), employee 1982 considering in effect B; total worksite 2%B; 1% hire complaints (21%), policy; 23% only nonsmokers, 5% prefer mandate by penalties set; nonsmokers president (3%) 32% procedures to resolve disputes Petersen and Only 33% of Health care Located Designated areas only 38%, Employee pressure 43% <3 6% made Massengill smallest (< 50 (93%), retailing where client-contact area 13%B, 1%B (21%), comply years, 53% structural (1986) employees) have (83%), finance workplace entirely, 2% hire only with laws (19%), <6 years changes; 27% policy (61%), smoking law nonsmokers protect employee use barriers manufacturing in effect health (19%), or air (57%), reduce insurance purifiers; 45% transportation costs (9%) discipline (50%), service violators (49%), insurance (18%) respond. An even higher prevalence of smoking policies (64 percent) reported in a survey of large Massachusetts businesses may reflect similar biases or regional variation or both. Smoking policies were reported in only 14 percent of white-collar offices in a nonrandom survey (Thomas 1980) and in 23 to 30 percent of large corporations responding to two nonrandom surveys by the same group (Petersen and Massengill 1986). These surveys found that smoking restrictions were moderate, worksite smoking cessation programs uncommon (9 to 15 percent), and incentives for nonsmoking rare (<3 percent). Outright smoking bans and preferential employment of nonsmokers were not men- tioned. However, employee complaints about smoking were reported by one-third of the businesses in two surveys (Petersen and Massen- gill 1986; Thomas 1980), suggesting a growing pressure on employers for change. Smoking policies were stricter for blue-collar workers and larger worksites (NICSH 1980b; Bennett and Levy 1980). A second set of business surveys, conducted only 5 years later (1984-1986), shows a different picture (Table 4). Three large surveys, two based on random samples, reported a remarkably similar prevalence of workplace smoking restrictions, ranging from 32 to 38 percent (HRPC 1985; US DHHS 1986; BNA 1986). A fourth study reported that 56 percent of small and medium sized businesses had smoking policies, but only 38 percent of businesses restricted smoking to designated areas (Petersen and Massengill 1986). Because of uncertainty in the earlier (1977-1980) estimates, it is difficult to conclude that the most recent estimates of policy prevalence represent an increase. However, there is suggestive evidence on this point: half or more of policies reported in the 1984- 1986 surveys were adopted within 5 years, indicating that the policies are largely products of the 1980s; a sizable number of companies without policies are considering them; in addition to the 36 percent of companies reporting policies in one 1986 report, 2 percent were planning to implement a smoking policy in 1986 and another 21 percent were considering adopting a policy (BNA 1986). Finally, companies that adopt policies rarely reverse them: in the BNA 1986 survey, only 1 percent of companies without policies had ever had one and rescinded it. These data support a contention that workplace smoking policies are a growing trend. The nature and scope of smoking restrictions also changed during the 1980s. The most common policy still restricted smoking to designated areas, but those areas appeared to be shrinking. Despite several well-publicized examples (Pacific Northwest Bell, Group Health Cooperative of Puget Sound), total workplace smoking bans were still rare (1 to 3 percent). An even more stringent smoking policy now being adopted, giving preference to nonsmokers in hiring or refusing to hire smokers, was not even considered less than a 294 decade before (BNA 1986; HRPC 1985; Petersen and Massengill 1986). Fewer than 5 percent of businesses have currently adopted such a policy. Workplace smoking cessation programs were more common, but incentives for nonsmoking remained rare. The 1984-1986 surveys suggest that the diffusion of workplace smoking policies throughout the private sector is occurring in a nonuniform fashion. Companies with policies differ from those without policies in workforce size, geographic location, and type of industry. Smoking policies are slightly more prevalent in large companies than in small businesses (45 versus 33 percent) (Petersen and Massengill 1986; BNA 1986). Policies also differ by company location, being more common in the West and Northeast than in the North Central region or the South (BNA 1986; HRPC 1985). This geographic disparity is similar to the pattern of State smoking legislation, and may in part be explained by it. Businesses in States with workplace smoking laws are more likely to have adopted smoking policies than are companies located elsewhere (HRPC 1985; BNA 1986). Industries are adopting smoking policies at different rates, with more policies and more recent policies in nonmanufactur- ing industries (finance, insurance, health care, pharmaceuticals) (HRPC 1985; Petersen and Massengill 1986; BNA 1986). This represents a shift from the earlier blue-collar predominance of smoking restrictions and reflects the change in policy orientation from workplace safety to employee health. Two factors may explain the growth of workplace smoking policies in the 1980s. Recently enacted State and local workplace smoking legislation is one factor influencing the private sector. Legal mandates are cited as a major reason for adopting policies, and as noted above, the prevalence of private sector smoking policies is higher in regions with legislation in place. Laws may encourage more rapid private action by putting smoking on the corporate agenda. A second factor is public support. Support for an employer’s right to restrict smoking to a designated area at work grew from 52 percent to 61 percent during the 1970s (Roper 1978) and continued to increase in the 1980s (Gallup 1983, 1985). In 1985, 79 percent of U.S. adults, including 76 percent of smokers, favored restricting smoking at work to designated areas. Only 8 percent favored a total workplace smoking ban (Gallup 1985). These attitudes may also be manifest as employee pressures to restrict smoking (Petersen and Massengill 1986; BNA 1986; HRPC 1985). Reasons for Adopting Smoking Policies It is not always easy to identify the motivations and goals for a specific workplace policy (OTA 1986). Explicit reasons for imple- menting policies, according to the most recent employer surveys, are (1) to protect the health of the employee—especially the nonsmok- 295 er—and assure a safe working environment, (2) to comply with State and local statutes mandating worksite smoking policies, and (3) to anticipate or handle demands from nonsmoking employees for a smoke-free working environment. Other reasons may be the fear of possible legal liability for illnesses caused by sidestream smoke exposure in the workplace (Fielding 1982; Walsh 1984), an opportuni- ty to symbolize a company’s concern for employee welfare (Walsh 1984; Eriksen, in press), as part of a general health promotion and wellness program, and the goal of saving the company money. Although it is generally agreed that employees who smoke cost their employers more than do nonsmoking employees, there is as yet little evidence that implementing policies will reduce the extra smoking-related costs (OTA 1986; Fielding 1986; Eriksen, in press). Corporations are keenly interested in stemming the rapid rise in health insurance costs, but may not see smoking policies as a means to that end. The top management at Xerox, for example, rejected a proposed smoking policy because of concerns about the potentially adverse economic impact of excess smoking breaks on productivity (Walsh 1984). Actually, economic considerations do not appear to be a major reason why businesses adopt smoking policies, according to three recent surveys (HRPC 1985; BNA 1986; Petersen and Massen- gill 1986). Barriers to Adopting Smoking Policies Both survey data and case reports give insights into reasons why employers have elected not to implement worksite smoking policies. According to a Tobacco Institute-sponsored survey, the 24 percent of large employers who had considered and rejected a smoking policy gave these reasons: policy not acceptable to employees (59 percent), employees can handle the problem on their own (58 percent), implementation too difficult (39 percent) or too costly (5 percent), policy not acceptable to clients (10 percent), and no employee complaints about smoking (29 percent) (HRPC 1985). Fear of worker discontent or union opposition is the major reason cited by employers who have considered and rejected a workplace smoking policy. Surveys consistently indicate that smoking policies are initiated by management, and are often adopted with little or no employee or union input (HRPC 1985; BNA 1986; NICSH 1980a,b). Although most businesses that have surveyed their employees have found strong support for smoking restrictions (Pacific Telephone 1983; Robert Finnigan Associates 1985, Addison 1984; Ziady 1986; Marvit et al. 1980), some unions have actively opposed employer- mandated policies, both in individual cases and at the national level. In 1986 the AFL-CIO Executive Council stated its opposition to unilateral policies and called for the case-by-case handling of workplace disputes between smokers and nonsmokers (BNA 1986). 296 Both employee organizations and employers find it difficult to simultaneously balance the wishes of all their constituents. Another reason for reluctance to adopt smoking policies is concern about implementation (HRPC 1985). In some cases, this means concerns about how to enforce the policy (BNA 1986) or whether it is enforceable (Eriksen, in press). Other reasons cited by companies were questions about the legality of limiting employee smoking (BNA 1986) and the nonsupport of top management who are smokers (BNA 1986). Some companies are dependent on business relation- ships with tobacco companies and businesses with tobacco-related interests, which they do not want to jeopardize (Kristein 1984; Walsh 1984). Types of Smoking Policies Private sector businesses have addressed the issue of employee smoking in a variety of ways. In addition to smoking policies, the umbrella concept of “worksite smoking control” can include educa- tional campaigns to motivate workers to quit, self-help and organized smoking treatment programs, medical advice, and incentives to encourage nonsmoking (Orleans and Shipley 1982; Windsor and Bartlett 1984). Smoking programs are sometimes subsumed as part of broader corporate wellness programs. Worksite smoking cessation programs were reviewed in the 1985 Report on the Health Conse- quences of Smoking (US DHHS 1985c). Businesses have taken a variety of approaches to a worksite smoking policy. The chcives reflect the individual company’s motive in adopting a policy and assessment of the potential for implementa- tion and enforcement. When protection from fire or explosion was the primary motive, policies primarily applied to blue-coilar areas; when the goal was to avoid antagonizing customers, smoking bans applied only to client-contact areas (Bennett and Levy 1980). A company’s solution also reflects its particular social environment. Recent study indicates considerable variability among individual worksites in attitudes and norms about smoking cessation (Sorensen et al. 1986). Because smoke travels, the desires of smokers and nonsmokers will inevitably come into conflict in common areas, and it is difficult to simultaneously maximize the goals of smoke-free air, minimum employee disruption, and minimum cost. A business adopting a policy primarily to avoid employee conflicts is likely to pay greater heed to smokers’ wishes at the expense of smoke-free air, and may consider solving the problem with increased ventilation (to avoid the necessity of behavioral change) or may separate smokers and nonsmokers. A business whose primary goal is to reduce involuntary smoking hazards will be more willing to sacrifice smokers’ conve- nience and may consider a total smoking ban. A business that aims 297 to reduce costs may choose a minimum of structural changes and a maximum likelihood that the policy will result in employee smoking cessation; a total ban on workplace smoking or the hiring of only nonsmokers would be more likely to achieve these goals. Alternative- ly, adopting no policy may also be inexpensive, so long as there are no employee conflicts over smoking. The myriad of current smoking policies have been categorized in several ways (US DHHS 1985a; BNA 1986; OTA 1986; ALA 1985a,b). The range, in ascending order of protection for the nonsmoker, includes these: (1) No explicit policy (the “individual solution” approach) (2) Environmental alterations (separating smokers with physical barriers, using air filters, or altering ventilation) (3) Restricting employee smoking, a range with these extremes: (a) smoking permitted except in designated no-smoking areas (b) smoking prohibited except in designated areas (4) Banning employee smoking at the worksite (5) Preferential hiring of nonsmokers. Options (1) through (3a) effectively state that smoking at work is acceptable behavior; options (3b) through (5) indicate to employees that nonsmoking is the company norm. Several groups have developed model policies of varying degrees of comprehensiveness to assist employers (ALA 1985a,b; GASP 1985; BNA 1986; Hanauer et al. 1986). The “Individual Solution” Approach According to surveys, having no explicit policy is still the most prevalent approach to smoking in the workplace (HRPC 1985; BNA 1986; US DHHS 1986). Smokers and nonsmokers work out differ- ences on their own, using so-called common courtesy or finding an individual solution. According to a 1984 Tobacco Institute-sponsored survey, 70 percent of large employers encourage employees to work out differences on their own (HRPC 1985). When there is no explicit policy, there is the implicit message that environmental tobacco smoke does not represent a hazard. So long as there are few disputes and they are easily settled, this approach is expedient. However, it is not likely to be a successful long-term policy. Nonsmokers in the late 1970s may have been reticent to assert their rights and perceived a burden of confrontation (Roper 1978; Shor and Williams 1978), but there is a growing consensus, even among smokers, that supports abstention in the presence of nonsmokers and smoking restrictions at worksites (Gallup 1983, 1985). 298 Environmental Alterations Environmental alterations range from simply separating smokers and nonsmokers to different areas of a room to installing improved ventilation systems to remove environmental tobacco smoke. The advantage of this approach is that it requires no behavioral change of smokers and satisfies some of the wishes of nonsmokers. However, because tobacco smoke easily diffuses beyond physical boundaries, simple barriers provide at best a slight reduction in involuntary smoke exposure (see chapters 3 and 4) (Olshansky 1982). More sophisticated ventilation systems can be prohibitively expensive, and even the best may not be able to clean the air adequately (Repace and Lowrey 1985; Lefcoe et al. 1983). Workplace modification has sometimes been utilized as a company’s first step in the development of a more restrictive policy, as happened at the Control Data Corporation in Minneapolis (OTA 1986). Restrictions on Employee Smoking The most common workplace smoking policy is to restrict where employees may smoke (BNA 1986). This policy has broad public support; in a 1985 Gallup poll it was the approach favored by 79 percent of U.S. adults, including 76 percent of smokers (Gallup 1985). Policies differ in (1) the proportion of the workplace in which smoking is permitted, (2) whether the default condition is smoking, nonsmoking, or unspecified, (3) who has the authority to designate the smoking status of an area, and (4) whose wishes prevail when smokers and nonsmokers disagree. Policies often categorize the worksite into four areas that are subject to different rules: (1) private offices, (2) shared offices or work areas, (3) small common use areas (elevators, bathrooms), and (4) large common use areas (conference and meeting rooms, auditoriums, cafeterias). The least restrictive policies permit smoking except in designated no-smoking areas, indicating that smoking is the company norm. Who has the authority to designate an area’s smoking status and whether smokers’ or nonsmokers’ wishes prevail may not be explicit. The usual pattern is for common use areas to be designated either totally no-smoking (elevators, bathrooms, conference rooms) or partly no-smoking (cafeterias, auditoriums). Private offices are left to the discretion of the occupant, who is often given the authority to declare it no-smoking. In shared office areas, where the wishes of smokers and nonsmokers may conflict, each individual may be given the authority to designate his or her own immediate work area, or the policy may stipulate that a compromise be reached. However, this cannot ensure that an employee's self-designated no-smoking area is free of sidestream smoke. Because the majority of an employee’s time is spent in the immediate work area rather than in 299 the no-smoking common use areas, a policy that does not specify no- smoking in shared work areas may not substantially reduce an employee’s environmental tobacco smoke exposure. However, these policies may satisfy some nonsmokers’ wishes with minimal disrup- tion to smokers. In some cases, companies seeking to limit smoking have adopted this type of policy as a first step to more stringent restrictions or a total ban (e.g., Boeing, cited in OTA 1986). The most restrictive policies specify that “smoking is prohibited except in designated areas,” establishing nonsmoking as the work- place norm. In the strictest policies, smoking is prohibited in shared work areas (unless all occupants agree to designate an area “smoking permitted”) and in most common use areas. Policies may limit the areas that can be designated “smoking permitted” and predetermine that the wishes of nonsmokers prevail when conflict occurs. Even stricter regulations stipulate not only the location in which but also the time when smoking is allowed (e.g., work breaks only). So long as the smoking areas do not contaminate the air of work areas, these policies provide greater protection of employees from sidestream smoke at the cost of greater inconvenience to smokers, who may perceive the restrictions as coercive. The produc- tivity of smokers may suffer if they are permitted to take extra smoking breaks or if smoking areas are ivated too far from the work station. The variability of smoking restrictions in common work areas was demonstrated in a 1985 survey conducted by the Bureau of National Affairs, Inc. (BNA). Of the 239 companies with smoking policies, 41 percent banned smoking in open work areas, and an additional 20 percent banned it if employees or supervisors wished. Only 8 percent permitted smoking in all open work areas, and 19 percent divided areas into smoking and no-smoking sections. There was more uniformity in treatment of common use areas. Over 50 percent of the companies banned smoking in hallways, conference rooms, rest- rooms, and customer contact areas, and smoking was partially banned in 58 percent of cafeterias (BNA 1986). In contrast to shared work areas, smoking was permitted in 56 percent of the private offices in that survey, with occupants often given the authority to designate the office as smoking or no-smoking. This has the potential for charges of unequal treatment and problems