KNUDSON, R.J., BURROWS, B., LEBOWITZ, M.D. The maximal expiratory flow- volume curve: Its use in the detection of ventilatory abnormalities in a population study. American Review of Respiratory Disease 114(3): 871-879, November 1976. KNUDSON, R.J., CLARK, D.F., KENNEDY, T.C., KNUDSON, D.W. Effect of aging alone on mechanical properties of the normal adult human lung. Journal of- Applied Physiology: Respiratory, Environmental and Exercise Physiology 43(6): 1054-1062, December 1977. KNUDSON, R.J., LEBOWITZ, M.D. Comparison of flow-volume and closing volume variables in a random population. American Review of Respiratory Disease 116(6): 1039-1045, December 1977. KNUDSON, R.J., KALTENBORN, W.T. Evaluation of lung elastic recoil by exponen- tial curve analysis. Respiratory Physiology 46: 29-42, 1981. KNUDSON, R.J., LEBOWITZ, M.D., HOLBERG, C.J., BURROWS, B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. American Review of Respiratory Disease 127(6): 725-734, June 1983. KRUMHOLZ, R.A., HEDRICK, E.C. Pulmonary function differences in normal smoking and nonsmoking, middle-aged, white-collar workers. American Review of Respiratory Disease 107(2): 225-230, February 1973. KRZYZANOWSKI, M. Changes of ventilatory capacity in an adult population during - a five-year period. Bulletin Europeen de Physiopathologie Respiratoire 16(2): 155- 170, 1980. KUEPPERS, F., BLACK, L.F. Alphai-antitrypsin and its deficiency. American Review of Respiratory Disease 110(2): 176-194, August 1974. KUEPPERS, F., MILLER, R.D., GORDON, H., HEPPER, N.G., OFFORD, K. Familial prevalence of chronic obstructive pulmonary disease in a matched pair study. American Journal of Medicine 63: 336-342, September 1977. LAM, S., ABBOUD, R.T., CHAN-YEUNG, M., TAN, F. Use of maximal expiratory flow-volume curves with air and helium-oxygen in the detection of ventilatory abnormalities in population surveys. American Review of Respiratory Disease 123(2): 234-237, February 1981. LARSSON, C. Natural history and life expectancy in severe alpha-antitrypsin deficiency, PiZ. Acta Medica Scandinavica 204(5): 345-351, May 1978. LARSSON, C., ERIKSSON, S., DIRKSEN, H. Smoking and intermediate alpha-1- antitrypsin deficiency and lung function in middle-aged men. British Medical Journal 2(6092): 922-925, October 8, 1977. LEBOWITZ, M.D. Occupational exposures in relation to symptomatology and lung function in a community population. Environmental Research 14(1): 59-67, August - 1977a. LEBOWITZ, M.D. The relationship of socio-environmental factors to the prevalence of obstructive lung diseases and other chronic conditions. Journal of Chronic Diseases 30(9): 599-611, September 1977b. LEBOWITZ, M.D. Respiratory symptoms and disease related to alcohol consumption. American Review of Respiratory Disease 123(1): 16-18, January 1981. LEBOWITZ, M.D., BURROWS, B. Quantitative relationships between cigarette smoking and chronic productive cough. International Journal of Epidemiology 6(2): 107-113, June 1977. . LEBOWITZ, M.D., KNUDSON, R.J., BURROWS, B. Tucson Epidemiologic study of - obstructive lung diseases. I: Methodology and prevalence of disease. American - Journal of Epidemiology 102(2): 137-152, August 1975. LEBOWITZ, M.D., KNUDSON, R.J., BURROWS, B. Family aggregation of pulmonary function measurements. American Review of Respiratory Disease 129(1): 8-11, - 1984. LEBOWITZ, M.D, KNUDSON, R.J., BURROWS, B. Risk factors for airways obstruc- tive diseases: A multiple logistics approach. Chest 85(6): 11s-12s, June 1984, Supplement. 176 LEEDER, 8.R., COLLEY, J.R.T., CORKHILL, R., HOLLAND, W.W. Change in respiratory symptom prevalence in adults who alter their smoking habits. American Journal of Epidemiology 105(6): 522-529, 1977. LEFCOE, N.M., ASHLEY, M.J., PEDERSON, L.L., KEAYS, J.J. The health risks of passive smoking. The growing case for control measures in enclosed environments. Chest 84(1): 90-95, 1983. LEFCOE, N.M., WONNACOTT, T.H. Chronic respiratory disease in four occupational groups. Archives of Environmental Health 293): 143-146, September 1974. LIANG, A., MACFIE, A.E., HARRIS, E.A., WHITLOCK, R.M.L. Transit-time analysis of the forced expiratory spirogram during clinical remission in juvenile asthma. Thorax 34(2): 194-199, April 1979. LIARD, R., PEDRIZET, S., COOREMAN, J », BIDOU, S. Smoking and chronic respiratory symptoms: Prevalence in male and female smokers. American Journal of Public Health 70(3): 271-273, March 1980. LINN, W.W., HACKNEY, J.D., PEDERSEN, E.E., BREISACHER, P., PATTERSON, J.V., MULRY, C.A., COYLE, J.-F. Respiratory function and symptoms in urban office workers in relation to oxidant air pollution exposure. American Review of Respiratory Disease 114(3): 477-483, September 1976. LOVE, R.G., MILLER, B.G., Longitudinal study of lung function in coal-miners. Thorax 37(3): 193-197, March 1982. MACFIE, A.E., HARRIS, E.A., WHITLOCK, R.M.L. Transit-time analysis of the forced spirogram in healthy children and adults. