Tg TABLE 2.—Continued Author, year, country Population Cough Phlegm Other Comments Higgins et al., 4,699 men and Chronic bronchitis Chronic bronchitis (cough and 1977, women, aged Men phlegm >3 mo/yr); chronic US. 20-74, Tecumseh NS 5.1 bronchitis increased with age EX 26 for male smokers; no age trend 5M apparent for male or female <20/day 13.4 nonsmokers; dose-response > 20/day 29.9 relationship between chronic Pipe/cigar 8.4 bronchitis and cigarette smoking (age adjusted) Women NS 35 EX 47 SM < 20/day 48 > 20/day 15.3 as TABLE 2.—Continued Author, year, country Population Cough Phlegm Other Comments Lebowitz and 2,857 men and Chronic cough and/or phlegm Male prevalence consistently Burrows, women, aged 14-96, Men greater than female only in older 1977, US. Tucaon NS 10.3 age groups; frequency of SM (pack years) symptoms increased with age; <6 29.0 impossible to distinquish effects 6-20 35.8 of aging and increased duration 21-40 47.9 of smoking 41+ 61.1 Women NS 12.1 SM (pack-years) <6 21.0 6-20 33.1 21-40 40.5 41+ 60.4 &¢ TABLE 2.—Continued Author, year, country Population Cough Phlegm Other Comments Bland et al., 6,320 first-year Morning cough Breathlessness No questions on phlegm; child’s 1978, secondary school Boys Boys smoking habits more important Great Britain children, NS 3.1 NS 12 than parents’ smoking habits; Derbyshire SM once 29 SM once 14 Parents’ smoking habits Occas. 4.0 Occas. 22 independently related to most 1 per wk. 19.2 1 per wk 35 symptom frequencies for boys and girls Girls Girls NS 18 NS 7 SM once 45 SM once 22 Occas. 6.0 Occas. 29 1 per wk. 13.5 lperwk. 40 Cough at other times Boys NS 20 SM once 27 Occas, 34 1 per wk. 47 Girls NS 19 SM once 30 Occas. 35 1 per wk. 47 ¥S TABLE 2.—Continued Author, year, country Population Cough Phlegm Other Comments Huhti et al., 1,162 men, All day in winter All day in winter Chronic bronchitis For total group, significant 1978, aged 25-65, Age NS NS Age NS increase with age of cough, Finland Hankasalmi 25-39 2 5 25-39 9 phlegm, and severe breathlese- 40-49 2 2 40-49 2 ness; for nonsmokers, signficant 50-59 5 8 50-59 15 increase with age for phlegm 60-69 4 7 60-69 19 and breathlessness only Age EX EX EX 25-39 = 11 25-39 11 40-49 - 10 40-49 14 50-59 4 8 50-59 ll 60-69 12 18 60-69 28 Age SM SM SM 1-14 g/day 26-39 9 14 25-39 29 40-49 19 29 40-49 39 50-59 19 24 50-59 31 60-69 30 7 60-69 39 SM 15-24 g/day 25-39 13 40-49 45 50-59 46 60-69 46 SM >25 g/day 25-39 50 40-49 63 50-59 57 60-69 53 g¢ TABLE 2.—Continued Author, year, country Population Cough Phlegm Other Comments Manfreda et al., 273 men and 229 Most days >3 mo/yr Most days >3 mo/yr Wheeze apart from colds No consistent difference in 1978 women, aged Men symptom prevalence for two Canada 24-55, two CH* PLP* CH PLP CH PLP communities; higher prevalence communities NS 8.3 4.0 NS _ 4.0 NS 4.2 8.0 of cough, phlegm, and wheeze in Manitoba EX 8.1 29 EX 108 5.7 EX 108 14.3 among smokers than SM 25.4 31.5 SM 169 247 SM 268 31.5 nonsmokers or ex-smokers; * CH=Charleswood Women ** PLP=Portage la Prairie NS — 40 NS — 4.0 NS 35 8.0 Ex — 10.0 EX — 5.0 EX 121 20.0 SM 203 31.7 SM 102 26.4 SM 254 302 TABLE 2.—Continued Author, year, country Population Cough Phlegm Other Comments Rawbone et al., 10,498 secondary A little most days With colds Frequent colds * EXPER (ex-emokers and 1978, echool children, Age NS NS NS experimental smokers combined); Great Britain aged 11-17, li 64 22.8 36.0 sex differences not significant; Hounslow 13 16.7 25.3 32.3 nonstandard questions; higher 15 13.4 24.5 34.3 symptom prevalence in younger EXPER * EXPER EXPER children not explained 11 20.5 32.3 42.2 13 173 31.2 36.1 15 11.3 29.6 36.3 SM SM SM ll 24.3 56.1 51.1 13 25.9 49.6 50.4 15 27.4 53.6 39.8 A little every day NS 11 13 13 42 15 47 EXPER 11 70 13 47 15 3.5 SM 11 29.2 13 17.8 15 13.4 Lg TABLE 2.