with employee morale (BNA 1986). Banning Smoking at the Workplace Some businesses—including large corporations, among them Pacif- ic Northwest Bell and the Group Health Cooperative of Seattle— have recently opted for total bans on smoking at work (US DHHS 1985a; Ziady 1986). Bans may be preceded over several years by progressively stricter smoking regulations. Notwithstanding these 300 well-publicized successful examples, smoking bans are rare and not widely supported by public opinion. Only 6 percent of companies with smoking policies (2 percent of all respondents) in a 1986 survey totally banned smoking (BNA 1986). Only 12 percent of adults (4 percent of smokers) agreed that “companies should totally ban smoking at work” in a 1985 Gallup poll. In spite of this hesitancy, smoking bans are gaining momentum among large employers such as Boeing, who recently announcéd an upcoming ban that will cover its 90,000 employees (Iglehart 1986). Smoking bans provide the maximum protection for nonsmokers, at the cost of greater inconvenience for smokers. They send a clear message that nonsmoking is the company norm. They can reduce ventilation needs and maintenance costs due to smoking, but pose potential problems with enforcement and loss of employees who smoke. Thus, how a ban is planned, prefaced and introduced, and implemented and enforced is very important. Through a concern for employee well-being, assistance for smokers who wish to quit should be implemented along with bans (Orleans and Pinney 1984). Preferential Hiring of Nonsmokers The most restrictive workplace smoking policy, preferential hiring of nonsmokers, was not even discussed several years ago. Explicit policies favoring nonsmokers are still uncommon. According to the 1986 report of the Bureau of National Affairs, Inc., 1 percent of businesses hire only nonsmokers, 5 percent give nonsmokers prefer- ence, and 10 percent permit supervisors to exercise a nonsmoking preference (BNA 1986). The majority either have no policy (43 percent) or do not permit such a preference (39 percent). On the other hand, data from small surveys indicate that personnel managers, the majority of whom are themselves nonsmokers, may preferentially hire nonsmokers (Weis 1981; Iglehart 1986). In a unionized setting, selective hiring of nonsmokers may need to be the subject of collective bargaining (Eriksen, in press). Hiring only nonsmokers ensures a smoke-free work environment without conflicts over smoking and makes it clear that nonsmoking is the company norm. Since the nonsmoking workforce should be healthier, lower health insurance premiums may also result. On the other hand, such a policy limits the potential pool of new employees, raises the issue of what to do about currently employed smokers, and may present problems with verification of smoking status. Employ- ers may be reluctant to adopt a policy in which off-the-job activity is a condition of employment (Walsh 1984). Assuring compliance with workplace smoking policies is complex. Model policies usually include three enforcement provisions: (1) identifying who is responsible for policy enforcement, (2) designating penalties for noncompliance, and (3) ensuring the protection of an 301 employee bringing a complaint. These provisions are often not included in practice. Only 23 percent of the policies stipulated penalties for noncompliance and only 32 percent specified proce- dures for resolving disputes in the 1986 BNA survey. Approximately half of the policies outlined in two other business surveys had provisions for disciplining violators (Petersen and Massengill 1986; NICSH 1980a,b). Implementation of Smoking Policies Worksites that have adopted smoking policies have differed in the ease with which policy was implemented. To aid employers, the American Lung Association and the Office of Disease Prevention and Health Promotion of the U.S. Department of Health and Human Services have developed guides with specific recommendations on how to adopt and implement worksite smoking policies (ALA 1985b; US DHHS 1985a). These are based on the experience of companies and can be extremely helpful even though they are not based on research. The experiences of 12 corporations that considered smoking policies are described in a report of the Bureau of National Affairs, Inc. (1986). Case reports are also included in the guide from the Office of Disease Prevention and Health Promotion (US DHHS 1985a). According to these case reports, strong support from top management and having an advisory committee composed of a wide variety of employees (including both smokers and nonsmokers, managers, and employee representatives) are common to successful policies. Surveys of employees can assess distress caused by involun- tary smoking and support for policy changes. As a rule, such surveys have generally documented widespread support for smoking restric- tions from employees, the majority of whom are nonsmokers. Another correlate of success is . well thought out and clearly articulated communication of the policy. A written document should give the rationale for the policy implementation, specify where smoking will be allowed or prohibited, and define responsibility and procedures for policy enforcement and penalties for violation. Successful policies avoid criticizing smokers or setting up an antagonistic situation between smokers and nonsmokers. They make it clear that the company is not requiring that employees quit smoking and will help smokers in adjusting to the new regulations. Giving smokers advance notice of the policy and providing help for those who want to quit smoking can help gain their support. Careful plans for implementation are recommended. Allowing several months between the announcement of the policy and its effective date gives smokers time to prepare for the change and to attend smoking cessation programs if tney wish to quit. This also provides time for the posting of adequate numbers of signs and for 302 ‘making any structural alterations that may be necessary. After policy implementation, an advisory committee should monitor its effectiveness and enforcement. A followup survey is helpful to determine what, if any, adjustments need to be made. Impact of Policies Restricting Smoking in Public Places and in the Workplace Policies that regulate where smoking is permitted may have a number of direct and indirect effects. In the short term, a policy that is adequately implemented and enforced will alter the behavior of smokers in areas where smoking is prohibited and should result in a reduced concentration of tobacco smoke in that area. Beyond these direct effects, there is the potential for smoking restrictions to have broader, indirect effects on smoking behavior and on public attitudes about tobacco use. This section outlines the possible impacts of smoking policies, addresses methodologic considerations, and re- views existing data that bear on these hypotheses. Potential Impacts of Smoking Policies Policy Implementation and Approval The degree to which a smoking policy or law has been implemen- ted as written is an essential consideration in evaluating its effects on attitudes, behavior, and air quality. Successful implementation involves public awareness of the policy, compliance with its regula- tions, and enforcement of violations. Compliance requires not only that smokers refrain from smoking where prohibited from doing so, but also that appropriate decisionmakers develop written policies, designate areas as no-smoking, and post signs as stipulated. Enforce- ment requires that policy violations be dealt with, either by peer action or by penalties defined by the policy. Because smoking policies and laws are approved by the majority of individuals whose behavior they affect, they are generally held to be self-enforcing, obviating the need for active policing (Hanauer et al. 1986). When enforcement is needed, smoking policies and legislation rely primarily on peers, assuming that the nonsmoking majority of the population will enforce the policy or statute because it is in their best interest. Nonsmokers can be expected to favor smoking restrictions, which offer the benefits of cleaner air and reduced health risks and require no change in their behavior. The opinions of smokers are expected to be less favorable because they stand to be inconvenienced. Some smokers may support the policy to assure themselves of having a location where smoking is clearly permitted, because of a desire to quit smoking, or because of concerns about the health hazards of involuntary smoking. The degree of smokers’ support for a policy 303 may also depend on other factors, such as the degree of smoking restriction or the adequacy of policy implementation. Direct Effects: Air Quality and Smoking Behavior The evaluation of a specific policy or piece of legislation must address whether the policy achieved its stated goals and must also screen for other effects. The primary goal of policies regulating smoking in public places or in the workplace is the reduction of individuals’ exposure to environmental tobacco smoke. Measures of air quality directly assess how well a policy meets this goal. Air quality also indirectly reflects the behavior of smokers and the degree of policy compliance. Smoking policies may have both direct and indirect effects on smoking behavior. The direct effect of adequately implemented smoking restrictions is to limit where smoking is permitted, altering the behavior of smokers in those settings. Smoking policies may have indirect effects on smoking behavior if they influence the behavior of smokers outside these settings. Indirect Effects: Knowledge, Attitudes, Social Norms, and Smoking Behavior Policies that restrict or ban smoking in public places or the worksite convey potentially powerful messages about the role of cigarettes in society and help to reinforce nonsmoking as the normative behavior. Restricting smoking to protect nonsmokers may increase public knowledge of the health risks of smoking and of involuntary smoking. Smoking restrictions may also alter attitudes about the social desirability of smoking and the acceptability of smoking in public. Changes in the knowledge or acceptance of health risks combined with attitude shifts contribute to changing social norms about where smoking should and should not occur, as well as whether it is an acceptable social behavior. Changes in social norms may influence smoking behavior by reducing pressures to smoke and increasing social support for nonsmoking and cessation. The combination of altered social norms and reduced opportunities to smoke may encourage smokers to quit and discourage experimentation among nonsmoking youth. Chang- ing social norms may have their greatest impact on teenagers and young adults, who might be less inclined to experiment with a socially undesirable substance. Current smokers are likely to be prompted by changing social norms to move further through the stages of self-change that precede cessation (Prochaska et al. 1985). Smoking restrictions may influence smoking behavior apart from their influence on social norms. By reducing opportunities for smoking, restrictions may decrease a smoker’s daily cigarette 304 consumption. By reducing the range of settings where smoking occurs, they reduce the cues and alter the stimulus-response patterns that help to maintain smoking behavior and that contribute to relapse among ex-smokers (Orleans 1986). This could increase the success of quit attempts. Smoking restrictions, especially those at the workplace, may also help smokers to discover alternatives to smoking as a stress reduction tool. Likewise, new entrants into the workforce may not as easily learn to rely on cigarettes to cope with work-related stressors. This might blunt the increase in smoking prevalence that occurs at the time of workforce entry, especially among blue-collar workers (O’Malley et al. 1984; US DHHS 1985c). Thus, the widespread adoption of smoking restrictions may have a profound impact on smoking behavior at many points in its natural history. Hypothesized consequences include reduced cigarette con- sumption, increased motivation and progress through the stages of self-change, increased rates of smoking cessation, and decreased rates of smoking initiation. Smoking policies may have additional impacts beyond their effects on attitudes and smoking behavior, such as positive economic effects for employers by reversing the excess costs associated with employ- ees who smoke. It is generally agreed that employees who smoke cost their employers more than nonsmoking employees because of excess absenteeism, increased health care utilization, and reduced produc- tivity (OTA 1986; Fielding 1986; Eriksen, in press). This leads to greater use of sickness, disability, and health care benefits and ultimately, higher health insurance costs to business. Productivity losses to business are attributed not only to the individual smoker’s time lost owing to on-the-job smoking, but also to increased maintenance costs due to cigarette-related damage and refuse. Estimates of the excess annual cost per smoking employee vary by an order of magnitude, but even conservative estimates are substan- tial: $300 to $600 (Kristein 1983, 1984; Solomon 1983; Weis 1981). Reductions in health care costs are partly dependent on whether policies lead smokers to quit smoking. Even if smokers quit, the reduction in health care costs may not be seen in the short term. Some employers have been concerned that strict smoking bans may unfavorably alter employee turnover patterns or productivity. Smokers’ productivity could decrease if, for example, they are permitted to take extra breaks away from their work stations in order to smoke (OTA 1986; Michigan Tobacco and Candy Distribu- tors and Vendor Association 1986). Cests involved in adopting a smoking policy should also be considered. Assessment of these endpoints is useful because employers may consider them in deciding whether to implement smoking policies. 305 Methodologic Considerations in Policy Evaluation Study Design _ Evaluating a new smoking policy in a defined population is similar to evaluating a smoking cessation intervention, with the addition of nonsmokers. Impacts on beliefs and attitudes, as well as on behavior, can be assessed in the population at baseline and at intervals after implementation. Because smoking policies may influence smoking behavior gradually, designs must be able to measure delayed effects. Simultaneous assessment of outcomes in a control population strengthens confidence in the validity of conclusions. With uncon- trolled pretest/posttest designs, there is the possibility that changes in smoking behavior and attitudes are confounded by outside influences. Worksites, for example, may have concurrent smoking cessation programs that can affect attitudes and behavior. Popula- tionwide trends in smoking behavior are another source of confoun- ding. In practice, random assignment of whole populations will rarely be feasible, since researchers are rarely in a position to “assign” the intervention and must rely on natural experiments. Quasi-experimental designs, which include natural comparison groups, are the best alternative. Identifying and accessing such appropriate comparison populations may be difficult in practice. Either longitudinal or cross-sectional sampling can be employed. Longitudinal designs, in which the same individuals are interviewed at two or more points in time, provide the best measure of changes in outcome measures, but depend on high rates of followup, which may be practically difficult. Furthermore, individuals’ behavior or atti- tudes may be influenced by repeated assessments in such studies. On the other hand, when attitudes and behavior are evaluated by repeated assessments of independently chosen cross-sectional sam- ples, the possibility exists that smokers and nonsmokers will enter or leave the population at different rates as a consequence of smoking restrictions. Turnover needs to be followed to assure that changes in behavior or attitudes are a result of changes in individual behavior and not changes in the composition of the population. One-time comparisons of populations with and without policies can provide suggestive but not conclusive data about impact. The validity of differences detected in attitudes and behavior is depen- dent on the degree of similarity between the policy group and the control group. Uncontrolled one-time assessments done before or after policy adoption do not permit conclusions about the policy effects, although they may provide hypotheses for further work. Postimplementation surveys of a population can, however, provide useful information about the degree of policy approval, awareness, compliance, and enforcement. Assessment of the impact of legislation on smoking behavior is more difficult because the unit of study is larger and more diverse. 