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 46(2): 263-267, February 1979. MACKLEM, P.T., MEAD, J. Resistance of central and peripheral airways measured by retrograde catheter. Journal of Applied Physiology 22(3): 395-401, March 1967. MACNEE, W., POWER, J., INNES, A., DOUGLAS, N.J., SUDLOW, M.F. The dependence of maximal flow in man on the airway gas physical properties. Clinical Science 65(3): 273-279, September 1983. MADISON, R., MITTMAN, C., AFIFI, A.A., ZELMAN, R. Risk factors for obstructive lung disease. American Review of Respiratory Disease 124: 149-153, August 1981. MANFREDA, J., NELSON, N., CHERN TACK, R.M. Prevalence of respiratory abnormalities in a rural and an urban community. American Review of Respira- tory Disease 117(2): 215-226, February 1978. MARAZZINI, L., PELOSI, V., VEZZOLI, F., PENNASI, R., LONGHINI, E. Prospec- tive study of airway obstruction in a population with small airway disease. Bulletin Europeen de Physiopathologie Respiratoire 13(2): 219-229, March-April 1977. MARAZZINI, L. VEZZOLI, F., LONGHINI, E. Respiratory function 8 years after a diagnosis of peripheral airways disease. Respiration 42(2): 88-97, 1981. MARCQ, M., MINETTE, A. Lung function changes in smokers with normal conventional spirometry. American Review of Respiratory Disease 114(4): 723-738, October 1976. McCARTHY, D.S., CRAIG, D.B., CHERNIACK, R.M. Effect of modification of the smoking habit on lung function. American Review of Respiratory Disease 114(1): 103-113, July 1976. McCARTHY, D.S., SPENCER, R., GREENE, R., MICLIC-EMILI, J. Measurement of “closing volume” as a simple and sensitive test for early detection of small airway disease. American Journal of Medicine 52: 747-753, June 1972. MEAD, J. Problems in interpreting common tests of pulmonary mechanical function. In: Macklem, P.T., Permutt, S. (Editors). The Lung in the Transition Between Health and Disease. New York, Marcel Dekker, Inc., 1979, pp. 43-51. MEDICAL RESEARCH COUNCIL COMMITTEE ON THE AETIOLOGY OF CHRON. IC BRONCHITIS. Standardized questionnaires on respiratory symptoms. British Medical Journal 2(5213): 1665, December 3, 1960. 177 MENDELSSOHN, A. Journal of the Russian National Health Society, September 1897. Lancet 2(3867): 952-953, 1897. MICHAELS, R.. SIGURDSON, M., THURLBECK, S., CHERNIACK, R. Elastic recoil of the lung in cigarette smokers: the effect of nebulized bronchodilator and cessation of smoking. American Review of Respiratory Disease 11%5): 707-716, May 1979. MILLER, A., THORNTON, J.C.. WARSHAW, R., ANDERSON, H., TEIRSTEIN, A.S., SELIKOFF, I.J. Single breath diffusing capacity in a representative sample of the population of Michigan, a large industrial state. Predicted values, lower limits of normal, and frequencies of abnormality by smoking history. American Review of Respiratory Disease 127(3): 270-277, March 1983. MILNE, J.S. Longitudinal respiratory studies in older people. Thorax 33: 547-554, 1978. MIMICA, M. Study of Regional Prevalence and Incidence of Chronic Bronchitis and Asthma in Adults. Final Report. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, January 1975. MINK, S.N., WOOD, L.D.H. How does HeQ. increase maximum expiratory flow in human lungs? Journal of Clinical Investigation 66(4): 720-729, October 1980. MITCHELL, R.S., STANFORD, R.E., JOHNSON, J.M., SILVERS, G.W., DART, G., GEORGE, M.S. The morphologic features of the bronchi, bronchioles and alveoli in chronic airway obstruction: A clinicopathologic study. American Review of Respiratory Disease 114: 137-145, July 1976. MITTMANN, C. The PiMZ phenotype: Is it a significant risk factor for the development of chronic obstructive lung disease? American Review of Respiratory Disease 118(4): 649-652, October 1978. MONSON, R.R. Occupational Epidemiology. Boca Raton, Florida, CRC Press, Inc., 1980. MORRIS, J.F., KOSKI, A.. JOHNSON, L.C. Spirometric standards for healthy nonsmoking adults. American Review of Respiratory Disease 103(1): 57-67, January 1971. MORSE, J.O. Alpha:-antitrypsin deficiency. New England Journal of Medicine 299(19): 1045-1048, November 9, 1978 and 299(20): 1099-1105, November 16, 1978. MUELLER, R.E., KEBLE, D.L., PLUMMER, J., WALKER, S.H. The prevalence of chronic bronchitis, chronic airway obstruction, and respiratory symptoms in a Colorado city. American Review of Respiratory Disease 103(2). 209-228, February 1971. MUELLER, W.H., CHAKRABORTY, R. BARTON, S.A., ROTHHAMMER, F., SCHULL, W.J. Genes and epidemiology in anthropological adaptation studies: Familial correlations in lung function in populations residing at different altitudes in Chile. Medical Anthropology 4(3): 367-384, Summer 1980. MULTIPLE RISK FACTOR INTERVENTION TRIAL RESEARCH GROUP. Risk factor changes and mortality results. Journal of the American Medical Association 248(12): 1465-1477, September 24, 1982. NADEL, J.A., COMROE, J.H., Jr. Acute effects of inhalation of cigarette smoke on airway conductance. Journal of Applied Physiology 16(4). 