—Continued Author, year, country Population Cough Phiegm Other Comments Bouhuys et al., 7,203 residents, Usual cough Smoking significantly associated 1979, aged 7-65+, LE* AN** WIt with cough, phlegm, wheeze, and US. three communities Men dyspnea; prevalence increased NS 8 100 15 significantly with age, slightly SM 27 324 higher in urban community; Women women had lower prevalence of NS 7 12 9 phlegm and higher prevalence of SM 13 17 uw dyspnea than men * LE= Lebanon ** AN= Ansonia t WI = Winnsboro Burghard et. al., 29,138 students, Morning Breathlessness Prevalence of symptoms increased 1979, aged 14-18, NS 13.7 NS 14.1 with increasing cigarette France Bas-Rhin Department SM 25.7 SM 22.2 consumption; girls had higher Day or night prevalence of respiratory NS 16.9 symptoms for each smoking SM 29.1 category Chronic NS 2.7 SM 6.6 g¢ TABLE 2.—Continued Author, year, country Population Cough Phlegm Other Comments Gulsvik, 19,988 people, Morning cough When coughing Cough and phlegm periods Cough and phlegm increased more 1979, aged 15-70, NS ll NS 10 NS 6 with age for smokers (10-19 Norway Oslo EX 15 EX 18 EX 8 cig/day) than nonsmokers; no SM 36 SM 28 SM 16 significant relationship between Daytime cough age and prevalence of periods of NS 4 cough and/or phlegm; EX 7 dose-response relationship SM 16 between number of cigarettes and ugh 3 mos/yr symptoms reported; data not NS 3 given EX 5 SM 14 Liard et al., 899 men and women, Men Respiratory symptoms (cough and/or 1980, aged 20-60+, NS 16.0 phlegm 3 mos/yr. for 2 years); not a France (av. 39), Paris SM 25.4 random sample; male and female Women smokers had similar symptom NS 8.1 prevalence; female nonsmokers had SM 26.5 lower prevalence 6¢ TABLE 2.—Continued Author, year, country Population Cough Phlegm Other Comments Park, 856 university Morning Morning Breathlessness on exertion Symptom prevalences apparently 1981, men and women, NS 16.0 NS 20.1 NS 23.2 not age-adjusted; significance Korea aged 18-29, EX 31.3 EX 22.9 EX 25.0 levels not reported; nonstand- Seoul SM 34.0 SM 26.1 SM 29.7 ard questions; symptoms current Daytime Daytime NS 42 NS 2.1 EX 83 EX 146 SM 109 SM 12.0 Nightime Nightime NS 13.5 NS 73 EX 18.8 EX 10.4 SM 19.9 SM 13.2 Neukirch et al., 2,266 secondary Usual cough and/or phlegm 21.8% of boys, 32.2% of girls 1982, school students, Boys were current smokers; girl France aged < 11->18 NS 26.1 smbdkers had higher symptom (mean 14.9), SM 34.9 prevalence than boys if total Paris Girls lifetime cigarettes > 4,000; results NS 26.9 probably not age adjusted SM 44.7 Schenker et al., 5,686 women, Chronic cough Chronic phlegm Wheeze most days or nights Cough and phlegm most strongly 1982, aged 17-74 (mean NS 5.6 NS 45 NS 7.2 related to current cigarettes/day: US. 44.6), western EX 75 EX 6.7 EX 8.3 tar content had independent Pennsylvania, SM SM SM effects; age effect seen for telephone interviews 1-14 91 1~14 72 1-14 14.4 nonsmokers, but not current 15-24 17.0 15-24 16.7 15-24 18.5 smokers; symptom 25+ 31.8 25+ 24.8 254 28.0 prevalences age adjusted TABLE 3.—Prevalence (percent of cough, phlegm, and other symptoms for nonsmokers (NS), smokers (SM), and ex-smokers (EX), longitudinal studies Author, year, country Population Smoking habits Symptoms Comments Ferris et al., 1,201 men and Cough Phiegm 72.3% of men, 78.4% of 1976, women, aged 25-74 1973 1967 1973 1967 1973 women followed up; 1973, US. in 1961, Berlin Men symptom prevalences, age New Hampshire NS 6.0 85 89 76 adjusted to compare with 1967, EX 20.5 9.7 23.3 159 showed little change SM 1-14 22.2 25.5 17.9 275 15-24 35.4 26.5 31.8 30.0 25-34 26.1 25.7 33.8 32.4 35+ 50.6 56.4 37.1 519 Women . NS 44 - 6.2 81 14 EX 3.2 5.2 73 10.1 SM 1-14 10.7 10.0 11.6 98 15-24 19.5 16.3 218 98 25-34 27.2 16.1 22.5 218 35+ 44.7 31.0 43.1 41.2 Kiernan et al., 2,738 men and Cough day or night in winter Effects of chest illness before age 1976, women, aged 25, born 1966 1971 1966 1971 2, father’s vocation, and current Great Britain in 1946, exams in NS NS 55 49 smoking significant; air pollution 1966 and 1971 NS SM 72 9.6° effect not significant; current SM SM 143 18.5* smoking had largest effects SM EX 9.2 5.8 * Prevalence, 1966 vs. 1972, p <0.05 TABLE 3.