306 Consequently, detailed behavioral or attitudinal data and repeated assessments are more difficult to obtain. Evaluations are often limited to analyses of aggregate measures such as smoking preva- lence and tobacco consumption, which are collected for other purposes. This approach does not control for potentially confounding influences on tobacco use or smoking behavior, such as price fluctuations. Identifying and assessing control groups not subject to smoking legislation or regulation can strengthen the confidence in conclusions for the same reasons as above, but is often difficult to achieve in practice. Assessing the Effects of Smoking Policies Ideally, air quality should be measured objectively, but current technology for measuring the concentration of tobacco smoke in indoor air is expensive and cumbersome. There is also uncertainty about which constituent of smoke is best to measure (See chapters 3 and 4 of this volume). Air quality can also be assessed subjectively. Ratings made by occupants of smoke-free areas can be compared with those of a control area or to ratings made prior to the ban. Measurement of an individual nonsmoker’s actual exposure to secondhand smoke, using biochemical measures, is not a specific measure of the concentration of this smoke in a single area because an individual may have other sources of smoke exposure. Such measures might be useful for assessing the concentration of smoke in areas, like the worksite, that represent a primary source of exposure. They cannot be used to measure air quality in other places, like an auditorium, where an individual spends only a few hours. Many markers of smoking behavior need to be examined in order to understand the multiple effects of smoking restrictions on behavior. In a defined population, a new policy may increase smokers’ motivation to quit, confidence in their ability to quit, or the number, duration, and success of quit attempts. It may also reduce cigarette consumption among continuing smokers. Workplace poli- cies may have different impacts on cigarette consumption at work and outside work. These variables should be separately assessed. As in other research in smoking behavior, biochemical verification of self-reported smoking status is desirable. Public knowledge about the health risks of involuntary smoking and attitudes about smoking can be assessed by surveys. Data on social norms can be construed from survey items such as those measuring the social acceptability of smoking in public places or in the presence of nonsmokers, the rights of nonsmokers to smoke-free air, the perceived prevalence of smoking in the environment, and the perceived social support for cessation or nonsmoking. The adequacy of a policy’s implementation can be assessed by surveys that measure individuals’ knowledge and compliance with a 307 policy. The degree of noncompliance and enforcement can also be assessed by observations of behavior in public places subject to smoking restrictions. Review of Current Evidence on Impact Workplace Smoking Policies In 1982, Orleans and Shipley concluded that the evaluation of worksite smoking policies was limited to a few public opinion polls. Since then, many policies have been adopted, but evaluation remains rare. Most common are baseline surveys done by companies consider- ing smoking policies. The best surveys utilize random or probability samples and achieve high rates of completion; they provide useful one-time data on attitudes and behavior prior to policy implementa- tion. Unfortunately, few companies adopting smoking policies have done postimplementation surveys to assess impact. To date, the best evaluations of worksite smoking policies have been done in the health care setting. There are two controlled and two uncontrolled studies assessing the effects on employees of adopting a smoking policy for a hospital (Rigotti et al. 1986; Biener et al. 1986; Andrews 1983; Rosenstock et al. 1986). One uncontrolled study was renorted by Andrews (1983). He described the process by which the New England Deaconness Hospital in Boston adopted a restrictive smoking policy in 1977. Patients and employees were surveyed prior to the policy. Employees were surveyed again 20 months after the policy took effect. The survey method and response rate were not specified; presumably it was not a random sample. Policy approval and smoking behavior were assessed. The second uncontrolled study (Rosenstock et al. 1986) evaluated the impact of a near-total smoking ban adopted in April 1984 by the Group Health Cooperative of Puget Sound, Washington, the fourth largest health maintenance organization in the Nation. Four months after the policy was adopted, they surveyed a systematic probability sample of 687 employees, assessing smoking behavior, attitudes toward the policy, and its effect on work performance. Employees were asked retrospectively about attitudes and behavior prior to the policy. The response rate was 65 percent. The two controlled studies of the impact of adopting a restrictive hospital smoking policy are similar in design. Both involve prepolicy and postpolicy measurements of intervention and control groups and assess similar outcomes. Rigotti and colleagues (1986) studied the impact of a total ban on smoking adopted in November 1984 by the pediatric service at Massachusetts General Hospital in Boston. All nurses employed by the service were surveyed at baseline and at 4 and 12 months. Nurses working on the hospital’s medical service, where no policy change occurred, were surveyed concurrently as 308 controls. Response rates to the surveys ranged from 55 to 75 percent; the prevalence of smoking among respondents and nonrespondents did not differ. Surveys assessed smoking behavior, attitudes about smoking, and perceived air quality in both groups. The pediatric nurses answered additional questions about approval, compliance, and awareness of the policy. Employment records were reviewed to assess employee turnover before and after the policy. Biener and colleagues (1986) studied employees at two Providence, Rhode Island, hospitals where self-help smoking cessation programs were being introduced. At one, the Miriam Hospital, there was a concurrent change in smoking policy. Smoking was prohibited hospitalwide except in three locations as of August 1985. Separate random probability samples of 85 employees at each hospital were surveyed by telephone at baseline (2 to 4 weeks before the policy) and at 1, 6, and 12 months after the policy. Data were collected in both hospitals on smoking behavior, attitudes about smoking, and air quality. Information on policy awareness, compliance, and approval was obtained at the intervention hospital. Results of these studies are included in the subsequent sections, which address the outcomes of workplace smoking policies. Policy Implementation According to case reports, organizations that have adopted smok- ing control policies generally develop careful plans to introduce the policy, but rarely evaluate how effectively the policy has been implemented. The findings of Rosenstock and colleagues (1986) indicate that even careful implementation plans may fall short of their goals. In their survey of the Group Health Cooperative employees, only half of the respondents knew of the existence of the advisory group whose role was to provide information to employees. Only 36 percent of the smokers and 76 percent of the nonsmokers felt that they had had an adequate opportunity to express their views. Not all smokers knew that the decision to prohibit smoking was an irrevocable one. Rigotti and colleagues (1986) found that awareness of the smoking ban on the pediatric service was high; at 4- and 12-month followups, over 90 percent of employees knew where smoking was not permit- ted. Employees noted smoky air or smoking in restricted areas on approximately 20 percent of days worked. Two-thirds of the employ- ees who smoked admitted at least one personal episode of noncompli- ance during the year after the policy took effect. Although nonsmok- ers perceived themselves to be more assertive in enforcing smoking rules after the smoking ban, many were reluctant to confront a smoker, especially if the smoker was a coworker. Biener and colleagues (1986) found a similar high level of policy awareness and better compliance among the employees of Miriam 309 Hospital in Providence. Six months after the adoption of a policy prohibiting smoking in all but three areas, 95 percent of the employees were aware of the policy and half had noted no evidence of noncompliance. There was no evidence that smokers perceived more pressure to abstain in the form of increased assertiveness by nonsmokers; the policy may have reduced the need for assertive behavior. Rigotti and colleagues (1986) reported that nurses in the control group described themselves as having to be more assertive about asking people not to smoke than nurses in the policy group. Dawley and colleagues (Dawley et al. 1980; Dawley, Carrol et al. 1981; Dawley, Morrison et al. 1981; Dawley and Baldwin 1983; Dawley and Burton 1985) addressed the question of compliance with smoking restrictions at the New Orleans Veterans’ Administration Medical Center. Their technique was to unobtrusively observe the smoking behavior of individuals occupying areas designated as smoking or no-smoking. In a series of 10-minute periods, an observer noted the proportion of people smoking among all individuals occupying a no-smoking area, which served as the measure of noncompliance. Posting no-smoking signs in a hospital lobby reduced the prevalence of smoking to one-third of its previous level (from 29 percent to 5 to 11 percent, p< 0.01). There was a nonsignificant trend for better compliance with positively worded signs (e.g., “Please do not smoke”) compared with negatively worded signs (e.g., “No smoking—Offenders subject to fine”) (Dawley, Morrison et al. 1981). Posting signs designating a no-smoking area in a cafeteria resulted in a similar decline in smoking prevalence in the area. The combination of signs and enforcement (polite reminders from staff to noncompliant patients) achieved greater reductions in smoking prevalence than were achieved with signs alone; however, the incremental value of enforcement was not directly assessed in the study (Dawley and Baldwin 1983). Following a change to a more restrictive smoking policy (smoking prohibited except in designated areas, with provisions for enforcement), the noncompliance rate dropped to under 2 percent (Dawley and Burton 1985). Another study demonstrated that smoking models reduce compliance with smoking restrictions. The noncompliance rate doubled when a smoker was experimentally introduced into the no-smoking area (Dawley, Carrol et al. 1981). These studies indicate that there has been good employee compli- ance with smoking policies in health care facilities, even though there may be some reluctance by employees to enforce restrictions. The implementation of smoking policies in other types of worksites has not been systematically evaluated. Descriptions of the adoption of policies in a number of worksites do not report major problems with compliance (BNA 1986). 310 Air Quality Three studies assessed air quality before and after hospitals adopted restrictive smoking policies. Both Rigotti and colleagues (1986) and Biener and colleagues (1986) used a subjective measure, the frequency that an employee was bothered by smoke at work. In the Rigotti group’s study, perceived air quality was similar in the intervention group and the control group at baseline. It improved significantly at 4- and 12-month followup on floors where smoking was banned and did not change on control floors. At 12 months, 79 percent of the nurses on floors with the smoking ban reported noticing less smoke, and none noted an increase; in contrast, 87 percent of control nurses noted no change in air quality. Biener and colleagues found a similar pattern; there was a significant difference in employee assessments of perceived air quality between hospitals with and hospitals without a smoking policy. At the New England Baptist Hospital in Boston, the distribution of respiratory particulates (RSP) was measured before and 1 year after the adoption of a restrictive smoking policy (Bearg 1984). At followup, RSP were lower in many hospital areas where smoking was restricted, most notably in patient care areas and an employee lounge, but remained high in the cafeteria. Because same-day measurements of outside air revealed low ambient RSP levels, Bearg concluded that the high levels inside the building were attributable to smoking rather than air pollution. These studies suggest that hospital policies result in less smoking in work areas designated no-smoking, but that no-smoking areas in cafeterias may provide little protection from secondhand smoke exposure because of ventilation problems and the increased smoking in the few smoking-permitted areas. Policy Approval A number of private and public sector organizations considering a smoking policy have assessed employee attitudes prior to implemen- tation. Pacific Northwest Bell, Pacific Telephone, New England Telephone, Texas Instruments, and StrideRite are among businesses that have done employee surveys (R. Addison, personal communica- tion, July 21, 1986; Pacific Telephone 1983; Robert Finnegan Associates 1985; BNA 1986; Ziady 1986). Public sector employers include the Hawaii and Massachusetts Departments of Public Health (Marvit et al. 1980; Naimark 1986). The findings of these surveys are remarkably similar. Over 60 percent of employees report being at least occasionally bothered by smoke at work (Robert Finnegan Associates 1985; Pacific Telephone 1983; Ziady 1986; R. Addison, personal communication, July 21, 1986). There is broad support for adopting a smoking policy, even among smokers (Pacific 311 Telephone 1983; Robert Finnegan Associates 1985; Marvit et al. 1980, Sorensen and Pechacek 1986). Assessment of employees’ approval of policies after implementa- tion have been done primarily in health care settings. High rates of approval are the uniform finding, with smoker-nonsmoker differ- ences. In the Rigotti group’s study (1986), the overall approval of a smoking ban increased from 72 percent at baseline to 85 percent at 4 and 12 months. Most of the increase was a result of the improved opinions of the smokers. Only 35 percent of smokers supported the ban at baseline, but by 1 year this nearly doubled, to 67 percent. High rates of policy approval at followup by both smokers and nonsmokers were also reported by Biener and colleagues (1986) (69 percent smokers, 89 percent nonsmokers) and Andrews (1983) (83 percent smokers, 93 percent nonsmokers). Rosenstock and colleagues (1986) found high overall policy approval at 4 months (85 percent), but less support by smokers (36 percent). These data indicate that smoking policies in hospitals are well accepted by employees, and that smokers’ initial reluctance diminishes as they gain experience with the policy. Generalization from these studies is limited by the nature of the population studied—health care workers. Followup surveys in industrial setting would be valuable. Sorensen and Pechacek (1986) have examined correlates of smok- ers’ approval of smoking restrictions. They surveyed smokers in eight Minnesota businesses without smoking policies, sampling a broad cross-section of employees, from blue-collar workers to profes- sionals. Over three-fourths of the 378 respondents agreed that employers should establish separate smoking and no-smoking areas at work. Smokers who favored worksite smoking policies had greater interest in quitting and more concern for the health risks of smoking and saw their social environment as supportive of nonsmoking, as measured by a higher perceived coworker support for quitting anda greater perceived prevalence of nonsmokers. Smoking Behavior Many smokers anticipate that their smoking behavior will change after a smoking policy is adopted at their worksite. At Pacific Telephone, 51 percent of the smokers expected that the policy would lead them to alter their smoking habits, either by cutting down (38 percent) or quitting (13 percent) (Pacific Telephone 1983). In the Rigotti group’s study (1986) of a hospital smoking ban, 72 percent of the smokers expected the policy to change their habits. All expected to smoke less at work and most to smoke less outside work. A successfully implemented smoking policy will provide a smoker fewer opportunities to smoke. Of course, the smoker may compen- sate for reduced smoking opportunities at work by more intense smoking (number of cigarettes, inhalation, puff topography) on 312 breaks or with increased smoking outside work to maintain a constant overall daily consumption. This is consistent with the addictive model of smoking behavior (Gritz 1980; US DHEW 1979). But if compensation does not occur, the smoker’s lower rate at work would reduce overall daily smoking. Studies at present differ on which of these alternatives occurs. The results reported below are entirely self-reports; thus, they suffer from a lack of biochemical validation of smoking status as well as from an inability to detect compensation through altered smoking topography (US DHHS 1985c). Compensation did not appear to occur in the Biener group’s hospital study (1986). Among smokers in the “policy” hospital, the number of cigarettes smoked daily while at work fell from a baseline of 8.1 to 4.5 at 1 month and 4.0 at 6 months. Over the same time period, the at-work cigarette consumption in the control hospital rose slightly (7.6 to 8.1 cigarettes). The difference in smoking rates between baseline and 1-month followup in the “policy” group was significant (p=0.02). At 6 months, the difference in smoking rates at work between hospitals (8.2 vs. 4.0) was also significant (p=0.01). There were no significant changes in the smoking rate outside work. Smokers in the hospital study by Rosenstock and colleagues (1986) reported smoking a mean of 15.6 cigarettes daily, 2 fewer than before the policy (p<0.003). These data suggest that smokers did not compensate for reduced smoking opportunities at work by increasing their smoking at home. Rigotti and colleagues (1986) found indirect evidence for compen- sation. The nurses’ self-reported cigarette consumption at work decreased in the policy group, but did not change in the control group. However, overall cigarette consumption in the policy group did not change. Both the degree of change and the number of smokers in the study were small. In an earlier study, Meade and Wald (1977) compared the smoking behavior of three British employee groups. Smoking was prohibited at work for two groups. Smokers who were allowed to smoke at work had a somewhat higher self-reported average daily cigarette con- sumption. The maximum rate of smoking occurred at work in the afternoon, but for workers prohibited from smoking at work, the maximum rate occurred in the interval between leaving work and retiring at night. There has been much speculation that smoking policies will increase the smoker’s motivation and success in quitting. In the study by Biener and colleagues (1986), the percentage of smokers considering quitting in the next 6 months increased from 71 percent at baseline to 91 percent at followup, but there was no change in motivation in the control hospita! group. Two-thirds of the smokers in Rosenstock and colleagues’ uncontrolled study (1986) had a 313 definite desire to quit. However, Rigotti and colleagues (1986) found no difference in the motivation of nurses between the control group and the policy group. Smokers’ use of worksite smoking cessation programs before and after policies go into effect have been used as an index of their motivation to quit smoking. The results are mixed. In the 6 months after Pacific Northwest Bell adopted a smoking ban in October 1985, 1,044 employees, representing 25 percent of all smokers, enrolled in programs reimbursed by the company. This compared with 331 who attended free onsite programs in the previous 26 months. The cost to the company per smoker was $142 (Martin 1986, K. Rowland, memorandum for Len Beil, April 25, 1986). At Texas Instruments (R. Addison, personal communication, July 21, 1986), 486 smokers enrolled in cessation classes within the first year after the announce- ment of a smoking policy; this compares with only 11 in 1982, the last year for which statistics were kept. In both cases, this enthusias- tic response may in part be due to the employers’ new willingness to pay for the classes, as well as to the incentive provided by a new policy. For example, only 8 of 148 smokers at the New England Deaconness Hospital who said they were interested in a smoking cessation program on their own time actually showed up (Andrews 1983). Even company sponsorship is not a guarantee of popularity. At the Group Health Cooperative, only two smokers aware of the company-sponsored cessation programs had participated within 4 months of policy adoption (Rosenstock et al. 1986). The signup rate for worksite-based self-help smoking cessation programs was no greater at a Rhode Island hospital with a new smoking policy than at one without (Biener et al. 1986). It is not known whether the cessation rate of smokers who enroll in worksite programs is affected by the presence of a smoking policy at the worksite. Only uncontrolled studies with self-report measures are currently available. At Texas Instruments (R. Addison, personal communication, July 21, 1986), 34 percent of 354 employees enrolled in the first round of company-sponsored cessation classes quit smoking by the end of the program; in the second round of classes, 17 percent of 132 enrollees quit. At Pacific Northwest Bell, 44 percent of 639 respondents quit smoking in a survey of the 1,200 participants in a company-sponsored program. If nonrespondents are included as smokers, the cessation rate was 23 percent (Shannon 1986). There is as yet no conclusive evidence that smoking policies are associated with increases in smoking cessation attempts or reduc- tions in smoking prevalence. All reports are based on self-reported smoking behavior. There are anecdotal reports of smokers quitting in case reports of company policies (StrideRite, cited in BNA 1986) and in uncontrolled surveys (Rosenstock et al. 1986; Andrews 1983). Supporting evidence comes from the