713-716, July 1961. NATIONAL CENTER FOR HEALTH STATISTICS. Vital and Health Statistics Series No. 136. DHHS Publication No. (PHS) 81-1564, 1981. NATIONAL CENTER FOR HEALTH STATISTICS. Unpublished data. NEMERY, B., MOAVERO, N.E., BRASSEUR, L., STANESCU, D.C. Significance of small airway tests in middle-aged smokers. American Review of Respiratory Disease 124(3): 232-238, September 1981. NERI, L.C.. MANDEL, J.S., HEWITT, D., JURKOWSKI, D. Chronic obstructive pulmonary disease in two cities of contrasting air quality. Canadian Medical Association Journal 113(11): 1043-1046, December 13, 1975. NEUBURGER, N., LEVISON, H., KRUGER, K. Transit time analysis of the forced expiratory vital capacity in cystic fibrosis. American Review of Respiratory Disease 114(4): 753-759, October 1976. NEUKIRCH, F., LIARD, R., COOREMAN, J., PERDRIZET, S. Prevalence of respira- tory symptoms in Parisian teenagers according to smoking habits. Journal of Epidemiology and Community Health 36(3): 202-204, September 1982. O'DONNELL, T.V., DE HAMEL, F. Objective respiratory screening among Dunedin public servants. New Zealand Medical Journal 84: 99-103, August 11, 1976. OGILVIE, A.G., STRANG, C., LEGGAT, P.O., NEWELL, D.J. A Ten-Year Prospective Study of Chronic Bronchitis tn the North-East of England. Edinburgh, Churchill Livingstone, 1973. ORELL, S.R., MAZODIER, P. Pathological findings in a,-antitrypsin deficiency. In: Mittman, C. (Editor). Pulmonary Emphysema and Proteolysis. New York, Academic Press, 1972, pp. 69-88. ORIE, N.G., SLUITER, H.J., DeVRIES, K., TAMMELING, G.J., WITKOP, J. The host factor in bronchitis. In: Orie, N.G.M., Sluiter, H.J. (Editors). Bronchitis, An international Symposium, April 27-29, 1960. Assen, Netherlands, Charles C Thomas, Royal Vangorcum, 1961, pp. 43-59. OSMAN, M., CANTOR, J., ROFFMAN, S., TURINO, G.M., MANDL, I. Tobacco smoke exposure retards elastin repair in experimental emphysema. American Review of Respiratory Disease 125(4): 213A, April 1982. OXHOJ, H., BAKE, B., WILHELMSEN, L. Spirometry and flow-volume curves in 10- year follow-up in men born 1913. Scandinavian Journal of Respiratory Diseases 57(6): 310-312, 1976. PARE, P.D., BROOKS, L.A., BATES, J., LAWSON, L.M., NELEMS, J.M.B., WRIGHT, J.L., HOGG, J.C. Exponential analysis of the lung pressure-volume curve asa predictor of pulmonary emphysema. American Review of Respiratory Disease 126(1): 54-61, July 1982. PARK, SS., JANIS, M., SHIM, C.S., WILLIAMS, M.H., Jr. Relationship of bronchitis and emphysema to altered pulmonary function. American Review of Respiratory Disease 102(6): 927-936, December 1970. PARK, S.S., KIKKAWA, Y., GOLDRING, LP., DALY, MLM., ZELEFSKY, M., SHIM, C., SPIERER, M., MORITA, T. An animal model of cigarette smoking in beagle dogs: Correlative evaluation of effects on pulmonary function, defense, and morphology. American Review of Respiratory Disease 115(6): 971-979, June 1977. PARK, T.K. Cigarette smoking patterns among students attending a Christian university in Seoul, Korea. Yonsei Medical Journal 22(2): 145-154, 1981. PERMUTT, S., MENKES, H.A. Spirometry. Analysis of forced expiration within the time domain. In: Macklen, P.T., Permutt, S. (Editors). The Lung in the Transition Between Health and Disease. New York, Marcel Dekker, 1979, pp. 113-152. PETO, R., SPEIZER, F.E., COCHRANE, A.L., MOORE, F., FLETCHER, C.M., TINKER, C.M., HIGGINS, LT.T., GRAY, R.G., RICHARDS, S.M., GILLILAND, J., NORMAN-SMITH, B. The relevance in adults of air-flow obstruction, but not of mucus hypersecretion, to mortality from chronic lung disease: Results from 20 years of prospective observation. American Review of Respiratory Disease 128(3): 491-500, September 1983. PETTY, T.L., PIERSON, DWJ., DICK, N.P., HUDSON, L.P., WALKER, S.H. Follow-up evaluation of a prevalence study for chronic bronchitis and chronic airway obstruction. American Review of Respiratory Disease 114(3): 881-890, November 1976. PETTY, T.L., RYAN, SF, MITCHELL, RS. Cigarette smoking and the lungs: Relation to postmortem evidence of emphysema, chronic bronchitis and black lung pigmentation. Archives of Environmental Health 14: 172-177, January 1967. 179 PETTY, T.L., SILVERS, G.W., STANFORD, R.E. Functional correlations with mild and moderate emphysema in excised human lungs. American Review of Respira- tory Disease 125(6): 700-704, December 1981. POUKKULA, A., HUHTI, E., MAKARAINEN, M. Chronic respiratory disease among workers in a pulp mill. A ten-year follow-up study. Chest 81(3): 285-289, March 3, 1982. QIZILBASH, A., YOUNG-PONG, O. Alpha.-antitrypsin liver disease in differential diagnosis of PAS-positive, diastase-resistant globules in liver cells. American Journal of Clinical Pathology 7X6): 697-702, June 1983. RAWBONE, R.G., KEELING, C.A., JENKINS, A., GUZ, A. Cigarette smoking among secondary school children in 1975. Prevalence of respiratory symptoms, knowledge of health hazards, and attitudes to smoking and health. Journal of Epidemiology and Community Health 32(1): 53-58, March 1978. REID, L.M. Pathology of chronic bronchitis. Lancet 1(6806): 275-278, February 6, 1954. ROBERTSON, D.G., WARREL, D.A., NEWTON-HOWES, J.S., FLETCHER, C.M. Bronchial reactivity to cigarette and cigar smoke. British Medical Journal (5665). 269-271, August 2, 1969. ROKAW, S.N., DETELS, R., COULSON, A.H., SAYRE, J.W., TASHKIN, D.P., ALLWRIGHT, S.S., MASSEY, F.J., Jr. The UCLA population studies of chronic obstructive respiratory disease. 