—Continued Author, year, country Population Smoking habits Symptoms Comments Leeder et al., 2,130 fathers, Cough/phlegm prevalence range In male ex-smokers, prevalence 1977, mean age 31.0+6.1, Men of cough/phlegm decreased Great Britain 2,148 mothers, 1st period 2nd _ period Ist 3-yr period 2nd 3-yr period over time; no significant mean age 27.9+5.3, NS NS 8.6-9.6 9.2-11.1 change in prevalence in female children born NS SM 48-16.9 13.3-20.5 ex-smokers, but numbers 1963-1965, SM SM 25.6-30.2 30.8-34.0 were small London, 6 year SM EX 21.8-25.3 §.8-20.7 followup Women NS NS 49- 68 5.8 7.3 NS SM 8.2-10.2 13.3-18.4 SM SM 16.3-22.4 23.0-28.4 SM EX 4.1-22.5 12.2-14.3 Woolf and Zamel, 302 women, aged Cough and/or phlegm Breathlessness 60% followed up; all subjects 1980, 25-54 at initial Ist exam Final exam lst exam Final exam maintained consistent smoking Canada atudy, 5-year NS 10 14 10 5 habits for 5 years followup EX 3 13 18 8 SM 56 54 25 21 69 TABLE 3.—Continued Author, year, country Population Smoking habits Symptoms Comments Beck et al., 1,262 white Usual cough Usual phlegm 55% followed up; health indices 1982, residents, aged 7-55+, 1972 1978 1972 1978 1972 1978 of respondents and non- US. Lebanon, Connect- Men respondents similar; symptom icut, exams in NS NS 5 2 7 3 prevalence tended to decline, but 1972 and 1978 NS SM 0 0 0 4 few changes were significant, SM SM 23 21 22 26 * Prevalence, 1972 vs. 1978, SM EX 25 2° 18 8 p <05 EX EX 7 6 12 15 Women NS NS 7 4 5 6 NS SM 0 0 0 9 SM SM 20 14 15 ll SM EX 28 12 8 EX EX 10 4 1 Ex-smokers urrently 1-20/day 60+ C] Never smoked Pp a 3 Currently > 20/day 45-59 Women 30-44 15-29 Age 85 + BO 4 75 70 4 65 + 60 55 50 4 45 yp 40 35+ 30 ah 25 > 20 + 1S 104 S+ QO Men 3044 15-29 Age [ 85 5 80 4 75 4 70 + 60 + rg o ° Lrg 2 e w 2 Lr > we = y ¢ “= NN N = = Percent prevalence 65 + FIGURE 11.—Prevalence of chronic cough and/or chronic sputum among samples of men and women in Tucson, Arizona SOURCE: Lebowitz and Burrows (1977). Dose-Response Relationships The most common measures of dose are the number of cigarettes currently smoked per day and the pack-years of cigarette consump- tion; the latter estimates lifetime exposure by integrating the number of cigarettes smoked (by pack) and the duration of cigarette use. Errors of memory compromise the accuracy of retrospective information, which may also be biased by differential recall in those 63 50.0 = >20 10-19 400 ~ Smokers Cigarettes/day o 1-9 Ss 300-4 5 5 € 2 200 =£ a e Ex-smokers 10.0 —4 © Nonsmokers 0.0 T | t 18-23 24-27 28-32 233 Tar (mg/cigarette) FIGURE 12.—Percentage of smokers with phlegm production (adjusted for age), according to tar yield of cigarettes SOURCE: Higenbottam et al. (1980). with and without smoking-related symptoms or diseases. Even accurate reports of current smoking habits fail to take into account all the sources of variation in exposure associated with the material used in cigarette manufacture or generated in the burning of cigarettes. The dose of noxious materials received is also influenced by human behavior, including the number, volume, and timing of puffs taken with each cigarette; retention of smoke in the mouth; depth of inhalation; disposition of the cigarette between puffs; and other aspects of smoking style that are not reproduced by the smoking-machines used to measure tar and nicotine yield. Prevalence rates of cough or phlegm, or both, generally increase as the number of cigarettes smoked per day increases. The trends illustrated in Figures 11 and 12 were present in both sexes and all age groups (Lebowitz and Burrows 1977; Dean et al. 1978; Higgins et al. 1977; Huhti et al. 1978; Higenbottam et al. 1980; Schenker et al. 1982), Bland et al. (1978) found a dose-response relationship in secondary school children, among whom rates of reporting cough were higher in those who smoked most, even though levels of cigarette consumption were generally reported to be low. At the other extreme of the age range the trend is also apparent, even though symptomatic smokers are more likely than asymptomatic smokers to stop smoking or to reduce their cigarette consumption 64 (Higgins 1974; Fletcher 1976). Symptoms were more prevalent among heavier smokers of filter cigarettes as well as of nonfilter cigarettes (Dean et al. 1971). Prevalence