New England Deaconness 314 Hospital, where a two-part survey, before and 20 months after the adoption of a strict smoking policy, demonstrated a reduction in the prevalence of smoking among employees from 32 to 24 percent, along with an increase in the prevalence of ex-smokers (27 to 34 percent) (Andrews 1983). However, methodologic problems prevent an un- equivocal conclusion. The first survey included both employees and patients, but the followup covered only employees; smoking rates for employees only are not provided. The survey method was not specified, but it did not appear to be a probability sample, thereby limiting generalizability of the finding to the entire group. Finaliy, because the same group of employees was not surveyed at followup, an alternate interpretation for the change in smoking prevalence is that the policy influenced employee turnover rates so that smokers left and were replaced by ex-smokers. The study did not assess employee turnover. Controlled studies by Biener and colleagues (1986) and Rigotti and colleagues (1986) did not detect an increase in smoking cessation by employees of hospitals that adopted smoking policies. In the study by Rigotti and colleagues, nurses in the policy group did not differ from controls in their motivation to quit, or their expectation of doing so, or in the number or success of quit attempts. The prevalence of smoking in the policy group and in the control group was similar at baseline and did not change in the year after policy adoption. Similarly, employees in a Rhode Island hospital with a smoking policy were no more likely to try to quit or to succeed in quitting than were employees in a control hospital (Biener et al. 1986). The number of smokers in these two studies was small, and it is possible that the studies lacked adequate power to detect changes in behavior. Followup periods of greater than 1 year may also be required. Attitudes About Smoking There has been little assessment of the impact of worksite smoking policies on attitudes about smoking. The two controlled studies of hospital smoking policies assessed attitudes about the health risks of smoking and about involuntary smoking (Biener et al. 1986; Rigotti et al. 1986). There was no significant change in the smokers’ beliefs about the health risks of smoking or about environmental tobacco smoke exposure. Management Issues There is only sketchy evidence about the impact of worksite smoking policies on absenteeism, health care costs, productivity, or employee turnover. No systematic analysis of economic impact has been done. There is an anecdotal report of cost saving by the Merle 315 Norman Cosmetics Company, which reported lower absenteeism and housekeeping costs and increased productivity in the year after it adopted a ban on smoking (ALA of San Diego 1984). In the 6 months after Pacific Northwest Bell adopted a total smoking ban, no employees left because of it (Martin 1986). Rigotti and colleagues (1986) reported no change in employee turnover in the year after the adoption of a hospital smoking ban. Rosenstock and colleagues (1986) found that self-reported work performance was unaffected in 75 percent of employees and improved in 21 percent. Costs involved in implementing a smoking policy have not been systematically mea- sured, but appear from case reports to have been small (BNA 1986). Adverse impacts of worksite smoking policies have not been report- ed. Legislation Restricting Smoking in Public Places Legislation restricting smoking in public places has been less well evaluated than worksite smoking policies. Opinion polls in States and communities that have passed smoking control regulations provide some information on attitudes about smoking and smoking policies. There are no controlled studies of the impact of legislation on smoking behavior or attitudes. Policy Implementation and Enforcement Evaluation of the implementation of State or local smoking control statutes has been limited. In general, enforcement is delegated to a State or local agency, such as the department of public health. Enforcement is handled passively rather than actively; the responsi- ble agency responds to complaints, but does not actively monitor policy compliance by surveying worksites, restaurants, or public places. Nonsmokers rights groups and individual activists are a major force for informing the public and aiding enforcement by bringing complaints (Sandell 1984). The experience of cities like San Francisco and States like Minnesota contradicts tobacco industry estimates of the expense and intrusiveness required to enforce a smoking law (Martin 1986, New York Times 4/13/86; Sandell 1984). In the first year after San Francisco implemented a strict workplace smoking law in March 1984, only 124 complaints were processed and 1 citation was issued; there were no legal actions. No new employees were hired and no additional funds were required for enforcement. Policy enforcement required progressively less of a single employee’s time over a 1-year period (Martin 1986). Minnesota enforces its 1975 State smoking law in a fashion similar to San Francisco’s. State public health depart- ment officials estimate that they handle 1,200 to 1,400 complaints per year, with costs of enforcement estimated to be under $5,000 per 316 year (Sandell 1984). A survey of 10 California cities with workplace smoking laws documented that complaint rates were low and enforcement of these laws was a low priority for all city govern- ments. Officials indicated that they would spend any additional funds available for enforcement on a public education campaign to increase awareness of the law rather than initiate active surveil- lance (Linson 1986). Because active monitoring of policy compliance is not done, a low complaint rate is often taken as evidence of a high compliance rate. Data from Minnesota suggest that this is not always true. In 1976, 1 year after the comprehensive Clean Indoor Air Act was enacted, 43 percent of respondents to a statewide poll felt that the law was not very effective in reducing smoking in public places; 38 percent found it somewhat effective and 12 percent, very effective (Minneapolis Tribune 1976). Six years after the law took effect, a survey of Minnesota businesses with 200 or more employees documented that only 46 percent of businesses had such a policy. Restaurants, however, had nearly uniformly conformed to the law within a year of implementation (Sandell 1984). A statewide opinion poll in 1978 demonstrated that over 70 percent of both smokers and nonsmokers felt that the Clean Indoor Air Act should be strictly enforced (Minneapolis Tribune 1978). Two years later, Minnesotans were of mixed opinion about the law’s enforcement: fewer than half (43 percent) considered it very well enforced, 42 percent felt it was not so well enforced, and 10 percent said it was not enforced at all (Minneapolis Tribune 1980). Randolph (1982) studied factors associated with compliance and enforcement of local ordinances regulating smoking. She assessed the implementation of a recently enacted San Rafael, California, smoking ordinance by interviewing proprietors of randomly selected businesses. Less than 1 year after the ordinance went into effect, 68 percent of 25 proprietors were aware of the policy, but only 44 percent of 30 businesses had complied with the requirement to post no-smoking signs. The major variable associated with compliance by businessmen was the type of business; restaurants, retail food stores, drug stores, banks, and movie theaters were generally posting signs as required, but department stores and small retail stores were not. City residents were less well informed. Fewer than half (45 percent) of 200 randomly selected residents surveyed by telephone were aware of the ordinance, and only 11 percent could describe its provisions. Randolph’s study (1982) of implementation also included a 1980 telephone survey of 600 randomly selected residents of three northern California cities, two with smoking ordinances and one without. Smokers were classified as compliers or noncompliers according to whether they refrained from smoking in supermarkets, 317 which was required by State law. Characteristics of smokers who complied were (1) lower daily cigarette consumption, (2) less per- ceived need to smoke, (3) greater perception of others’ disapproval for tobacco smoking in public, (4) and greater support for policies restricting smoking in public places. Smokers’ perception of pres- sures to refrain from smoking in public, awareness of the presence of a local smoking law, and the duration of the ordinance were not associated with compliance. Enforcement of smoking laws was studied in nonsmokers. The best predictor of enforcement behavior was a nonsmoker’s degree of annoyance with tobacco smoke. Other characteristics associated with enforcement behavior were more negative attitudes about smoking in public places, greater intoler- ance of noncompliance, and higher educational level. Policy Approval National and regional polls have surveyed public opinion about where smoking should be restricted or banned. Regional polls have often been taken when legislation is being considered. There are little data about public opinion on legislation after its enactment. Nationwide public opinion about smoking in public places was assessed by Roper polls in 1976 and 1978 (1978), two Gallup polls (1978, 1983), and the Harris Prevention Index 85 (Harris 1985). The Roper polis asked separate questions about preferences for a smoking restriction or a total ban; the Gallup and Harris polls offered a choice between the two in the same question. In both Roper polls, a majority of respondents favored restricting smoking in all places mentioned: transportation vehicles (airplanes, buses, and trains), restaurants, workplaces, and indoor arenas. By 1978 three- fourths of the respondents favored restrictions in all places except the worksite. Total smoking bans were less popular but still the choice of at least one-fourth of the respondents. The 1983 Gallup poll documented increased public support for smoking restrictions, particularly in restaurants. More than 80 percent of smokers and 90 percent of nonsmokers favored either banning or restricting smoking in airplanes, buses, and trains and restaurants. Over half of both smokers and nonsmokers favored restrictions in motels and at the worksite. Although bans were less popular than restrictions, they were twice as popular with nonsmok- ers as with smokers. In 1985, 80 percent of the respondents to the Harris poll supported restrictions or bans in public places in general. Regional polls generally support the conclusions of nationwide surveys. Minnesota is one State where public opinion of existing legislation has been measured. Five years after enactment, public opinion of Minnesota’s 1975 Clean Indoor Air Act remained high. Ninety-two percent of the 1,200 respondents to a statewide poll favored the act, 318 including 87 percent of heavy smokers (two packs per day) and a larger fraction of lighter smokers (Minneapolis Tribune 1980). During the first year of the San Rafael, California, smoking ordinance, nearly 70 percent of 200 randomly selected residents agreed that there should be laws about smoking in public places and 77 percent said they would have voted for the ordinance had they had the opportunity (Randolph 1982). The reaction of local busi- nesses was less favorable. Over half (52 percent) did not like the ordinance, but only 41 percent favored rescinding it. The most common reason for support was concern for smoking-related damage to property. Concerns about invading personal rights and fear of losing business were the major reasons for opposition. Attitudes and Social Norms It has been suggested that smoking restrictions will alter public attitudes and norms about smoking behavior. There are few data addressing this hypothesis. Randolph (1982) reported on attitudinal differences between residents of California communities with and without smoking ordinances. Smokers in two cities with laws had more negative attitudes about smoking in public places and were more likely to feel that there should be laws regarding tobacco smoking in public. However, there was no difference in smokers’ perceptions of social pressures to refrain from smoking. Nonsmokers in cities with laws were more likely to believe that tobacco smoke should be regulated in public, but they were no more annoyed by tobacco smoke, intolerant of noncompliance, or disapproving of smoking in public places than residents of the city without a law. Although residents of communities with and without smoking ordinances did not differ in their personal support of smoking laws, residents of communities with laws perceived greater support for these laws by other residents of their communities. This cross-sectional study cannot differentiate whether these attitudinal variations were a cause or consequence of differences in community smoking ordinances. Data from opinion polls demonstrate that negative attitudes about smoking generally preceded rather than followed legislation to restrict smoking in public places. The four Adult Use of Tobacco Surveys, a series of nationwide surveys conducted between 1964 and 1975, measured attitudes in the decade after the health hazards of smoking were first widely appreciated (US DHEW 1969, 1973, 1976). As early as the first survey in 1964, a majority of nonsmokers agreed with these statements: “It is annoying to be near a person who is smoking cigarettes” and “Smoking should be allowed in fewer places than it is now.” By 1970, a majority of all respondents agreed with these statements. By 1975, a majority of smokers agreed with the idea of further restricting smoking, suggesting that there was wide 319 public support for restricting smoking well before the first compre- hensive Clean Indoor Air Act was passed in Minnesota in 1975. As early as 1973, 73 percent of the nonsmokers in a Minnesota poll felt that they had the right to a smoke-free environment, and 65 percent wanted to ask others not to smoke (Minneapolis Tribune 1973). More recent opinion polls document that negative attitudes about smoking in public continue to grow. In a 1985 Gallup poll, 75 percent of the respondents (including 62 percent of the smokers) felt that smokers should refrain from smoking in the presence of nonsmokers. However, nonsmokers’ attitudes do not translate directly into action. A smaller proportion of nonsmokers are willing to confront a smoker whose smoke is bothersome. In three successive Roper polls between 1974 and 1978, fewer than 10 percent of the nonsmokers indicated that they would ask an individual smoking indoors to stop (Roper 1978). Only 32 percent of the nonsmokers in a 1974 Minnesota poll would complain when bothered by another person’s smoking, although an additional 31 percent would take nonconfron- tational action such as moving away or opening windows (Minneapo- lis Tribune 1974). These data suggest that in the mid-1970s, despite strong preferences, many nonsmokers did not perceive that asking a smoker to stop was socially sanctioned behavior. Smokers, on the other hand, report an awareness of nonsmokers’ concerns and a willingness to comply with restrictions. Over 90 percent of the smokers in a 1981 Iowa poll (Des Moines Register 1981) extinguished tobacco when they saw a no-smoking sign. Sixty percent of the smokers in a 1973 Minnesota poll (Minneapolis Tribune 1973) had at least some misgivings about smoking in the presence of nonsmokers, and 90 percent would not have been offended if asked not to smoke. Only 29 to 36 percent of smokers in three Roper polls (1974-1978) lit a cigarette without looking around, asking others, or refraining from smoking (Roper 1978). There may be, therefore, an interaction between attitudes and policy development. These survey data suggest that attitudes about smoking in public preceded and may have contributed to the development of a public poficy (Breslow 1982). At the same time, publicity surrounding campaigns for legislation may increase public awareness of an issue such as the hazards of involuntary smoking and therefore contribute to further changing attitudes. Smoking Behavior The impact of legislation on smoking behavior has received little formal attention. There are no controlled studies in which smoking behavior has been tracked over time in the States or communities that have enacted smoking legislation. In Randolph’s one-time assessment (1982) of smoking behavior in California communities with and without smoking control ordinances, there was no differ- 320 ence in smoking prevalence or mean daily cigarette consumption between the residents of a city with a recent ordinance and one without. A lower prevalence of smoking in one community with a longstanding ordinance was probably explained by demographic differences between that community and the other areas. Uncontrolled reports of declining smoking prevalence or cigarette consumption in a State or community with a smoking law cannot establish a causal relationship. This was particularly the case during the 1970s, when both smoking prevalence and per capita cigarette consumption were declining nationally. Warner (1981a; Warner and Murt 1982) conducted a series of analyses of this decline. In separate analyses, he estimated the levels of smoking prevalence and ciga- rette consumption that would have been achieved if previous trends in these indicators had continued unabated through the 1960s and 1970s. Cigarette consumption in 1978, for example, would have been 36 to 41 percent higher had previous patterns continued. He ascribed the difference between observed and modeled values to the impact of the so-called antismoking campaign, defined as the combination of public events, legislative activity, and Federal regulations that affected cigarette price, counter-advertising, and the circumstances in which smoking was allowed. To assess the relative contributions of components of the anti- smoking campaign to the decline in adult per capita cigarette consumption, Warner (1981a) developed a multivariate analysis that included independent variables to account for price fluctuations, adverse publicity about smoking, antismoking activities, and the effectiveness of the nonsmokers’ rights movement. The percentage of adults residing in States restricting smoking in public places was used as an index of the strength of the nonsmokers’ rights movement. This variable was strongly associated (p< 0.0001) with decreases in consumption from 1973 to 1978. In Warner’s view, the temporal relationship between the growth in legislation restricting smoking in public places and the decline in cigarette consumption is so close that a causal relationship is unlikely. He attributed the decline in consumption to the changes in attitudes and social norms about smoking that were an earlier consequence of the entire antismoking campaign. He regarded the legislation as another reflection of changing social norms rather than the creator of them (Warner 1981b). Recommendations for Research Policies restricting the circumstances in which smoking is permit- ted have been adopted by a broad range of institutions, mostly in the last decade. Smoking regulations affect the daily lives of a large and growing number of Americans. Consequently, these policies are of 321 interest to many individuals and groups. For instance, public health officials are concerned about the health effects of both active and involuntary smoking; they are most interested in whether these policies actually reduce a population’s exposure to environmental tobacco smoke and whether