3. Comparison of pulmonary function in three communities exposed to photochemical oxidants, multiple primary pollutants, or minimal pollutants. Chest 78: 252-262, August 1980. RYAN, S.F., VINCENT, T.N., MITCHELL, R.S., FILLEY, G.F., DART, G. Ductectasia: An asymptomatic pulmonary change related to age. Medicina Thoracalis 22(2): 181-187, 1965. RYDER, R.C., DUNNILL, M.S., ANDERSON, J.A. A quantitative study of bronchial mucous gland volume emphysema and smoking in a necropsy population. Journal of Pathology 104(1): 59-71, May 1971. RYDER, R.C., THURLBECK, W.M., GOUGH, J. A study of the interobserver variation in the assessment of the amount of pulmonary emphysema in paper- mounted whole lung sections. American Review of Respiratory Disease 99: 354-364, March 1969. SALMON, R.B., SAIDEL, G.M., INKLEY, S.R., NIEWOEHNER, D.E. Relationship of ventilation inhomogeneity to morphologic variables in excised human lungs. American Review of Respiratory Disease 126(4): 686-690, October 1982. SAMET, J.M. A historical and epidemiologic perspective on respiratory symptoms questionnaires. American Journal of Epidemiology 1086): 435-446, December 1978. SAMET, J.M., SCHRAG, S.D., HOWARD, C.A., KEY, C.R., PATHAK, D.R. Respira- tory disease in a New Mexico population sample of Hispanic and non-Hispanic whites. American Review of Respiratory Disease 125(2): 152-157, February 1982. SAMET, J.M., TAGER, I.B., SPEIZER, F.E. The relationship between respiratory illness in childhood and chronic air-flow obstruction in adulthood. American Review of Respiratory Disease 127(4): 508-523, April 1983. SARIC, M., LUCIC-PALAIC, S., HORTON, R.J.M. Chronic nonspecific lung disease and alcohol consumption. Environmental Research 14(1): 14-21, August 1977. SAWICKI, F. Regression Persistence and Incidence of Chronic Bronchitis in a Sample of an Urban Population Followed Up for 5 Years. Presented at the 8th International Scientific Meeting of the International Epidemiological Association, Puerto Rico, September 1977. SCHENKER, M.B., SAMET, J.M., SPEIZER, F-.E. Effect of cigarette tar content and smoking habits on respiratory symptoms in women. American Review of Respira- tory Disease 125(6): 684-690, June 1982. SCHILLING, R.S.F., LETAI, A.D., HUI, S.L., BECK, G.J.. SCHOENBERG, J.B., BOUHUYS, A. Lung function, respiratory disease, and smoking in families. American Journal of Epidemiology 106(4): 274-283, October 1977. 180 SCHLESINGER, Z., GOLDBOURT, U., MEDALIE, J.H., RISS, E., NEUFELD, H.N., ORON, D. Pulmonary function and respiratory disease among adult male Israelis. Variations by age and birth place. Israel Journal of Medical Sciences 8(7): 957-964, July 1972. SCHUYLER, M.R., RYNBRANDT, D.J., KLEINERMAN, J. Physiologic and morpho- logic observations of the effects of intravenous elastase on the lung. American Review of Respiratory Disease 117(1): 97-102, January 1978. SEELY, J.E., ZUSKIN, E., BOUHUYS, A. Cigarette smoking: Objective evidence for lung damage in teen-agers. Science 172(3983): 741-743, May 14, 1971. SHARP, J.T., PAUL, O., LEPPER, M.H., McKEAN, H., SAXON, G.A., Jr. Prevalence of chronic bronchitis in an American male urban industrial population. American Review of Respiratory Disease 91(4): 510-520, April 1965. SHARP, J.T., PAUL, O., McKEAN, H., BEST, W.R. A longitudinal study of bronchitic symptoms and spirometry in a middle-aged, male, industrial population. American Review of Respiratory Disease 108(5): 1066-1077, November 1973. SILVERS, G.W., PETTY, T.L., STANFORD, R.E. Elastic recoil changes in early emphysema. Thorax 35: 490-495, July 1980. SIMONSSON, B. Effect of cigarette smoking in the forced expiratory flow rate. American Review of Respiratory Disease 85: 543-539, 1962. SLUIS-CREMER, G.K., SICHEL, H.S. Ventilatory function in males in a Witwaters- rand town. Comparison between smokers and nonsmokers. American Review of Respiratory Disease 98(2): 229-239, August 1968. SOBOL, BJ., VAN VOORHIES, L., EMIRGIL, C. Detection of acute effects of cigarette smoking on airway dynamics: A critical and comparative study of pulmonary function tests. Thorax 32(3): 312-216, June 1977. SPAIN, D.M., SIEGEL, H., BRADESS, V.A. Emphysema in apparently healthy adults. Smoking, age, and sex. Journal of the American Medical Association 224(3): 322- 325, April 16, 1973. SPARROW, D., ROSNER, B., COHEN, M., WEISS, S.T. Alcohol consumption and pulmonary function. A cross-sectional and longitudinal study. American Review of Respiratory Disease 127(6): 735-738, June 1983a. SPARROW, D., STEFOS, T., BOSSE, R., WEISS, S.T. The relationship of tar content to decline in pulmonary function in cigarette smokers. American Review of Respiratory Disease 127(1): 56-58, January 1983b. SPEIZER, F.E., TAGER, I.B. Epidemiology of chronic mucus hypersection and obstructive airways disease. Epidemiologic Reviews 1: 124~142, 1979. STANESCU, D.C., VERITER, C., FRANS, A., BRASSEUR, L. Maximal expiratory flow rates and “closing volume” in asymptomatic healthy smokers. Scandinavian Journal of Respiratory Disease 54(4): 264-271, 1973. STEBBINGS, J.H., Jr. Chronic respiratory disease among nonsmokers in Hagerstown, Maryland. III. Social class and chronic respiratory disease. Environmental Research 4(3): 213—232, August 1971. STERLING, G.M. Mechanism of bronchoconstriction caused by cigarette smoking. British Medical Journal 35560): 275-277, July 29, 1967. STUART-HARRIS, C.H. Chronic bronchitis (Part I. Abstracts of World Medicine 42(9): 649-669, September 1968a. STUART-HARRIS, C.H. Chronic bronchitis (Part II). Abstracts of World Medicine 42(10): 737-751, October 1968b. SUTINEN, S., VAAJALAHTI, P., PAAKKO, P. Prevalence, severity, and types of pulmonary emphysema in a population of deaths in a Finnish city. Correlation with age, sex and smoking. Scandinavian Journal of Respiratory Disease 592): 101-115, April 1978. SYMONDS, G., RENZETTI, A.D., Jr., MITCHELL, M.M. The diffusing capacity in pulmonary emphysema. American Review of Respiratory Disease 1093): 391-393, March 1974. 