rates of cough, phlegm, chronic bronchitis, and mucus hypersecretion show a similar pattern of association with pack-years of exposure (Tager and Speizer 1976; Lebowitz and Burrows 1977). Rates of incidence and remission observed in longitudinal studies add further support to the strong evidence that respiratory symptoms increase as exposure to cigarette smoke increases (Table 3). In their study of more than 18,000 male civil servants in London, Higenbottam and colleagues (1980) found that the percentage of smokers who produced phlegm increased with increased daily cigarette consumption and also with increasing tar content of cigarettes among those who smoked less than 20 cigarettes a day. Symptoms were prevalent about equally among smokers of 20 or more cigarettes per day, regardless of the tar yield of the brands they used (Figure 12). Schenker et al. (1982) reported the relationship of tar content of cigarettes to respiratory symptoms in a cross-sectional telephone survey of 5,686 adult women in rural Pennsylvania. The risk of chronic cough and phlegm was more strongly affected by the number of cigarettes smoked per day than by tar content. Cough and phlegm were reported least often by never smokers and with increasing frequency as the number of cigarettes smoked per day increased. Tar content of cigarettes was significantly associated with symptoms of chronic cough and phlegm—especially cough—and its effects were independent of the number of cigarettes smoked per day in a multiple logistic analysis. The risk (relative odds) of chronic cough for smokers of high tar cigarettes (20 or more mg) was approximately twice that for smokers of an equivalent number of low tar cigarettes (10 or less mg). A limitation of this cross-sectional study was the determination of tar content for current cigarettes only, rather than for lifetime smoking habits. Although the apparent relationship between tar content and symptoms could have been caused by changes in smoking habits, this was considered unlikely because symptomatic smokers tend to reduce their consumption of cigarettes more than asymptomatic smokers (Fletcher et al. 1976) and may also switch to low yield cigarettes. In this situation, any reported effect of tar content on symptoms would be an underestimate. In summary, the prevalence of symptoms increases with dose of smoke exposure, when dose is measured by number of cigarettes smoked per day or tar content of the cigarette smoked. Relationship of Cough and Phlegm to Sex and Age Prevalence rates of cough and phlegm ascertained in epidemiologi- cal studies generally increase with age and are higher in men than 65 in women, as shown in Figure 11 and Tables 2 and 3. Rates also vary with smoking habits. Rates in nonsmokers better clarify associations of symptoms with age and sex than do rates in smokers, since they are less confounded by variations in exposure to cigarette smoke. However, recent evidence linking passive smoking with increased prevalence of respiratory symptoms suggests that rates in nonsmok- ers may be in excess of those that would be found in a population compietely free of exposure to cigarette smoke (Lefcoe et al. 1983; Weiss et al. 1983). Rates of reporting cough or phlegm or both were roughly equal in nonsmoking men and women in several cross-sectional studies (Bland et al. 1978; Higgins et al. 1977; Lebowitz and Burrows 1977; Manfreda et al. 1978; Neukirch et al. 1982; Rawbone et al. 1978). Rates were higher in nonsmoking men in some populations (Dean et al. 1977; Liard et al. 1980; Tager and Speizer 1976). Bouhuys et al. (1979) found no sex difference in the prevalence of cough, but a higher rate of reporting phlegm in male nonsmokers (Table 2). In most of these studies, the rates were not corrected for exposures to other respiratory irritants in the workplace or in the general environment. In general, symptoms are more prevalent in male smokers than in female smokers (Table 3). However, differences in prevalence rates between the sexes are generally smaller or absent when comparisons are made between men and women who smoke