they will alter the prevalence of smoking. Behavioral scientists, primarily concerned with smoking behavior and attitudes, are chiefly interested in how smoking policies alter these variables and how this knowledge can increase our understanding of the dynamics of smoking behavior. Businesses, unions, and government policymakers have different perspectives. They are faced with deciding whether to adopt smoking restrictions and how to improve the implementation and acceptability of existing ones. Information about the determinants of policy approval and compliance will be of most interest to them. Businesses may also be concerned about the economic and managerial impacts of smoking restrictions. Understanding the effect of policies on smoking behavior is of widest interest and deserves attention. Policies may affect the natural history of smoking behavior at several points, and detailed behavioral information should be collected to distinguish among effects on rates of initiation, cessation, and relapse. Studying how smokers cope with enforced abstinence may provide additional insights into the maintenance of smoking behavior. Detailed studies of the influence of policy may advance the state of knowledge about the determinants of smoking behavior in general. The relationship between interventions at the social and individual levels is also of interest. Researchers should consider whether the effectiveness of individual treatment is enhanced by the presence of a smoking policy, and whether the impact of a policy is enhanced by the availability of individual treatment. Concurrent collection of infor- mation on attitudes about smoking may help to clarify the nature of the relationships among attitudes, smoking behavior, and smoking policies. In addition to considering a variety of outcome measures, re- searchers should address the determinants of these outcomes. Characteristics of the policy, the institution, and the population should be considered. The components of a smoking policy and its implementation (such as restrictiveness, degree of advance notice, degree of support for the policy by affected groups, access to smoking cessation programs) that contribute to its effect—be it on behavior, attitudes, air quality, acceptability, or compliance—have generally not been analyzed. Because smoking policies vary widely in their provisions and implementation, they cannot be evaluated as a unitary intervention; i.e., better operationalization of “policy” inter- ventions is needed. The relative strength of policy components on each outcome measure should be assessed in order to make informed 322 policy recommendations. For example, the degree of protection from involuntary smoke exposure afforded by policies of different degrees of stringency in not empirically known. To acquire this knowledge, researchers will need to develop and validate measures of such concepts as restrictiveness. The index described in the appendix to this chapter is a preliminary attempt to do that. The components of a policy that are most powerful in reducing cigarette consumption, inducing cessation attempts, preventing relapse, or reducing smok- ing initiation need to be identified. Similarly, the components of a policy associated with maximal acceptability and compliance have been addressed only cursorily. Dawley and colleagues (Dawley, Morrison et al. 1981; Dawley and Burton 1985), for example, have examined variables such as the wording of signs or the presence of active enforcement. Guidelines for the implementation of smoking policies have not been experi- mentally derived. Research could empirically support or refute recommendations on the basis of experience. Interventions such as the training of managers to handle implementation problems might then be developed to increase policy acceptability and compliance. Different types of organizations have presented different climates for the adoption of smoking regulations. In assessing policy impact, there may also be substantial interactions between the policy and type of facility in which it is adopted. Even within a single type of facility, there may be considerable variability in social norms, social supports, and characteristics of the population using it. Sorensen and colleagues (1986) have pointed out these differences among worksites. Policy evaluations should consider these variables. Because smoking policies represent a recent social phenomenon, there is at present relatively little information about their impact. New policies are being adopted at a growing rate, providing researchers with the opportunity to study natural experiments that, up to now, have largely gone unevaluated. The variety of potential outcomes, number of interested parties, and current lack of informa- tion make efforts to collect systematic data on new public and private sector smoking policies a high priority for research. Con- trolled studies are desirable and permit the firmest conclusions, but with the current knowledge base, even limited efforts may yield valuable information. Uncontrolled case studies, for example, can provide suggestive data and generate hypotheses for further testing. In some cases, data are already partially collected. For example, many businesses considering smoking policies survey employees at baseline, but few repeat the survey after policy adoption. At the aggregate level, it may be possible to estimate the impact of legislation on smoking prevalence or cigarette consumption by relating national survey data on smoking behavior to smoking restrictions in geographic areas. 323 Conclusions 324 1. Beginning in the 1970s, an increasing number of public and private sector institutions have adopted policies to protect individuals from environmental tobacco smoke exposure by restricting the circumstances under which smoking is permit- ted 2.Smoking in public places has been regulated primarily by government actions, which have occurred at Federal, State, and local levels. All but nine States have enacted laws regulating smoking in at least one public place. Since the mid- 1970s, there has been an increase in the rate of enactment and in the comprehensiveness of State legislation. Local govern- ments have enacted smoking ordinances at an increasing rate since 1980; more than 80 cities and counties have smoking laws in effect. . Smoking at the workplace is regulated by a combination of government action and private initiative. Legislation in 12 States regulates smoking by government employees, and 9 States and over 70 communities regulate smoking in the private sector workplace. Approximately 35 percent of busi- nesses have adopted smoking policies. The increase in work- place smoking policies has been a trend of the 1980s. . Smoking policies may have multiple effects. In addition to reducing environmental tobacco smoke exposure, they may alter smoking behavior and public attitudes about tobacco use. Over time, this may contribute to a reduction of smoking in the United States. To the present, there has been relatively little systematic evaluation of policies restricting smoking in public places or at the workplace. 5. On the basis of case reports and a small number of systematic studies, it appears that workplace smoking policies improve air quality, are met with good compliance, and are well accepted by both smokers and nonsmokers. Policies appear to be followed by a decrease in smokers’ cigarette consumption at work and an increase in enrollment in company-sponsored smoking cessation programs. . Laws restricting smoking in public places have been imple- mented with few problems and at little cost to State and local government. Their impact on smoking behavior and attitudes has not yet been evaluated. . Public opinion polls document strong and growing support for restricting or banning smoking in a wide range of public places. Changes in attitudes about smoking in public appear to have preceded legislation, but the interrelationship of smoking attitudes, behavior, and legislation are complex. APPENDIX APPENDIX The Comprehensiveness index of State Laws To permit comparisons over time, an index of the comprehen- siveness of each State’s smoking law was created. Laws were classified on the basis of the number and nature of places where smoking was restricted or prohibited. The overall principle was that stronger measures are those that reduce exposure to ETS to the greatest degree. More comprehensive laws were considered to be those that restrict smoking in a larger number of public places, extend to privately owned facilities, and cover places where individu- als spend a large amount of time. Laws regulating smoking in private worksites were considered to be the the most comprehensive, and States with such laws were assigned the extensive category. Because individuals spend more time at work than in any other place outside the home, worksite legislation has the potential for marked reductions in public exposure to involuntary smoking. Worksite laws also represent an extension of legislation to the private sector, considered a further evidence of their comprehensiveness. Nine States are categorized as having extensive restrictions; the average number of public places covered by their legislation was 11.0. The next most stringent category, moderate, was assigned to States that regulated smoking in restaurants. Restaurants were chosen because they represent privately owned public places and because laws covering them have been controversial to enact. It was felt that States regulating restaurants but not the private workplace had moderately comprehensive restrictions. The 10 States in this category also regulated smoking in a large number of public places (9.5). The last two categories, nominal and basic, were defined for States that did not regulate smoking in restaurants or in the private workplace. They differed in the number of public places covered. States restricting smoking in one to three public places were considered to have nominal restrictions. Those restricting smoking in four or more public places were classified as basic. 327 This number of public places covered by smoking restrictions increases with increasing comprehensiveness of categories. Category Extensive Moderate Basic Nominal No policy Mean number of Number of public places States covered 9 11.0 10 9.5 15 6.6 8 1.4 9 0 For the calculation of the comprehensiveness index, categories were weighted as follows: 328 Category Extensive Moderate Basic Nominal No policy Weight 1.00 75 50 25 .00 References ACTION ON SMOKING AND HEALTH. Statewide No Smoking Laws Enacted by State Legislatures. Washington, D.C., Action on Smoking and Health, 1986. ADDISON, R. New England Baptist Hospital Project, 1983-1984. Boston, Clean Indoor Air Educational Foundation, September 1984. AMA COUNCIL ON SCIENTIFIC AFFAIRS. Nonsmoking i in hospitals. Connecticut Medicine 48(5):297-305, May 1984. AMERICAN ACADEMY OF PEDIATRICS, COMMITTEE ON ENVIRONMENTAL HAZARDS. Involuntary smoking: A hazard to children. Pediatrics 77(5):755-757, May 1986. AMERICAN COLLEGE OF PHYSICIANS. Cigarette Abuse Epidemic. (unpublished position paper). January 28, 1986. AMERICAN HOSPITAL ASSOCIATION. 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U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, 1964. VETTEL, P. The don’t butt inn: Hotels now cater to nonsmokers. Chicago Tribune, February 23, 1986. WALSH, D.C. Corporate smoking policies: A review and an analysis. Journal of Occupational Medicine 26(1):17-22, January 1984. WALSH, D.C., GORDON, N.P. Legal approaches to smoking deterrence. Annual Review of Public Health 7:127-149, 1986. WARNER, K.E. Cigarette smoking in the 1970’s: The impact of the antismoking campaign on consumption. Science 211(4483):729-731, February 13, 1981a. WARNER, K.E. State legislation on smoking and health: A comparison of two policies. Policy Sciences 13:139-152, 1981b. WARNER, K.E. Regional differences in State legislation on cigarette smoking. Texas Business Review 56(1):27-29, January-February 1982. WARNER, K.E., ERNSTER, V.L., HOLBROOK, J.H., LEWIT, E.M., PERTSCHUK, M., STEINFELD, J.L., WHELAN, E.M. Public policy on smoking and health: Toward a smoke-free generation by the year 2000. Circulation 73(2):381A-395A, February 1986. WARNER, K.E., MURT, H.A. Impact of the antismoking campaign on smoking prevalence: A cohort analysis. Journal of Public Health Policy 3(4):374—-390, December 1982. WEIS, W.L. Can you afford to hire smokers? Personnel Administrator 26(5):71-78, May 1981. WINDSOR, R.A., BARTLETT, E.E. Employee self-help smoking cessation programs: A review of the literature. Health Education Quarterly 11(4):349-359, Winter 1984. ZIADY, M. A smoke-free workplace: Clearing the air at Pacific Northwest Bell. Good Health, Good Business (1):1, 1986. 334 INDEX Environmental Tobacco Smoke is abbreviated as ETS throughout this index. ABSORPTION biological markers for ETS, 200— 206 biological markers of smoke absorp- tion in smokers and nonsmokers, 181 ETS vs. active smoking, compari- son, 215-216 nicotine, tobacco smoke exposure determination, 203-205 ACROLEIN measurement under realistic condi- tions (table), 148 ADOLESCENTS regulations in schools to prevent smoking initiation, 282 AEROSOLS mainstream smoke, particle size measurement during laboratory smoking, 182-183, 186 monodisperse vs. polydisperse, af- fect on respiratory tract deposi- tion, 181-182 regional deposition in respiratory tract, smoke particle size as fac- tor, 189, 191-192 sidestream smoke, mass median di- ameter effect on deposition in respiratory tract, 187 AGE FACTORS respiratory effects of involuntary smoking in infants and children, 42-44 AIR POLLUTION (See also ENVIRONMENTAL TO- BACCO SMOKE) hospital smoking policies, assess- ment of effect, 311 ALDEHYDES irritant in ETS, 229 AMMONIA irritant in ETS, 229 AROMATIC AMINES sidestream smoke levels higher than in mainstream smoke, 14 AROMATIC HYDROCARBONS measurement under realistic condi- tions (table), 149-150 ASTHMA (See also RESPIRATORY TRACT DISEASES) children, maternal smoking as risk factor, 55-58 pulmonary function in adult asth- matics exposed to cigarette smoke, 63, 65 ATTITUDES public attitudes and social norms, cigarette consumption relation- ship, 321 public knowledge and attitudes about smoking, assessment by surveys, 307 public toward smoking, conclusions of 1986 report, 324 review of impact of smoking re- strictions, 319-320 smokers on cessation or reduction, restrictions and social norms as factors, 305 BEHAVIOR, HUMAN (See also SMOKING CHARACTER- ISTICS; SMOKING HABIT) anticipated changes by smokers to workplace regulations, 312 assessment of impact of smoking policies on smokers, 307 335 INDEX BEHAVIOR, HUMAN—Contd. bans on smoking, effect on behav- ior of smokers, 16 direct and indirect effects of smok- ing policies, 304 hospital employees, smoking behav- ior before and after policy im- plementation, 315 hospital patients and employees, current evidence of smoking pol- icies, 308-309 nonsmoking as normative behavior, reinforcement with smoking poli- cies, 304 reduction or cessation of smoking, indirect effect of smoking poli- cies, 304-305 research recommendations, effect of smoking restrictions, 322 review of impact of smoking re- strictions, 320-321 smoking policy impact, evaluation, 306 BIOASSAY chemical assays for human expo- sure to cigarette tar components, 206, 217 cotinine levels as measure of nic- otine absorption, 205-206 nicotine in blood for exposure de- termination, feasibility, 205 BIRTH WEIGHT maternal smoking as risk factor, 6 BLOOD cotinine level as marker for ETS exposure in nonsmokers, 36 cotinine levels as measure of nic- otine absorption in nonsmokers, 205-206 cotinine levels in ETS-exposed non- smokers vs. active smokers (ta- ble), 211-214 nicotine and cotinine levels to quantify ETS exposure, 208 nicotine levels in ETS-exposed non- smokers vs. active smokers (ta- ble), 209-210 nicotine levels in nonsmokers vs. smokers, 216 white blood cell counts in smokers vs. nonsmokers, 244 336 BRAIN CANCER (See also CANCER } ETS exposure as risk factor, 102, 104 BREAST CANCER (See also CANCER ) spousal smoking as risk factor, 102 BRONCHITIS (See also RESPIRATORY TRACT DISEASES) children, involuntary smoking rela- tionship, longitudinal studies, 38, 42 children of smokers, conclusions about risk, 106 infants and children, parental smoking as risk factor, 10 CANCER (See also BRAIN CANCER; BREAST CANCER; CERVICAL CANCER; LUNG CANCER; RES- PIRATORY TRACT CANCER) carcinogenesis, initiators and pro- moters in tobacco smoke, 28 carcinogens in ETS as risk factors, 135 children, parental smoking as risk factor for cancers other than lung cancer, 102-105 ETS exposure risk, 102-104 involuntary smoking relationship requires further investigation, 14 smoking as major risk factor, 6 CARBON MONOXIDE acute toxicity in animals as factor in smoke carcinogenicity testing, 247 biological marker for ETS absorp- tion, 201-202 ETS exposure measurement, lack of specificity as limitation, 202 involuntary smoking exposure may be more constant than active smoking, 202 lung deposition kinetics as factor in temporal variation in concen- tration, 201-202 measurement under realistic condi- tions (table), 151-154 sidestream smoke vs. mainstream smoke, 129 INDEX CARBON MONOXIDE—Contd. workplace level, contribution of to- bacco smoke, 232 CARBOXYHEMOGLOBIN LEVELS biological marker for carbon mon- oxide exposure, 202 CARCINOGENESIS initiators and promoters of cancer in tobacco smoke, 28 tumor induction in animal tissues with cigarette smoke condensate, 249-250 CARCINOGENS environmental vs. mainstream smoke, 134-135, 137 ETS vs. mainstream smoke in in- door environments (table), 136 human and animal, definition, 135, 137 mainstream and sidestream smoke, 23-24 sidestream and ETS, 251-252 CARDIOVASCULAR DISEASES ETS exposure as factor not estab- lished, 10-11 involuntary smoking as risk factor, conclusions, 107-108 involuntary smoking relationship requires further investigation, 14 nonsmokers, prospective and case- control studies, 105-106 CASE-CONTROL STUDIES (See also EPIDEMIOLOGICAL STUDIES) cardiovascular disease risk, 105-106 lung cancer risk, 97-98 lung cancer risk in exposed non- smokers, Hong Kong study, 80- 81 lung cancer risk in spouses of smokers, Louisiana study, 79-80 lung cancer risk in wives of smok- ers, Greek study, 78-79 lung cancer risk relationship, Four Hospitals study, 84-86 lung cancer risk relationship, Ger- man study, 90 lung cancer risk relationship, Japa- nese study, 88-89 lung cancer risk relationship, Swedish study, 89-90 CASE-CONTROL STUDIES lung cancer risk relationship, Unit- ed Kingdom study, 86-88 respiratory disease risk in children, 43-44 CELLS inflammatory cell number and function in smokers, inferences for involuntary smokers, 244-245 inflammatory, experimental models of cigarette smoke inhalation, 245-246 inflammatory, need to determine effect of ETS exposure, 252 CELLS, EPITHELIAL chronic ETS exposure, inferred risk in nonsmokers, 240-241 ETS exposure effect, research need- ed, 252 hyperplasia, loss of cilia, nuclear atypia, smoking habit relation- ship, 239-240 CERVICAL CANCER (See also CANCER) spousal smoking as risk factor, 102 CESSATION OF SMOKING public attitudes and smoking poli- cies as indirect influences, 304— 305 research recommendations on effect of smoking restrictions, 322 workplace programs as part of smoking control, 297 workplace programs, survey data, 294 workplace smokers motivation and success, smoking policies as fac- tor, 313-315 CESSATION OF SMOKING, METHODS workplace program, smoking policy implementation effect on partici- pation, 314-315 CHEMICAL ANALYSIS sidestream vs. mainstream smoke, 