181 TAGER, I.B., ROSNER, B., TISHLER, P.V., SPEIZER, F.E., KASS, E.H. Household aggregation of pulmonary function and chronic bronchitis. American Review of Respiratory Disease 114(3): 485-492, September 1976. TAGER, LB., SPEIZER, F.E. Risk estimates for chronic bronchitis in smokers: A study of male-female differences. American Review of Respiratory Disease 113(5): 619- 625, May 1976. TAGER, L, TISHLER, P.V., ROSNER, B., SPEIZER, F.E., LITT, M. Studies of the familial aggregation of chronic bronchitis and obstructive airways disease. International Journal of Epidemiology 7(1): 55-62, March 1978. TATTERSALL, S.F., BENSON, M.K., HUNTER, D., MANSELL, A., PRIDE, N.B., FLETCHER, C.M. The use of tests of peripheral lung function for predicting future disability from airflow obstruction in middle-aged smokers. American Review of Respiratory Disease 118(6): 1035-1050, December 1978. TATTERSALL, S.F., PEREIRA, R.P., HUNTER, D., BLUNDELL, G., PRIDE, N.B. Lung distensibility and airway function in intermediate alpha.-antritrypsin deficiency (PiMZ). Thorax 34(5): 637-646, October 1979. THURLBECK, W.M. A clinico-pathological study of emphysema in an American hospital. Thorax 18(1): 59-67, March 1963. THURLBECK, W.M. The diagnosis of emphysema. Thorax 16): 571-574, November 1964. THURLBECK, W.M. Internal surface area and other measurements in emphysema. Thorax 226): 483-496, November 1967a. THURLBECK, W.M. The internal surface area of nonemphysematous lungs. Amert- can Review of Respiratory Disease 95(5): 765-773, May 1967b. THURLBECK, W.M. Chronic Airflow Obstruction in Lung Disease. Major Problems in Pathology, Volume 5. Philadelphia, W.B. Saunders Company, 1976, 456 pp. THURLBECK, W.M. Aspects of chronic airflow obstruction. Chest 72(3): 341-349, September 1977. THURLBECK, W.M. Post-mortem lung volumes. Thorax 34(6): 735-739, December 1979. THURLBECK, W.M. Overview of the pathology of pulmonary emphysema in the human. Clinics in Chest Medicine 4(3): 337-350, September 1983. THURLBECK, W.M., DUNNILL, M.S., HARTUNG, W., HEARD, B.E., HEPPLE- STON, A.G., RYDER, R.C. A comparison of three methods of measuring emphyse- ma. Human Pathology 1(2): 215-226, June 1970. THURLBECK, W.M., RYDER, R.C., STERNBY, N. A comparative study of the severity of emphysema in necropsy populations in three different countries. American Review of Respiratory Disease 102): 239-248, February 1974. TOBIN, M.J., COOK, P.J.L., HUTCHISON, D.C.S. Alpha:-antitrypsin deficiency: The clinical features and physiological features of pulmonary emphysema in subjects homozygous for Pi type Z. A survey by the British Thoracic Association. British Journal of Diseases of the Chest 77: 14-27, January 1983. TOCKMAN, MSS. Follow-up Study of Pulmonary Function in Nonsmokers. Doctoral ~ Dissertation, The Johns Hopkins University, Baltimore. Ann Arbor, University Microfilms International, Thesis No. 79-24643, 1979, 650 pp. TOCKMAN, M., MENKES, H., COHEN, B., PERMUTT, S., BENJAMIN, J., BALL, W.C., Jr., TONASCIA, J. A comparison of pulmonary function in male smokers and nonsmokers. American Review of Respiratory Disease 114(4): 711-720, October 1976. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE. Smoking and~ Health: A Report of the Surgeon General. US. Department of Health, Education, and Welfare, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health, DHEW Publication No. (PHS)79-50066, 1979, 1136 PP- 182 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. The Health Conse- quences of Smoking for Women: A Report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Heaith, 1980a, 359 pp. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. Report of Task Force on Epidemiology of Respiratory Disease. State of Knowledge, Problems, Needs, July 1979. Public Health Service, National Institutes of Health, NIH Publication No. 81-2019, October 1980b. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. The Health Conse- quences of Smoking. The Changing Cigarette: A Report of the Surgeon General. US. Department of Health and Human Services, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health, DHHS Publication No. (PHS)81-50156, 1981, 269 pp. U.S. PUBLIC HEALTH SERVICE. Smoking and Health. Report of the Advisory Committee to the Surgeon General of the Public Health Service. U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, PHS Publication No. 1103, 1964, 387 pp. U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. A Report of the Surgeon General, 1971. U.S. Department of Health, Education, and Welfare, Public Health Service, Health Services and Mental Health Administration. DHEW Publication No. (HSM)71-7513, 1971, 458 pp. U.S. PUBLIC HEALTH SERVICE. Prevalence of Selected Chronic