127 CHILDREN asthma, maternal smoking as risk factor, 55-58 brain tumors, maternal smoking as factor, 104 337 INDEX CHILDREN—Contd. bronchitis, involuntary smoking re- lationship, longitudinal studies, 38, 42 cancer risk other than lung cancer, parental smoking as risk factor, 102-105 cough, phlegm, and wheezing, pa- rental smoking as risk factor, 44, 47-49 ETS exposure, determinants, 12 ETS exposure, reported irritation, 239 health risks of ETS exposure, con- clusions, 107 health risks of involuntary smok- ing, summary and conclusions of 1986 report, 12-13 leukemia, maternal smoking during pregnancy as factor, 103 lung cancer risk, parental smoking as factor, 90-91 lung function, information needed on relationship with ETS expo- sure, 32 lung function, involuntary smoking risk relationship (table), 50-52 lung function, maternal smoking relationship, 49, 53-54 lung function, parental smoking as factor, 13, 107 middle ear effusions and diseases, parental smoking risk relation- ship, 58-59 respiratory diseases, involuntary smoking relationship (table), 39- 41 respiratory diseases, parental smok- ing as risk factor, 10, 13, 43-44 respiratory function tests, maternal smoking as factor, 53 respiratory symptoms in children of smokers, 13 respiratory symptoms, relationship with involuntary smoke exposure (table), 4546 respiratory system effects of invol- untary smoking, 37-59 saliva cotinine concentrations, in- fluence of parental smoking, 207-208 338 CIGARETTE EQUIVALENTS calculation of individual constitu- ents needed to determine disease risk, 199-200 involuntary smoking toxicity esti- mation, mathematical modeling, 198-200 CIGARETTE SMOKE (See also ENVIRONMENTAL TO- BACCO SMOKE; MAINSTREAM SMOKE; SIDESTREAM SMOKE; SMOKE STREAMS; TOBACCO SMOKE) aerosol, suspension of particles in a gaseous or vapor medium, 181 animal models of carcinogenicity, 247-249 carcinogenicity, condensate bioassay as alternative to smoke expo- sure, 249-250 carcinogenicity demonstrated in an- imal models, 252 carcinogenicity testing in animals, nicotine and carbon monoxide toxicity as factor, 247 ETS in public places, major source, 128 inflammatory cell function, experi- mental models of inhalation ef- fect, 245-246 particulate mass deposited in respi- ratory tract, 193, 198 particulate phase constituents, side- stream to mainstream ratio (ta- ble), 130-131 regional deposition in respiratory tract, particle size as factor, 189, 191-192 total suspended particulates gener- ated under laboratory conditions (table), 197 toxic and carcinogenic agents in in- door environments (table), 136 unfiltered cigarette, comparison of mainstream and sidestream smoke (table), 128 vapor phase constituents, side- stream to mainstream ratio (ta- ble), 130-131 CIGARETTES nonfiltered, vapor and particulate phase smoke components (table), 130-131 INDEX COMBUSTION TEMPERATURE mainstream and sidestream smoke, effect on composition, 24 sidestream vs. mainstream smoke generation, effect on component levels, 128-129 COTININE biological marker for ETS absorp- tion, 35-36, 200 blood levels in nicotine-injected vs. smoke-exposed nonsmokers, 215- 216 body fluid level as marker for smoke exposure in nonsmokers, 8 body fluid levels in nonsmokers as measure of nicotine absorption, 205 body fluid levels in nonsmokers to establish lung cancer risk, 95 body fluid levels increase with re- ported ETS exposure, 15, 217 ETS exposure marker of choice in epidemiological studies, 217 ETS exposure marker under real- life conditions, 207 ETS exposure quantification, 208, 215 nicotine absorption estimation, 205- 206 plasma, urine, saliva concentra- tions, correlation, 205 plasma, urine, saliva levels in ETS- exposed nonsmokers vs. active smokers, 211-214 urinary levels in ETS-exposed vs. nonexposed men, 207 COUGH (See also RESPIRATORY SYMP- TOMS) children of parents who smoke, re- lationship, 44, 47-49 EARS middle ear effusions in children of smokers, 58-59, 107 EMPHYSEMA (See also RESPIRATORY TRACT DISEASES) nonsmokers vs. smokers, 246 ENVIRONMENTAL TOBACCO SMOKE (See also CIGARETTE SMOKE; IN- VOLUNTARY SMOKING; MAINSTREAM SMOKE; SIDE- STREAM SMOKE; TOBACCO SMOKE) absorption of constituents by non- smokers under experimental! and natural exposure, 206-207 active smoking dose-response rela- tionships provide insight into risks, 26-28 acute exposure, irritation effects, 229-239 acute physiological response, exper- imental studies, 233-239 air dilution effect on particle size and distribution, 134 airways hyperresponsiveness and other factors in response, 28 annoying and irritating effects of exposure, field and experimental studies, 231-239 assessment techniques needed of recent and remote exposure, 14 atmospheric markers of exposure, 33 atmospheric vs. biological markers of absorption, 201 bioassays needed to determine gen- otoxicity, 252 biochemical markers of exposure during experimental and natural conditions, 206-207 biological markers for absorption, 200-206 biological markers for estimating exposure, 141 brain cancer risk relationship, 102, 104 cancers other than lung cancer, risk relationship, 102-104 carbon monoxide as biological marker of exposure, 201-202 carcinogen levels vs. mainstream smoke, 134-135, 137 carcinogenicity, 10 carcinogenicity, in vivo and in vi- tro experimental determination, 247-251 339 INDEX ENVIRONMENTAL TOBACCO SMOKE—Contd. cardiovascular disease risk, prospec- tive and case-control studies, 105-106 chemical analysis shows spectrum of carcinogens, 251-252 chemical composition, comparison with mainstream smoke, 135, 137 chemical composition, complexity as factor in exposure determina- tion, 147 chronic exposure, inferred risk for respiratory epithelial changes, 240-241 cigarettes as major source in public places, 128 concentration determination, venti- lation and other factors, 146- 147, 164-165 concentration measurement, 193 concentrations in public transporta- tion as factor in smoking restric- tions, 278 constituents from mainstream and sidestream smoke, 7-8 contribution to indoor air pollution, conclusions, 169 cotinine as biological marker of ab- sorption, 35-36 cotinine as exposure marker of choice in epidemiological studies, 217 cumulative, duration, and intensity of exposure influences effects, 33 determinants of exposure, 11-12 disease risk estimation, value of bi- ological markers of absorption, 200-201 dose, product of mass in inhaled air and deposition fraction, 193 exposure estimation, mathematical model using “cigarette equiva- lents”, 198-200 exposure expressed as ciga- rettes/day, variations in esti- mates, 25-26 exposure, extrapolation of active smoking data, 23-28 eye irritation in exposed children, 239 eye, nose, throat, respiratory sys- tem irritation, conclusions, 252 340 ENVIRONMENTAL TOBACCO SMOKE—Contd. genotoxic potential, use of short- term in vitro assays, 250-251 health effects, 21-106 health effects, methodological prob- lems in assessment, 21-22 health effects of exposure, summa- ry, 13-14 health risk determination, assess- ment of exposure critical, 32 health risks of exposure, conclu- sions, 7, 107-108 human exposure, factors in estima- tion, 139, 141-142 “individual solution” approach to workplace smoking implies no hazard, 298 inflammatory cell functions in smokers, inferences for exposed nonsmokers, 244-245 irritant components, whole side- stream smoke vs. gas phase only, 236-238 irritant effect on allergic persons, 239 irritant effects of exposure in non- smokers in restaurants and of- fices, 232 laboratory, toxicological, human ex- posure, and epidemiological in- vestigations of hazards, 22-23 lung cancer risk, epidemiological and case-control evidence, 97-98 lung cancer risk in exposed non- smokers, Hong Kong case—con- trol study, 80-81 lung cancer risk in spouses of smokers, Louisiana case-control study, 79-80 lung cancer risk in spouses of smokers, Scottish study, 77-78 lung cancer risk in wives of smok- ers, Greek case-control study, 78-79 lung cancer risk, need for more ac- curate estimates of exposure, 102 lung cancer risk relationship, Four Hospitals case-control study, 84— 86 lung cancer risk relationship, Ger- man case-control study, 90 lung cancer risk relationship in nonsmokers, 8-10 INDEX ENVIRONMENTAL TOBACCO ENVIRONMENTAL TOBACCO SMOKE—Contd. lung cancer risk relationship, Japa- nese case-control study, 88-89 lung cancer risk relationship, Los Angeles County study, 83 lung cancer risk relationship, pre- liminary findings of U.S. study, 82 lung cancer risk relationship, sum- mary and conclusions, 96-102 lung cancer risk relationship, Swedish case-control study, 89- 90 lung cancer risk relationship, Unit- ed Kingdom case-control study, 86-88 lung disease risk in nonsmokers as extrapolation of risk in smokers, 30-31 lung effects, inferences from avail- able data, 246-247 lung function effects in nonsmok- ers, 60, 62 lung function in children, more in- formation needed on relation- ship, 32 major irritants, concentrations in mainstream and sidestream smoke (table), 230 mass deposition in respiratory tract estimation, 193, 198 mathematical models of lung can- cer risk in nonsmokers, 93-96 measureable exposure in general population of developed coun- tries, 216 misclassification of smoking status and exposure as factor in deter- mining risk, 66-67, 72-73 monitoring methods to estimate ex- posure, 164-167 nasal vs. mouth inhalation, effect on particle deposition, 189 nicotine and cotinine in body fluids increase with increasing expo- sure, 15 nicotine and cotinine to quantify exposure, 208, 215 nicotine as biological marker of ex- posure, 202-205 nicotine as tracer, need for proper validation in personal monitor- ing, 168 SMOKE—Contd. nicotine levels in nonsmokers may underestimate exposure to other components, 216 organic gases and aromatic com- pounds as indicators of exposure, nonspecificity, 168-169 particle size as factor in dispersion, 169 particle size distribution and breathing pattern effect on dose, 25 particle size facilitates rapid distri- bution, 14 particles, number and size distribu- tion, 137, 139 particulates, aldehydes, phenol, am- monia, and other irritants, 229 personal monitors to measure con- centrations preferable to area monitoring, 166 physiochemical nature, distribution, and estimation of human expo- sure, 125-169 plasma and urine nicotine levels in nonsmokers vs. intravenous nic- otine injection, 215 plasma, urine, saliva cotinine in exposed nonsmokers vs. active smokers (table), 211-214 plasma, urine, saliva nicotine in exposed nonsmokers vs. active smokers (table), 209-210 proximity to smoke source as expo- sure factor, 141 questionnaires for estimating expo- sure, uses and limitations, 34-35 radioactivity, 134 reduction of exposure as primary goal of smoking regulation in public places, 304 respirable suspended particulates in exposed vs. nonexposed nonsmok- ers, 169 respiratory disease risk relationship in infants, children, adults, 10 respiratory infections in infants, risk relationship, 31 respiratory symptoms in nonsmok- ers, possible relationship, 31 school smoking regulations tradi- tionally not to reduce exposure, 282 341 INDEX ENVIRONMENTAL TOBACCO SMOKE—Contd. sidestream smoke as major contrib- utor, 186 statistical significance testing of health risks, 36-37 summary and conclusions of 1986 report, 12-13 temporal and spatial distribution of smokers in exposure determina- tion, 145-146 thiocyanates as biological marker of exposure, 202-203 time-activity patterns as determi- nant of exposure, 142-145 time period most important deter- minant of personal exposure, 167 total suspended particulates in in- door working and living areas (table), 194-196 toxic and carcinogenic agents in- doors from nonfilter cigarettes (table), 136 toxicity, acute irritant effects, and carcinogenicity, 15 urinary cotinine levels in exposed vs. nonexposed men, 207 vapor phase, retention by involun- tary smokers, 126-127 workplace exposure, evidence of health hazards as factor in smoking regulations, 286 workplace, lung cancer risk in non- smokers, 91-92 ENZYME ACTIVITY lungs of smokers, alveolar macro- phages influence on protease-an- tiprotease balance, 242-243 polymorphonuclear elastase in lungs of smokers, 243 respiratory system of smoke-ex- posed animals, 245-246 ENZYMES elastase, 243 EPIDEMIOLOGICAL STUDIES (See also CASE-CONTROL STUD- TES) confounding variables, 36 lung cancer risk in spouses of smokers, 98, 101 methodological considerations, 32- 37 342 EPIDEMIOLOGICAL STUDIES—Contd. questionnaires for estimating ETS exposure, uses and limitations, 34-35 ETS See ENVIRONMENTAL TO- BACCO SMOKE EX-SMOKERS (See also NONSMOKERS) misclassification of status and ETS exposure as factors in determin- ing risks, 66-67, 72-73 EYES annoying and irritating effects of ETS exposure, 231-239 irritation from ETS exposure, 11 irritation in ETS-exposed children, 239 nonsmokers, irritant effect of invol- untary smoking in restaurants and offices, 232 nonsmokers, sidestream smoke as irritant in laboratory, ventilation as factor, 234-235 smoke concentration vs. exposure duration as factors in irritation, 235 tear film in ETS-exposed nonsmok- ers, experimental study, 234 FETUS maternal smoking, effect of expo- sure to tobacco smoke constitu- ents, 31-32 GAS PHASE, CIGARETTE SMOKE activity in in vitro assays, 251 irritation in nonsmokers vs. whole sidestream smoke, 236-238 HOSPITALS (See also PUBLIC PLACES) air quality, effect of smoking poli- cies, 311 cessation of smoking programs, ef- fect, 314-315 employee attitudes and approval of smoking policies, 311-312, 315 lung cancer case-control study in four hospitals, 84-86 smoking policies, positively worded signs and enforcement factors in compliance, 310 smoking policies, review of current evidence on impact, 308-309 INDEX HOSPITALS—Contd. State legislation restricting smok- ing, 269 IMMUNE SYSTEM cigarette smoking effects, 244 INFANTS respiratory diseases, parental smok- ing as risk factor, 10 respiratory system effects of invol- untary smoking, 38-59 time-location patterns, 144 tracheobronchial smoke particle de- position, mathematica! model prediction, 192 INVOLUNTARY SMOKING (See also ENVIRONMENTAL TO- BACCO SMOKE; NONSMOK- ERS) absorption vs. active smoking, 215- 216 absorption of constituents under experimental and natural expo- sure, 206-207 adult asthmatics, lung function ef- fects, 63, 65 allergic persons, irritant effect, 239 assessment of nonsmoker’s expo- sure, 307 atmospheric vs. biological markers of ETS absorption in disease risk estimation, 200-201 bronchoconstriction and asthma in children of parents who smoke, 55-58 bronchoconstriction in normal adult nonsmokers, 63 cancers other than lung cancer, risk relationship, 102-104 carbon monoxide as biological marker of ETS exposure, 201- 202 cardiovascular disease risk, prospec- tive and case-control studies, 105-106 children, brain cancer risk, 104 children, lung function effects (ta- ble), 50-52 children, nonuniform deposition of particles in respiratory disease risk, 192 children, parental smoking as fac- tor in saliva cotinine concentra- tions, 207-208 INVOLUNTARY SMOKING—Contd. children, reported eye irritation, 239 children, respiratory disease rela- tionship (table), 39-41 children, respiratory symptoms re- lationship (table), 45-46 children, respiratory symptoms risk, 44, 47-49 children, risk of cancer other than lung cancer, 102-104 cotinine in body fluids as measure of nicotine absorption, 205 cotinine level in saliva, blood, and urine as ETS exposure marker, 36 cumulative, duration, and intensity influences health risks, 33 disease risk estimation, value of bi- ological markers of ETS absorp- tion, 200-201 ETS vapor phase components, re- tention, 126-127 exposure to sidestream and main- stream smoke components, 8 eye and nasal irritation, smoke concentration vs. duration as factors, 235 health effects and public attitudes as factors in smoking restric- tions, 265 health hazards, increasing evidence as factor in regulation, 282, 286 health risks, 6-7, 107-108 infants and children, bronchitis and pneumonia risk, 38, 42-44 infants and children, respiratory system effects, 38-59 inflammatory cell numbers and functions in smokers, inferences, 944-245 irritant effects in nonsmokers in restaurants and offices, 232 irritation from gas phase vs. whole sidestream smoke, 236-238 lung cancer dose-response relation- ship, problems in exposure deter- mination, 92-93 lung cancer in spouses of smokers, prospective and case-control studies (table), 71 lung cancer in wives of smokers, Japanese prospective study, 73- 76 343 INDEX INVOLUNTARY SMOKING—Contd. lung cancer relationship, relative risk, 72 lung cancer risk, American Cancer Society Cohort Study, 76-77 lung cancer risk assessment, impor- tance of definition of exposure, 92 lung cancer risk, bias in case—con- trol studies (table), 98 lung cancer risk, epidemiological evidence, 97-98 lung cancer risk, evidence from case-control studies, 97 lung cancer risk factor in children, 90-91 lung cancer risk factor in non- smokers, 13 lung cancer risk in nonsmokers, Hong Kong case-control studies, 80-81 lung cancer risk in spouses of smokers, Louisiana case-control study, 79-80 lung cancer risk in spouses of smokers, Scottish study, 77-78 lung cancer risk in wives of smok- ers, Greek case-control study, 78-79 lung cancer risk relationship, case— control studies (table), 68-70 lung cancer risk relationship, Los Angeles County study, 83 lung cancer risk relationship, pre- liminary findings of U.S. study, 82 lung cancer risk relationship, pro- spective studies (table), 67 lung cancer risk relationship, sum- mary and conclusions, 96-102 lung cancer risk relationship, the Four Hospitals case-control study, 84-86 lung cancer risk relationship, the German case-control study, 90 lung cancer risk relationship, the Japanese case-control study, 88- 89 lung cancer risk relationship, the Swedish case-control study, 89- 90 lung cancer risk relationship, the United Kingdom case-control study, 86-88 344 INVOLUNTARY SMOKING—Contd. lung cancer risk, study power of case-control studies (table), 99- 100 lung disease risk, extrapolation from risk in smokers, 30-31 lung function effects in adult non- smokers, 60, 62 lung function effects in adults (ta- ble), 61 lung function effects in healthy adults (table), 64 mathematical models of lung can- cer risk, 93-96 middie ear effusions and diseases in children, risk relationship, 58-59 misclassification of smoking status and exposure as factors in deter- mining risk, 66-67, 72-73 nicotine and cotinine levels as ex- posure markers under real-life conditions, 207 nicotine and cotinine to quantify ETS exposure, 208, 215 organization of the 1986 Report, 5 personal monitoring to measure ex- posure, 33-34 personal monitors to measure ETS concentrations, 164-167 public and workplace smoking re- strictions, conclusions of 1986 re- port, 324 public awareness of health hazards as factor in changing attitudes, 320 quantitative and qualitative differ- ences in exposure from active smoking, 23-24 questionnaires for estimating expo- sure, uses and limitations, 34-35 research recommendations, 321-323 respirable suspended particulate levels as marker of smoke expo- sure, 8 respiratory system effects in chil- dren, case-control studies, 43-44 respiratory system effects in chil- dren, cross-sectional studies, 43 respiratory system effects in in- fants and children, longitudinal studies, 38, 42-43 State legislation in 1970s aimed at protecting nonsmokers, 267 INDEX INVOLUNTARY SMOKING—Contd. summary and conclusions of 1986 report, 12-13 thiocyanate levels not specific for exposure, 203 toxicity, mathematical model for estimating using “cigarette equivalents”, 198-200 urinary nicotine and expired car- bon monoxide in nonsmokers fol- lowing exposure, 207 workplace, lung cancer risk rela- tionship, 91-92 workplaces, current status of smok- ing regulations, 285-303 IRRITATION (See also RESPIRATORY SYMP- TOMS) acute effects of ETS exposure, 229- 239 allergic persons, ETS exposure ef- fect, 239 annoying and irritating effects of ETS, 231-239 children exposed to ETS, 239 ETS exposure effects, conclusions, 252 nonsmokers, experimental studies of ETS exposure effects, 233-239 LABORATORY SMOKING chemical analysis of sidestream smoke in special chambers, 127- 129, 132 mainstream and sidestream compo- sition data collection, 125 mainstream smoke particle size dis- tribution (table), 184-185 particle size of mainstream smoke aerosol, measurement, 182-183, 186 sidestream smoke particle size dis- tribution (table), 186 LEGISLATION (See also SMOKING REGULA- TIONS) average restrictiveness of State laws, 1960-1985 (figure), 276 comprehensiveness index of State laws, 327-328 current State smoking regulations, variations, 268-270 early restrictions as moral crusade and fire protection, 266-267 LEGISLATION—Contd. emphasis shift and increase in State legislation during the 1970s, 267 Federal, State, and local to restrict smoking, 266-278 impact on smoking behavior, as- sessment, 306-307 local, California’s nonsmokers’ rights movement as factor, 277 Minnesota, landmark Ciean Indoor Air Act of 1975, model for other States, 267 nonsmoking sections in restaurants mandated by State laws, 280 rate of new State legislation con- tinues into 1980s, 268 regional variation in State laws against smoking (table), 277 restrictions and bans on smoking, 16 review of impact on smoking be- havior, 320-321 smoking regulations, conclusions of 1986 report, 324 social norms and public attitudes as factors in passage, 321 State and local laws and Federal regulation in health care facili- ties, 284-285 State and local laws on public smoking, influence on private sector, 295 State and local smoking control statutes, implementation evalu- ation, 316-318 State, increase in comprehensive- ness of smoking regulations since 1970, 275 State laws regulating smoking in public places and workplaces (ta- ble), 271-274 State laws restricting smoking, 1970-1985 (table), 269 States with no regulations against smoking, 268 student smoking, legal incentive for regulation by schools, 282 tobacco-producing States have less restrictive laws on smoking, 275-276 workplace smoking, early contro- versy, 286 345 INDEX LEGISLATION—Contd. workplace smoking, private sector, State and local laws, 285 workplace smokin; regulation, vari- ations in State laws, 270, 275 LEUKEMIA children of women who smoked during pregnancy, risk relation- ship, 103-104 LEUKOCYTES polymorphonuclear, lung disease risk relationship in smokers, 243-244 LUNG CANCER (See also CANCER) animals exposed to cigarette smoke, 248-249 confounding variables in studies of ETS risk in nonsmokers, 36 ETS as risk factor in nonsmokers, 8-10 ETS exposure as risk in nonsmok- ers, Hong Kong case-control studies, 80-81 ETS risk relationship, need for more accurate estimates of expo- sure, 102 involuntary smokers, study power of case-control studies (table), 99-100 involuntary smoking as factor, American Cancer Society Cohort Study, 76-77 involuntary smoking as factor, Los Angeles County study, 83 involuntary smoking as factor, pre- liminary findings of U-S. study, 82 involuntary smoking as factor, rela- tive risk, 72 involuntary smoking as factor, the Four Hospitals case-control study, 84-86 involuntary smoking as factor, the German case-control study, 90 involuntary smoking as factor, the Japanese case-control study, 88- 89 involuntary smoking as factor, the Swedish case-control study, 89- 90 346 LUNG CANCER—Contd. involuntary smoking as factor, the United Kingdom case-control study, 86-88 involuntary smoking as risk factor, bias in case-control studies (ta- ble), 98 involuntary smoking as risk factor, case-control studies (table), 68- 70 involuntary smoking as risk factor, prospective studies (table), 67 involuntary smoking as risk factor, summary and conclusions, 96- 102, 107 involuntary smoking dose-response relationship, problems in expo- sure determination, 92-93 mathematical models of ETS expo- sure risk in nonsmokers, 93-96 methodological issues in assessing involuntary smoking risk, 66-67, 72-73 mortality in nonsmoking wives of smokers, 27 nonsmokers, case-control study evi- dence of ETS exposure as risk factor, 97 nonsmokers, epidemiological evi- dence of ETS exposure as risk factor, 97-98 nonsmokers, involuntary smoking as risk factor, 13, 66-101 nonsmokers, projection of ETS risk from relationship with smoking in smokers, 26-27 nonsmoking spouses of smokers, Louisiana case-control study, 79- 80 nonsmoking spouses of smokers, po- tential bias in Japanese study, 74-75 nonsmoking spouses of smokers, Scottish study, 77-78 nonsmoking wives of smokers, Jap- anese prospective study, 73-76 nonuniform carcinogenic particle deposition as possible risk factor, 192 parental smoking as risk factor, 90-91 sample size of concern in studies of nonsmokers, 22 smoking as major risk factor, 6 INDEX LUNG CANCER—Contd. spousal smoking as risk factor, pro- spective and case-control studies (table), 71 women married to smokers, Greek case-control study, 78-79 LUNG DISEASES (See also RESPIRATORY TRACT DISEASES) active smokers, extrapolation of risk in involuntary smokers, 30 bronchiolitis, early pathologic le- sions in smokers, 241 LUNG FUNCTION adult asthmatic nonsmokers ex- posed to cigarette smoke, 63, 65 adults exposed to involuntary smoking (table), 61 asymptomatic adults, long-term workplace exposure as risk fac- tor, 60 children and adolescents who start to smoke, 28 children and adults, conclusions about ETS exposure risk, 107 children, information needed on re- lationship with ETS exposure, 32 children, involuntary smoking risk relationship (table), 50-52 children, maternal smoking rela- tionship, 49, 53-54 healthy nonsmokers exposed to cig- arette smoke (table), 64 nonsmokers, ETS as factor in de- cline, 10 nonsmokers, extrapolation of ETS risk from risks in smokers, 27 LUNGS (See also RESPIRATORY SYSTEM) carbon monoxide deposition kinetics as factor in variations in concen- tration, 201-202 children of parents who smoke, possible long-term effects, 44 cigarette smoking effect, implica- tions for chronic ETS exposure, 239 cigarette smoking effects, summary, 246-247 inflammatory cell function, experi- mental models of cigarette smoke inhalation, 245-246 LUNGS—Contd. inflammatory cells, cigarette smok- ing effect, 241-246 inflammatory lesions in smokers vs. nonsmokers, 245 parenchyma alterations in smokers, 246 parenchyma destruction by poly- morphonuclear elastase in smok- ers, 243 regional deposition of mainstream smoke particles in smokers, 189, 191 respirable particle deposition, non- uniformity, 191-192 sidestream smoke particle deposi- tion, mass median diameter as factor, 187 MAINSTREAM SMOKE (See also CIGARETTE SMOKE; SIDESTREAM SMOKE; SMOKE STREAMS; TOBACCO SMOKE) condensates, in vitro assays of mu- tagenic activity, 250-251 definition, 7 electrical charge as factor in parti- cle deposition, 187 particle size distribution studies, 140 particle size distribution (table), 184-185 regional deposition in respiratory tract of smokers, 189, 191 respiratory system deposition vs. sidestream smoke (table), 190 MATERNAL SMOKING (See also PARENTAL SMOKING) asthmatic children, risk relation- ship, 55-58 brain tumors in children, risk rela- tionship, 104 cancer other than lung cancer in children, risk relationship, 103- 104 health risks for fetus and neonate, 6 leukemia in children of women who smoked during pregnancy, 103 jung function in children, risk rela- tionship, 49, 53-54 lung function in children, risk rela- tionship (table), 50-52 347 INDEX MATERNAL SMOKING—Contd. respiratory illness in children, case-control studies of risk, 43- 44 respiratory illness in children, cross-sectional studies of risk, 43 respiratory illness in infants and children, 38, 42-43 MATHEMATICAL MODELS airways deposition of sidestream smoke suggested, 217 humidity effect on particle size and deposition, 187-188 lung cancer risk of ETS exposure, "93-96 particle deposition patterns, effect of cigarette tar content, 191 regional deposition of polydisperse aerosols, 189 respirable suspended particulate constituent of ETS for exposure prediction, 165 respiratory tract deposition of side- stream smoke particles, 186-187 tracheobronchial smoke particle de- position prediction, age as factor, 192 MINNESOTA landmark Clean Indoor Air Act, model for other States, 267 public approval of 1975 Clean In- door Air Act, 318-319 MORTALITY cancers other than lung cancer, standard ratios for wives of smokers, 102 lung cancer, establishing risk in nonsmokers, 95-97 lung cancer in ETS exposed non- smokers, American Cancer Soci- ety Cohort Study, 76-77 lung cancer in nonsmoking wives of smokers, 27 lung cancer in spouses of smokers, Scottish study, 77-78 lung cancer in wives of smokers, Japanese prospective study, 73- 76 maternal smoking as risk factor for infant mortality, 6 348 MOTIVATION cessation of smoking, public atti- tudes and restrictions as rein- forcement, 305 worker safety not health as factor in early smoking regulations, 287 workplace smoking policies, effect on smoking cessation attempts, 313-314 workplace smoking regulation, 295- 296 NICOTINE (See also TOBACCO SMOKE CON- STITUENTS) absorption in nonsmokers to assess lung cancer risk, 9 absorption in populations suggests ETS exposure is common, 15 acute toxicity in animals as factor in smoke carcinogenicity testing, 247 atmospheric levels as marker of ETS exposure, 33 biological fluid levels, promising tracer of ETS exposure, 165-166 blood levels, metabolism, and excre- tion rate to determikne intake, 203-204 body fluid levels as marker of smoke exposure in nonsmokers, 8 body fluid levels increase with re- ported ETS exposure, 15, 217 body fluid levels specificity for to- bacco or tobacco smoke expo- sure, 204 ETS as source in general environ- ment, 14, 169 ETS exposure determination, speci- ficity, 147 ETS exposure quantification, 208, 215 ETS tracer, need for proper valida- tion, 168 measurement under realistic condi- tions (table), 155-156 personal air monitoring for intake determination, 216 plasma and urine levels from in- travenous infusion vs. ETS expo- sure in nonsmokers, 215 INDEX NICOTINE—Contd. plasma, urine, saliva levels in non- smokers vs. active smokers, 209- 210, 216 suspended particulate levels as measurement of ETS exposure, 193 tobacco smoke exposure determina- tion, absorption, distribution, me- tabolism, 203-205 vapor phase of sidestream vs. mainstream smoke, 127 NITROGEN OXIDES carcinogenic potential of oxides of nitrogen in sidestream smoke, 129 irritant in ETS, 229 measurement under realistic condi- tions (table), 157 nitrogen dioxide in sidestream smoke, carcinogenic potential, 129 NITROSAMINE CONTENT N-nitrosamines in sidestream vs. mainstream smoke, 129 NITROSAMINES ETS as only source of some N-ni- trosamine compounds in general environment, 169 ETS exposure determination, speci- ficity, 147 measurement under realistic condi- tions (table), 158 sidestream smoke levels higher than in mainstream smoke, 14 NONSMOKERS absorption of smoke constituents under experimental and natural exposure, 206-207 blood cotinine levels, nicotine injec- tion vs. smoke exposure, 215-216 California nonsmokers’ rights move- ment as factor in local smoking regulation, 277 cardiovascular disease, prospective and case-control studies of ETS risk, 105-106 chronic ETS exposure, inferred risk for respiratory epithelium, 240- 241 cotinine elimination half-life vs. smokers, 205-206 NONSMOKERS—Contd. emphysema risk vs. smokers, genet- ic predisposition as factor, 246 ETS as lung cancer risk factor, problems in exposure determina- tion, 92-93 ETS-exposed, plasma, urine, saliva cotinine vs. active smokers (ta- ble), 211-214 ETS-exposed, plasma, urine, saliva nicotine vs. active smokers (ta- ble), 209-210 ETS exposure, experimental studies of irritant effects, 233-239 ETS exposure, relationships with active smoking provide insight into risks, 26-28 ETS exposure toxicity, mathemati- cal model using “cigarette equiv- alents”, 198-200 ETS exposure, wide variations, 14 health risks of ETS exposure, con- clusions, 107-108 health risks of involuntary smok- ing, summary and conclusions, 12-13 irritant effects of involuntary smoking in restaurants and of- fices, 232 irritation from sidestream smoke vs. gas phase sidestream smoke, 236-238 irritation from smoke exposure, concentration vs. duration as factors, 235 lung cancer, establishing risk of ETS exposure, 95 lung cancer, ETS exposure as fac- tor, Four Hospitals case-control study, 84-86 lung cancer, ETS exposure as fac- tor, German case-control study, 90 lung cancer, ETS exposure as fac- tor, Hong Kong case-control study, 80-81 lung cancer, ETS exposure as fac- tor, Japanese case-control study, 88-89 lung cancer, ETS exposure as fac- tor, Los Angeles County study, 83 349 INDEX NONSMOKERS—Contd. lung cancer, ETS exposure as fac- tor, preliminary findings of US. study, 82 lung cancer, ETS exposure as fac- tor, Swedish case-control study, 89-90 lung cancer, ETS exposure as fac- tor, United Kingdom case—con- trol study, 86-88 lung cancer in spouses of smokers, prospective and case-control studies (table), 71 lung cancer, involuntary smoking as risk factor, 13 lung cancer risk from ETS expo- sure, 8-10 lung cancer risk from ETS as pro- jection of relationship of smok- ing in smokers, 26-27 lung cancer risk in spouses of smokers, Japanese prospective study, 73-76 lung cancer risk in spouses of smokers, Louisiana case-control study, 79-80 lung cancer risk in spouses of smokers, Scottish study, 77-78 lung cancer risk of ETS exposure, American Cancer Society Cohort Study, 76-77 lung cancer risk of involuntary smoking, case-control studies (ta- ble), 68-70 lung cancer risk of involuntary smoking, more accurate data needed, 102 Jung function in healthy adults ex- posed to cigarette smoke (table), 64 mathematical models of lung can- cer risk with ETS exposure, 93- 96 misclassification of status and ETS exposure as factors in determin- ing risk, 66-67, 72-73 nicotine and cotinine to quantify ETS exposure, 208, 215 odor perception and irritation, in- fluence of room temperature and humidity, 234 plasma and urine nicotine levels, intravenous vs. ETS exposure ef- fect, 215 350 NONSMOKERS—Contd. plasma, saliva, and urine nicotine and cotinine levels vs. active smokers, 216 preferential hiring, most restrictive smoking policy, 301-302 private, local, governmental actions for protection from smoke expo- sure, 265 respirable suspended particulates in ETS-exposed vs. nonexposed, 169 review of impact of smoking re- strictions on attitudes, 320 separation from smokers for risk reduction, effectiveness, 11-12 State antismoking legislation in 1970s aimed at protection, 267 temporal and spatial distribution of smokers in ETS exposure deter- mination, 145-146 urinary cotinine levels in ETS-ex- posed vs. nonexposed men, 207 urinary nicotine and expired car- bon monoxide, effects of smoke exposure, 207 workplace bans for maximum pro- tection, momentum growing among large employers, 301 workplace demands for clean air as motivation for smoking regula- tions, 296 workplace smoking as eye irritant, 233 workplace smoking as lung cancer risk factor, 91-92 NOSE annoying and irritating effects of ETS exposure, 231, 235 ETS particle deposition, effect of nasal inhalation, 189 smoke concentration vs. exposure duration as factors in irritation, 235 PARENTAL SMOKING (See also MATERNAL SMOKING) cancers other than lung cancer in children, risk relationship, 102- 105 cough, phlegm, and wheezing in children, 44, 47-49 lung cancer risk relationship, 90-91 lung function in children, relation- ship (table), 50-52 INDEX PARENTAL SMOKING—Contd. lung function in children, risk rela- tionship, 53-54 middle ear effusions and diseases in children, risk relationship, 58-59 respiratory illness in infants and children, 38, 42-44 respiratory symptoms in children, 13 respiratory symptoms in children, relationship (table), 45~46 respiratory system effects in chil- dren, 38-59 saliva cotinine concentrations in children, effect, 207-208 Passive Smoking See INVOLUN- TARY SMOKING PHYSICAL ACTIVITY ETS deposition increase with in- creasing activity, 187 PREGNANCY fetal exposure to tobacco smoke constituents, possible effects, 31- 32 leukemia risk in children of smok- ers, 103 PUBLIC PLACES (See also HOSPITALS; WORK- PLACE) current status of smoking regula- tions mix of public and private actions, 265-266 employee attitudes before smoking policy implementation, 311 health care facilities, public sup- port of smoking restrictions, 284 health care facilities, smoking regu- lations, 283-285 hotels and motels, smoking regula- tions, 281-282 impact of public and workplace policies restricting smoking, 303- 321 interstate transportation, smoking regulated at Federal level, 278 legislation restricting smoking, evaluation of impact, 316-318 local smoking regulations, 277-278 public transportation, smoking reg- ulations, 278-279 PUBLIC PLACES—Contd. research recommendations on ef- fects of smoking regulations, 321 restaurants, opposition, acceptance, and implementation of smoking restrictions, 280 restaurants, smoking regulations, 279-281 retail stores, smoking regulations, 279 schools, smoking regulations, 282- 283 smoking regulation, State laws (ta- ble), 271-274 smoking regulations, conclusions of 1986 report, 324 smoking regulations, factors in ac- ceptability, 266 smoking regulations in specific public places, 278-285 smoking regulations, public approv- al, national and regional polls, 318-319 smoking restrictions, variations in current State legislation, 268- 270 State laws regulating smoking, comprehensiveness index, 327- 328 State legislation to restrict smok- ing, increase during the 1970s, 267 States restrict smoking in transpor- tation, hospitals, elevators, and others, 269 total suspended particulates (table), 194-195 PULMONARY ALVEOLAR MAC- ROPHAGES lung injury relationship in smok- ers, 241-243, 245 protease-antiprotease balance in lungs of smokers, influence, 242—243 respiratory bronchioles of smoke-ex- posed animals, 245-246 PYRIDINES sidestream vs. mainstream smoke levels, 129 RADIATION decay products of radon in tobacco smoke, 132, 134 ETS radioactivity, 134 351 INDEX REDUCTION OF SMOKING (See also CESSATION OF SMOK- ING) public attitudes and smoking poli- cies as indirect influences, 304~ 305 RESIDENCES total suspended particulates (table), 195-196 RESPIRABLE SUSPENDED PAR- TICULATES enclosed places, ETS role, 169 ETS-exposed and nonexposed sam- ples, percentage distribution, 167 hospital before and after adopting restrictive smoking policy, 311 irritants in ETS, 229 marker for ETS exposure, 33-34 personal monitors to measure ETS exposure, 166-168 residental levels as function of number of smokers (table), 164 respiratory disease risk in children of smokers, 192 : tracheobronchial deposition in in- fants vs. adults, prediction, 192 RESPIRATORY FUNCTION TESTS children, involuntary smoking as risk factor, 53-54 nonsmokers exposed to involuntary smoking, 62-63 predicted levels, relationship with number of cigarettes smoked, 29 RESPIRATORY SYMPTOMS (See also COUGH; IRRITATION; NOSE) annoying and irritating effect of ETS exposure, 231-232, 238-239 children and adolescents who start to smoke, 27 children and adults, ETS exposure as factor, conclusions, 107 ‘children, parental smoking as fac- tor, 13 children, relationship with inyolun- tary