Respiratory Conditions, United States, 1970. Vital and Health Statistics data from the National Health Survey, Series 10, Number 84, September 1973. VAN DER LENDE, R., KOK, T.J., PESET REIG, R., QUANJER, Ph.H., SCHOUTEN, J.P., ORIE, N.G.M. Decreases in VC and FEVi, with time: Indicators for effects of smoking and air pollution. Bulletin Europeen de Physiopathologie Respiratoire 17(5): 775-792, September—October 1981. WALTER, S., NANCY, N.R., COLLIER, C.R. Changes in the forced expiratory spirogram in young male smokers. American Review of Respiratory Disease 1195): 717-724, May 1979. WEBSTER, P.M., LORIMER, E.G., MAN, S.F.P., WOOLF, C.R., ZAMEL, N. Pulmo- nary function in identical twins: Comparison of nonsmokers and smokers. American Review of Respiratory Disease 11%2): 223-228, February 1979. WEISS, S.T., TAGER, I.B., SCHENKER, M., SPEIZER, F.E. The health effects of involuntary smoking. American Review of Respiratory Disease 128(5): 933-942, November 1983. WILHELMSEN, L., ORHA, I., TIBBLIN, G. Decrease in ventilatory capacity between ages 50 and 54 in a representative sample of Swedish men. British Medical Journal 3(5670): 553-556, September 6, 1969. WOOLCOCK, A.J., COLMAN, M.H., BLACKBURN, C.R.B. Chronic lung disease in Papua New Guinea and Australian populations. Papua New Guinea Medical Journal 16(1): 29-35, March 1973. WOOLCOCK, A.J., VINCENT, N.J., MACKLEM, P.T. Frequency dependence of compliance as a test for obstruction in the small airways. Journal of Clinical Investigation 48(6): 1097-1106, June 1969. WOOLF, C.R., SUERO, J.T. The respiratory effects of regular cigarette smoking in women. American Review of Respiratory Disease 103(1): 26-37, January 1971. WOOLF, C.R., ZAMEL, N. The respiratory effects of regular cigarette smoking in women. A five-year prospective study. Chest 78(5): 707-713, November 1980. ZAMEL, N., YOUSSEF, H.H., PRIME, F.J. Airway resistance and peak expiratory flow rate in smokers and nonsmokers. Lancet 1: 1237-1238, 1963. 183 CHAPTER 3. MORTALITY FROM CHRONIC OBSTRUCTIVE LUNG DISEASE DUE TO CIGARETTE SMOKING 185 CONTENTS Introduction COLD Mortality Patterns in the United States Prospective Studies The British Doctors Study The American Cancer Society 25-State Study The U.S. Veterans Study The Canadian Veterans Study The American Cancer Society 9-State Study California Men in Various Occupations The Swedish Study The Japanese Study of 29 Health Districts Cigarette Smoking and Overall COLD Mortality Retrospective Studies Male and Female Differences in COLD Mortality Amount Smoked and Mortality From COLD Inhalational Practice and Mortality From COLD Age of Initiation and COLD Mortality Smoking Cessation and COLD Mortality Pipe and Cigar Smoking Mortality From COLD International Comparison of COLD Death Rates a Smoking Habits: The Emigrant Studies COLD Mortality Among Populations With Low S Rates Summary and Conclusions References Introduction The chronic obstructive lung diseases (COLD) that are causally related to cigarette smoking are chronic bronchitis, emphysema, and chronic obstructive pulmonary disease and allied conditions without mention of asthma, bronchitis, or emphysema. The last classification was introduced by the National Center for Health Statistics in response to the changes that occurred in the late 1960s in patterns of reporting causes of death on death certificates. During this period, physicians increasingly recorded deaths as due to “chronic obstruc- tive lung disease” rather than the more specific categories of “emphysema” or “chronic bronchitis” (NCHS 1982). Because of this shift in patterns of reporting, and in recognition of the difficulty of clinically separating these categories from one another as a cause of death, the discussion in this chapter combines all of these categories for analysis, where possible, which should result in a more complete description of death rates from COLD. COLD Mortality Patterns in the United States The three chronic obstructive lung diseases related to smoking may account for almost 62,000 deaths in 1983, compared with 56,920 deaths in 1982, according to provisional mortality data recently published by the National Center for Health Statistics. This data is based on a 10 percent sample of all death certificates for the 12- month period ending in November (NCHS 1984). This is a dramatic increase from 1970, when slightly over 33,000 deaths were attributed to COLD. Complete mortality data are available through 1980, and Table 1 presents the numbers of male and female deaths from COLD for 1970, 1975, and 1980. In addition to the relatively rapid rise in COLD deaths during these years, there was also a shift in the male to female ratio of these deaths. In 1970 male deaths outnumbered female deaths by a ratio of 4.3 to 1. By 1980 this ratio had declined to 2.36. The age-adjusted death rates for COLD during the years 1960 through 1980 are presented in Figure 1 for white men, white women, and men and women of other races. As described in the previous chapter, however, COLD is a slowly progressive disease, and death from COLD usually occurs only after extensive damage has devel- oped in the diseased lungs. Many individuals with COLD will die with their disease rather than because of it, and even those who do die of COLD are usually symptomatic for an extended period of time prior to death. Therefore, death rate data may not accurately reflect the true prevalence or incidence of COLD in the U.S. population. In addition, COLD is often not recorded as a cause of death in hospital records 189 TABLE 1.