smoke exposure (table), 45- 46 cough, phlegm, and wheezing in - adults, ETS exposure as risk not established, 60 352 RESPIRATORY SYMPTOMS—Contd. cough, phlegm, wheezing in chil- dren, parental smoking as factor, 44, 47-49 involuntary smokers, 31 RESPIRATORY SYSTEM (See also LUNGS) animals, carcinogenicity of cigarette smoke, 247-248 breathing pattern and particle size distribution effect on ETS dose, 25 breathing patterns as factor in sidestream smoke deposition, 187 bronchoconstriction in children, pa- rental smoking as risk factor, 55-58 bronchoconstriction in normal adults exposed to involuntary smoking, 63 cigarette smoking effects, implica- tions for involuntary smoking risks, 239-241 deposition and absorption of tobac- co smoke constituents, 181-216 deposition of mainstream and side- stream smoke, 25 . enzyme activity in smoke-exposed animals, 245 : epithelial cells, dose-response effect of cigarette smoking, 239 ETS deposition, 193-216 ETS dose, product of mass in in- haled air and deposition frac- tion, 193 hyperplasia and metaplasia in tra- chea and bronchi of smoke-ex- posed animals, 248 involuntary smoking effects, 37-65 mass deposition of ETS, estimation, 193 nasal vs. mouth inhalation of ETS, effect on particle deposition, 189 nose, throat, and airway irritation from smoke exposure, 11 particle size of cigarette smoke as _ factor in deposition, 182 puffing and inhalation patterns as factor in particle deposition, 183 regional deposition of smoke parti- cles, 189, 191 sidestream and mainstream smoke deposition (table), 190 INDEX RESPIRATORY SYSTEM—Contd. sidestream smoke particle deposi- tion, 186-189 smoke particle size as factor in re- gional deposition, 189, 191-192 RESPIRATORY TRACT CANCER animals exposed to cigarette smoke, 248 RESPIRATORY TRACT DISEASES acute illness in children, parental smoking as risk factor, 38, 42-44 asthma in children, maternal smoking as risk factor, 55-58 children, case-control studies of pa- ternal smoking as risk factor, 43-44 children, nonuniform deposition of smoke particles as risk factor, 192 children, parental smoking as fac- tor, 13 - children, parental smoking as risk factor, 38-59 early childhood, involuntary smok- ing relationship (table), 39-41 involuntary smoking as risk factor, 10 nonsmoking adults and children, involuntary smoking as factor, 37-66 pneumonia in children of smokers, conclusions about risk, 107 population characteristics as factor in ETS risk, 28 smoking as major risk factor, 6 RESPIRATORY TRACT INFEC- TIONS children of smokers, conclusions about risk, 107 infants, ETS exposure as risk fac- tor, 31 SALIVA cotinine level as marker for ETS exposure in nonsmokers, 36 cotinine levels in ETS-exposed non- smokers vs. active smokers (ta- ble), 211-214 nicotine and cotinine levels to quantify ETS exposure, 208, 215 nicotine levels as sidestream smoke exposure indicator, 204-205 SALIVA—Contd. nicotine levels in ETS-exposed non- smokers vs. active smokers (ta- ble), 209-210 nicotine levels in nonsmokers vs. smokers, 216 SIDESTREAM SMOKE (See also CIGARETTE SMOKE, MAINSTREAM SMOKE; SMOKE STREAMS; TOBACCO SMOKE) bioassays needed to determine gen- otoxicity, 252 carbon monoxide and carbon diox- ide levels vs. mainstream smoke, 129 carcinogen levels vs. mainstream smoke, 24 carcinogenic potential, effect of lev- els of oxides of nitrogen, 129 carcinogenicity vs. mainstream smoke in animal models, 252 chemical analysis, 127-129, 132 chemical composition as factor in estimating exposure using “ciga- rette equivalents”, 199 component levels, combustion tem- perature effect vs. mainstream smoke, 128-129 constituent formation vs. main- stream smoke, 7-8 definition, 7 experimental and mathematical models show deposition in air- ways, 217 formaldehyde and acrolein concen- trations above occupational lim- its, 230 formation and physiochemical na- ture, 127 inhalation effects in laboratory ani- mals not reported, toxicity fac- tor, 249 irritation in nonsmokers vs. gas phase sidestream smoke vs. acro- lein, 236-237 irritation of nonsmokers in labora- tory, ventilation as factor, 234- 235 laboratory collection devices, 125~ 126 major source of ETS, 125 353 INDEX SIDESTREAM SMOKE—Contd. mass median diameter, effect on deposition in respiratory tract, 187 mathematical models of particle de- position in respiratory tract, 186-187 nicotine in vapor phase vs. main- stream smoke, 127 particle distribution in respiratory tract, 186-189 particle size distribution studies (ta- ble), 138 particle size distribution (table), 186 particles, number and size distribu- tion, 137, 139 particulate matter vs. mainstream smoke, 129, 132 particulate phase as major determi- nant of irritation in nonsmokers, 237-238 physiochemical nature and spec- trum of carcinogens, summary, 251-252 regional deposition in respiratory tract, particle size as factor, 189, 191-192 respiratory system deposition vs. mainstream smoke (table), 190 saliva nicotine levels as indicator of exposure, 204-205 toxic and carcinogenic agents, 21 toxic and carcinogenic compounds, 14 toxic and carcinogenic compounds vs. mainstream smoke, conclu- sions, 169 tumor induction by condensate on mouse skin vs. mainstream smoke condensate, 250 vapor and particulate phase con- stituents, sidestream to main- stream ratio (table), 130-131 SMOKE INHALATION, ANIMAL carcinogenicity testing, 247-250 laryngeal leukoplakias in hamsters, 248-249 lung and respiratory cancers in mice and rats, 248 lung inflammatory cell function, experimental models, 245-246 354 SMOKE STREAMS (See also CIGARETTE SMOKE; MAINSTREAM SMOKE; SIDE- STREAM SMOKE; TOBACCO SMOKE) combustion temperature effect on components of sidestream vs. mainstream smoke, 128-129 mainstream and sidestream smoke, comparison, 23-25 mainstream smoke vs. ETS, chemi- cal composition, 135, 137 mainstream vs. sidestream smoke from unfiltered cigarette, com- parison (table), 128 particulate matter in mainstream and sidestream smoke, 129, 132 sidestream and mainstream smoke inhalation by smokers and invol- untary smokers, 126-127 toxic and carcinogenic agents in in- door mainstream vs. ETS (table), 136 vapor and particulate phase con- stituents, sidestream to main- stream ratio (table), 130-131 SMOKING immune system effects, 244 public knowledge and attitudes, policy impact assessment by sur- veys, 307 public places and workplaces, State regulations (table), 271-274 regulatory approaches of State and local governments, 278 SMOKING CHARACTERISTICS compensatory smoking by workers following smoking policy imple- mentation, 312-313 machine smoking simulation, incon- sistency with current patterns, 126-127 puffing and inhalation effect on particle deposition, vs. machine smoking, 183 SMOKING CONTROL PROGRAMS evaluation, methodological consider- ations, study design as factor, 306-308 guides on how to adopt and imple- ment regulatory policies, 302 INDEX SMOKING CONTROL PROGRAMS—Contd. ‘individual solution” approach to control workplace smoking, 298 separating smokers and nonsmok- ers, improving workplace ventila- tion, 299 workplace cessation of smoking programs as part of control poli- cies, 297 workplace restrictions on where smoking is allowed, variations, 299-300 SMOKING HABIT consumption decline, effect of pub- lic attitudes and social norms, 321 population group differences in ETS exposure determination, 145-146 research recommendations on effect of smoking restrictions, 322 smoking restrictions with most im- pact on behavior, research need- ed, 323 SMOKING MACHINES (See also LABORATORY SMOK- ING) human smoking simulation incon- sistent with current patterns, 126-127 standard conditions for machine smoking cigarettes, 125 SMOKING REGULATIONS (See also LEGISLATION) assessment of effect on air quality, 307 average restrictiveness of State laws, 1960-1985 (figure), 276 case-control studies of impact on human behavior, evaluation, 306 current State legislation, variations, 268-270 designated smoking or no-smoking areas to control workplace smok- ing, 299-300 employer-mandated policies in the private sector, opposition, 296- 297 enforcement costs, experience con- tradicts tobacco industry esti- mates, 316 SMOKING REGULATIONS—Contd. geographic variability of State laws on smoking in public places (fig- ure), 270 health care facilities, 283-285 health care facilities, public sup- port, 284 health care facilities, variations in policies, 284-285 hospitals, awareness and compli- ance, 309-310 hospitals, effect on air quality, 311 hospitals, employee approval of pol- icies, 312 hospitals, positively worded signs and enforcement factors in com- pliance, 310 hospitals, review of current evi- dence of impact, 308-309 hotels and motels, private initiative in response to perceived demand, 281-282 hotels and motels, public support, 281-282 impact on air quality, behavior, at- titudes, 303-321 implementation, 309-310 implementation, assessment of im- pact, 307-308 implementation of workplace poli- cies, 302-303 implementation, smokers’ support as factor, 303-304 legislation to restrict smoking in public places, 266-276 local legislative restrictions, 277- 278 local restrictions, California’s non- smokers’ rights movement as factor, 277 nonsmoker’s exposure to second- hand smoke, assessment of im- pact, 306 policy components that impact on smoking behavior, research need- ed, 323 preferential hiring of nonsmokers as most restrictive policy, 301- 302 public and private organizations, employees’ attitudes, 311-312 public and workplace, conclusions of 1986 report, 324 355 INDEX SMOKING REGULATIONS—Contd. public and workplace control poli- cies, indirect effects, 304-305 public and workplace restrictions, review of impact, 303-321 public approval, national and re- gional polls, 318-319 public awareness, compliance, and enforcement of violations in im- plementation, 303 public places and workplaces, Fed- eral, State, and local action, 15- 16 public places and workplaces, State laws (table), 271-274 public places, current status mix of public and private actions, 265- 266 public places, factors in acceptabili- ty, 266 public places, role of public atti- tudes and social norms, 321 public support, 16 public transportation, 278-279 regional variation in State laws against smoking (table), 277 research must consider policy char- acteristics, institution, and popu- lation, 321-323 research recommendations, 321-323 restaurants, 279-281 restaurants, opposition, acceptance, and implementation, 280 retail stores, 279 review of impact on attitudes and social norms, 319-320 schools, difficulties in enforcement, 283 schools, double standard of teacher smoking vs. student restrictions, 283 schools, traditionally not to reduce sidestream smoke exposure, 282 social phenomenon, impact infor- mation lacking, need for re- search, 323 specific public places, 278-285 State and local governments, re- strictions, 12 State and local statutes, implemen- tation evaluation, 316-318 State laws, comprehensiveness in- dex, 327-328 356 SMOKING REGULATIONS—Contd. State laws restricting smoking, 1970-1985 (table), 269 State legislation, emphasis shift and increase during the 1970s, 267 State legislation in 1970s aimed at protecting nonsmokers, 267 State legislation, increase in comprehensiveness, 275 States with no smoking legislation, 268 tobacco-producing States, fewer enacted and less restrictive, 275- 276 worker safety as motivation for early policies, 287 workplace ban, complexity of assur- ing compliance, 301-302 workplace bans, usually preceded by progressively stricter regula- tions, 300-301 workplace, barriers to adopting pol- icies, 296-297 workplace, categories of policies, 298 workplace compliance with local or- dinances, type of business as fac- tor, 317 workplace, current evidence of im- pact, 308-309 workplace, current status, 285-303 workplace, early controversy in the private sector, 286 workplace, economic considerations apparently not a factor, 296 workplace, effect on smoking cessa- tion motivation and success, 313-315 workplace, employee attitudes be- fore policy implementation, 311 workplace, impact on absenteeism, health care costs, productivity, turnover, 315-316 workplace, impact on health care and maintenance costs, 305 workplace, influence of nonsmok- ers' demand for clean air, 286 workplace, nature, scope, and prev- alence in the 1980s, 294-295 workplace, policy implementation effect on smokers’ behavior, 312- 313 INDEX SMOKING REGULATIONS—Contd. workplace, prevalence, 286-287, 294-295 workplace, public vs. private sector, 270 workplace, worker health, State legislation, nonsmokers’ demands as factors, 295-296 workplace, workforce size, industry type, geographic location as fac- tors, 295 workplaces, survey data 1977-1986 (table), 288—293 SMOKING STATUS (See also SMOKING HABIT) misclassification as factor in deter- mining ETS risk, 98, 101 misclassification as factor in deter- mining health risks of involun- tary smoking, 66-67, 72-73 SMOKING SURVEYS workplaces, 287, 294-295 STATISTICS significance testing of ETS risks, 36-37 TARS, CIGARETTE carcinogenicity testing in animals, 247-248 chemical assay for human exposure to components, research goal, 217 tumor induction on mouse skin, sidestream vs. mainstream con- densates, 250 TARS, TOBACCO particulates measured under realis- tic conditions (table), 159-162 sidestream smoke particle size dis- tribution studies (table), 138 THIOCYANATES sources, metabolism, elimination, half-life, 202-203 TOBACCO SMOKE (See also CIGARETTE SMOKE; MAINSTREAM SMOKE; SIDE- STREAM SMOKE; SMOKE STREAMS) absorption during active smoking vs. involuntary smoking, 215-216 TOBACCO SMOKE—Contd. biological markers of smoke absorp- tion in smokers and nonsmokers, 181 machine vs. human smoking, non- comparability of chemical and physiochemical data, 135 mainstream vs. environmental, characteristics, 6 nicotine in vapor phase, sidestream vs. mainstream, 127 odor perception and irritation, in- fluence of room temperature and humidity, 234 particle size distribution of main- stream smoke (table), 184-185 particle size distribution of side- stream smoke (table), 186 quantitatively determined com- pounds in sidestream and main- stream smoke, 128 radioactivity, 132, 134 residuals, measured under realistic conditions (table), 163 vapor phase, retention by smokers vs. involuntary smokers, 126-127 workplace air pollution, contribu- tion (table), 233 TOBACCO SMOKE CONSTITU- ENTS (See also COTININE; NICOTINE) absorption in nonsmokers under experimental and natural expo- sures, 206-207 chemical assay for human exposure to tar components, research goal, 217 deposition and absorption, 181-216 deposition fraction of individual components needed to determine disease risk, 200 ETS and mainstream differences as factor in exposure of nonsmokers vs. smokers, 201 ETS exposure quantification, 208, 215 irritants also produced by other sources, 229-230 irritants in ETS, 229 nicotine, absorption, distribution, metabolism, and body fluid lev- els, 203-205 357 INDEX TOBACCO SMOKE CONSTITU- ENTS—Contd. particle deposition in lung areas, nonuniformity, cancer risk rela- tionship, 192 trapping devices to analyze individ- ual components, 126 TOBACCO SMOKE PARTICU- LATES carcinogenicity testing in animals, 247-248 indoor concentrations by cigarette smoking under laboratory condi- tions (table), 197 irritation in nonsmokers vs. gas phase of sidestream smoke, 237- 238 potential toxicity estimation using “cigarette equivalents”, deficien- cies, 199 total suspended particulates in in- door working and living environ- ments (table), 194-196 URINE cotinine level as marker for ETS exposure in nonsmokers, 36 cotinine levels in ETS-exposed non- smokers vs. active smokers (ta- ble), 211-214 cotinine levels in ETS-exposed vs. nonexposed men, 207 mutagenic activity not good mea- sure of tar absorption, 206 nicotine and cotinine levels to quantify ETS exposure, 208, 215 nicotine excretion, individual me- tabolism as factor in smokers and nonsmokers, 203-205 nicotine levels in ETS-exposed non- smokers vs. active smokers (ta- ble), 209-210 nicotine levels in nonsmokers vs. smokers, 216 VENTILATION ETS components elimination, major factor, 146-147, 164-165 ETS, determinant of exposure, 11 ETS, effect on levels, 229 ETS, factor in estimating human exposure, 139, 141-142 involuntary smoking exposure, fac- tor, 67 restaurants, inadequate control of ETS levels, 279 358 VENTILATION—Contd. sidestream smoke in laboratory, ef- fect on perceived irritation in nonsmokers, 234-235 WOMEN cancers other than lung cancer in nonsmokers married to smokers, 102 lung cancer in wives of smokers, Greek case-control study, 78-79 lung cancer, involuntary smoking as factor, German case-control study, 90 lung cancer risk in wives of smok- ers, Japanese prospective study, 73-76 lung cancer risk with ETS expo- sure, Hong Kong case-control studies, 80-81 WORKPLACE (See also PUBLIC PLACES) barriers to adopting smoking poli- cies, 296-297 carbon monoxide, nitrogen, and particulate matter levels due to tobacco smoke, 232 categories of smoking policies, 298 compliance with local smoking or- dinances, type of business as fac- tor, 317 health care and maintenance cost reduction as benefit of smoking policy, 305 hospitals, employee approval of smoking policies, 312 involuntary smoking, irritant ef- fects, 232 irritants, tobacco smoke and other sources, 229-230 preferential hiring of nonsmokers as most restrictive smoking poli- cy, 301-302 research recommendations on effect of smoking regulations, 321 safety as motivation for early regu- lations against smoking, 287 smoking policies, survey data 1977- 1986 (table), 288—293 smoking restrictions, conclusions of 1986 report, 324 State laws regulating smoking, comprehensiveness index, 327- 328 INDEX WORKPLACE—Contd. surveys of smoking policies, 287, 294-295 tobacco smoke contribution to air pollution (table), 233 total suspended particulates (table), 194-195 WORKPLACE SMOKING (See also ENVIRONMENTAL TO- BACCO SMOKE; INVOLUN- TARY SMOKING) bans, usually preceded by progres- sively stricter regulations, 300- 301 business type as factor in compli- ance with local smoking ordi- nances, 317 cessation programs as part of pri- vate sector smoking control, 297 control by restricting where smok- ing is allowed, variations, 299- 300 ETS exposure determination, factor, 142 eye irritation reported in nonsmok- ers, 233 government offices, smoking regula- tion increasing, 285 guides on how to adopt and imple- ment smoking policies, 302 hospitals, awareness and compli- ance of employees, 309-310 hospitals, review of current evi- . dence on impact of smoking reg- ulations, 308-309 impact of public and workplace re- strictions, 303-321 WORKPLACE SMOKING—Contd. “individual solution” approach to regulation, 298 legislated restriction, early contro- versy, 286 lung cancer risk factor in non- smokers, 91-92 lung function effects of exposure in nonsmokers, 60 motivation for regulation, 295-296 nature, scope, and prevalence of regulation in the 1980s, 294-295 policy implementation effect on smokers, 312-313 private sector regulation, legislation and public support as factors, 295 private sector, State and local leg- islation, 285 regulation, impact on absenteeism, health care costs, productivity, turnover, 315-316 regulations, current status, 285-303 regulations supported by smokers and nonsmokers, 285 regulations, workforce size, geo- graphic location, type of indus- try as factors, 295 restrictions, 16 restrictions, voluntary vs. govern- mental, 12 schools, restrictions to reduce facul- ty/staff exposure to ETS, 282 State regulation, public vs. private sector, 270 State regulations (table), 271-274 urinary cotinine levels as marker of exposure in nonsmokers, 207 359