—Number of and ratio of male to female chronic obstructive lung disease (COLD) deaths for three time periods, United States 1970 1975 1980 Cause of death Men Women Men Women Men Women Chronic bronchitis 4,282 1,564 3,260 1,452 2,380 1,348 Emphysema 18,901 3,820 14,849 3,946 10,133 3,744 COLD and allied conditions 3,601 848 13,411 4,182 24,820 10,734 Total COLD deaths 26,784 6,227 31,520 9,580 37,333 15,826 M:F ratio 4.30 3.29 2.36 SOURCE: National Center for Health Statistics (1982, and unpublished mortality data). 30- a5 wuire 3 S 20 o oS S OTHERS a «1 5F id a. ded a x 10 WHITE? 4 5b OTHER i i i J 1960 1965 1970 1975 1980 YEAR FIGURE 1.—Age-adjusted COLD mortality rates for whites and nonwhites in the United States, 1960-1980 SOURCE: National Center for Health Statistics (1982, and unpublished data). (Moriyama et al. 1966) or on death certificates (Mitchell et al. 1968), even though it may have played an important role in a person’s death. In a recent prospective study, nearly half of the excess mortality associated with significantly lowered FEV, was attributed to other causes (Peto et al. 1983). Relatively advanced lung disease (as judged by pathologic examination) may also exist without clinical 190 recognition because of the lung’s large ventilatory reserve (Mitchell et al. 1968; Hepper et al. 1969). A joint committee of the American College of Chest Physicians and the American Thoracic Society (ACCP-ATS 1975) has developed standardized definitions of these conditions that may improve the accuracy of mortality reporting in the future. As discussed in the chapter on morbidity in this Report, COLD in an individual is usually a combination of mucus hypersecretion, airway narrowing, and emphysema. The extent of damage represent- ed by each of these three processes can vary substantially from individual to individual, both in the absolute magnitude of the damage and in the proportional contribution of each of these three components. The majority of those with smoking-induced lung damage do not have enough damage to result in clinically significant disease, and only some of those with clinically significant disease have damage to the lung that results in death from COLD. The progressive loss of FEV, in smokers described in the preceding chapter is one measure of the extent and progression of lung damage, and individuals with a markedly reduced FEV, are far more likely to die of COLD (Peto et al. 1983). These deaths commonly occur secondary to the failure of these severely damaged lungs to carry out the gas exchange required for survival. Because death from COLD is the end result of lung damage accumulated over many years, these deaths would be expected to occur disproportionately in the older age groups; therefore, the presentation of a single age-adjusted death rate might not reflect a true picture of the changes in this disease with time. Figure 2 presents the age-specific death rates in 1977 for COLD in the different sexes and racial groups. Death rates increase rapidly over the age of 45, and this increase is particularly dramatic over the age of 65. In addition, the bulk of the difference between white men and men of other races, evident in Figure 2, occurs in those over age 65. Indeed, the COLD death rates for nonwhite men are actually higher than that for white men under age 55. The examination of age-specific death rates over time also presents a somewhat different picture from that presented by the age- adjusted numbers in Figure 1. The age-adjusted rates for white men in Figure 1 seem to have changed only slightly between 1968 and 1980. However, when the age-specific rates for the years 1968 and 1977 are examined (Figure 3), this apparent stability can be seen to be a product of counterbalancing trends in those under and over 65 years of age. The death rates from COLD declined in white men under age 65 between 1968 and 1977, but COLD death rates increased in white men over age 65 during the same years; this increase was particularly dramatic in those over age 75. 191 WHITES 400 oS © 300 fom] oS a a ws 200+ OTHERS. << Cc roy WHITES OTHER 25-34 35-44 46-54 55-64 65-74 75-84 85+ AGE FIGURE 2.—Age-specific COLD mortality rates for whites and nonwhites in the United States, 1977 SOURCE: National Center for Health Statistics (1982). Figure 4 presents the age-specific COLD mortality rates for white women in 1960, 1968, and 1977. As with the male rates, the female COLD death rates rise rapidly with age, but they are substantially lower than the male rates. In contrast with the male rates, however, the white female death rates increased steadily with time from 1960 through 1977 both above and below age 65. In each of the age groups over the age of 45, where significant numbers of COLD deaths would be expected, there was a steady increase in rates from 1960 to 1968 and from 1968 to 1977. As is discussed later in this chapter, these differences between men and women over time are consistent with their differences in smoking behavior. The effect of the normal aging process on the lung is small, rarely limits maximal exercise, and never results in ventilatory failure. Therefore, death from chronic obstructive lung disease is never a natural part of the aging process; it is the result of an infectious or other disease process or of the cumulative damage of environmental respiratory toxins. The most important of these toxins in the United States is cigarette smoke. 192 1977 400+ S © 300+ 1968 So So oc La a mw 200+ < co 100} 1960 25-34 35-44 45-54 55-64 65-74 75-84 85+ AGE FIGURE 3.—Age-specific COLD mortality rates for white men in the United States, 1960, 1968, and 1977 SOURCE: National Center for Health Statistics (1982). In spite of the large ventilatory reserve possessed by the lung, death from COLD is a major cause of U.S. mortality. This mortality is closely linked to cigarette smoking and has been examined extensively. Figure 5 shows the differences in COLD death rates for smokers and nonsmokers at different ages. From the rarity of COLD death in nonsmokers and the magnitude of the increased risk associated with smoking, it is clear that the overwhelming impor- tance of cigarette smoking as a determinant of abnormal lung function demonstrated in the previous chapter is matched by the importance of cigarette smoking as a determinant of death from COLD. Examination of the death rates from COLD in smokers and nonsmokers suggests that from 85 to 90 percent of the COLD deaths in the United States can be attributed to cigarette smoking. Prospective Studies The relationship between smoking and death from COLD has been evaluated in a large number of prospective mortality studies. There are eight major prospective studies of the disease consequences of smoking. They involve large numbers of smokers and nonsmokers 193 1977 80+ 7O-+ 1968 60} 50+ 40+ 1960 RATE PER 100,000 20+ 10+ L L. 1. —4 25-34 35-44 45-54 55-64 65-74 75-84 86+ AGE FIGURE 4.—Age-specific COLD mortality rates for white women in the United States, 1960, 1968, and 1977 SOURCE: Nationa! Center for Health Statistics (1982) and have examined the death rates from COLD in both groups. These studies cumulatively represent more than 17 million person- years of observation and over 330,000 deaths. The size of the populations studied allows a detailed examination of the relationship between smoking and death rates. The characteristics of the populations studied are summarized in Table 2 and are briefly reviewed here. The British Doctors Study The British doctors study (Doll and Hill 1954, 1956, 1964a, 1964b, 1966; Doll and Peto 1976, 1977; Doll and Pike 1972; Doll et al. 1980) of 40,000 male and female physicians in Britain was the first prospective study and is the longest running. Deaths from chronic bronchitis and emphysema were combined. Deaths from cor pulmo- nale (i.e., heart failure secondary to lung disease) were separately analyzed by smoking category and probably include some deaths from chronic bronchitis and emphysema. 194 450 Smoker 400 oo LY S 300 so : & | ~ | o | & | 2 200 1 = i 100 Nonsmoker o 4 + eS | 35-44 45-54 55-64 65-74 75-84 Age Group FIGURE 5.—Death rate for bronchitis, emphysema, or both, per 100,000 population, by age and smoking status', U.S. veterans study, 16-year followup ‘Smoker is defined as al! people who smoke cigarettes and those who have ever smoked other tobacco products SOURCE: Adapted from Rogot and Murray (1980) The American Cancer Society 25-State Study The American Cancer Society 25-State study (Hammond 1965, 1966; Hammond and Garfinkel 1969; Hammond et al. 1976; Lee and Garfinkel 1981) represents the largest investigation. Deaths from emphysema were separately analyzed by smoking habit; deaths from cor pulmonale were also separately recorded. The U.S. Veterans Study The mortality experience of approximately 294,000 U.S. veterans who held U.S. Government life insurance policies in December 1953 was examined in the U.S. veterans study (Dorn 1959; Kahn 1966; Rogot 1974a, b; Rogot and Murray 1980). Deaths from COLD were recorded as “bronchitis and/or emphysema”; “bronchitis, underlying or contributory”; and “emphysema without bronchitis.” The Canadian Veterans Study Initiated in 1955 by the Canadian Department of National Health and Welfare, the Canadian veterans study (Best 1966; Best et al. 1961) included 78,000 men and 14,000 women. Over the next 6 years of followup, there were 9,491 male and 1,794 female deaths. The cause of death in most of these cases was confirmed by autopsy. 195 96T TABLE 2 .— Outline of eight major prospective studies Doll Weir Cedertof : Dorn Best . Authors mul Hammond Kahn Hirayama Jone Hammond Dunn Friberg Peto t Walker Horn Linden Hrubec Pike Breslow Lorich Males and Total population . . Probability California British females US of Canadian White males in sample of Subjects doctors n veterans = healt " various the 3 distnets in pensioners nine States occupations Swedish States Japan Pe population Population size 40,000 1,000,000 230,000 265,000 92,000 187,000 68,000 55,000 Females 6,000 562,671