similar numbers of cigarettes. Lebowitz and Burrows (1977) found that the excess prevalence of symptoms in male smokers compared with female smokers tended to be greatest at older ages, where there are also the greatest differences in smoking behavior. Men in these birth cohorts tend to have begun smoking earlier in life, smoke more cigarettes per day, inhale more deeply, and smoke higher tar and nicotine or unfiltered cigarettes. Two studies from France, Burghard et al. (1979) and Neukirch et al. (1982), concentrated on high school students. In general, the prevalence of smoking was similar for both boys and girls for the two studies, although the Neukirch group found a somewhat higher rate among the girls (46 percent versus 39 percent). Slightly more boys than girls, however, smoked more than 10 cigarettes per day. In these two studies, the prevalence of symptoms was higher among female smokers than among male smokers. These data suggest that the past differences in prevalence of symptoms between the sexes is largely attributable to differences in cigarette consumption. These differences were substantial in the past, and are still present among older adults, whereas current smoking practices are about the same in male and female adoles- cents and young adults. Prevalence rates of cough, phlegm, and chronic bronchitis in- creased with increasing age in the U.S. population samples studied 66 by the National Center for Health Statistics (1981) and in several of the cross-sectional studies cited in Table 2. However, differences in rates of reporting symptoms among people of different ages may relate to effects of aging, differences in current exposures, or differences in exposure to cigarette smoke or other noxious agents in the past. It is therefore difficult or impossible to use cross-sectional data to separate effects of aging from effects of duration, dose, and nature of cigarette smoke exposure throughout life. Longitudinal studies provide information on time trends, both in exposure and in onset and course of disease. Nevertheless, conclusions may be incorrect if people who drop out of longitudinal studies are different from those who continue to participate. Prevalence of symptoms increased with increasing age among men in cross-sectional data from Tucson (Figure 11), but the trend was more apparent among smokers and ex-smokers than among non- smokers. However, Lebowitz and Burrows (1977) could not distin- guish between an association caused by increasing age and an association due to increasing duration of exposure to cigarette smoke in smokers because the two were so highly correlated. Among women, symptoms were reported more frequently at ages 30 to 44 than at ages 15 to 29 (except by ex-smokers), but prevalence rates were essentially the same for the three groups over age 30. Higgins et al. (1977) found that there was no increase in cough and phlegm with increasing age in male or female nonsmokers in Tecumseh (Michigan), whereas prevalence rates increased with increasing age in male smokers. The pattern in female smokers was similar to that in Tucson and showed an increase with age up to age 30 or 40, but rates declined with increasing age after age 50. The extent to which these patterns related to amount smoked or duration of smoking was not reported, but these older birth cohorts of women probably began to smoke later in life and smoked fewer cigarettes per day, according to national smoking survey data. In other cross-sectional studies cited in Table 2, symptom preva- lence increased with age in the populations studied (Bouhuys et al. 1979; Dean et al. 1977; Gulsvik 1979; Huhti et al. 1978; Tager and Speizer 1976), but the trend was noted by Gulsvik to be less in nonsmokers. Huhti et al. found a significant increase with age among nonsmokers for phlegm and dyspnea only. Schenker et al. (1982) observed a trend for nonsmokers but not for smokers, and Tager and Speizer found that adjusting for smoking eliminated the trend with age. Prevalence rates of cough and phlegm on two occasions 3 to 6 years apart are shown in Table 3 for five recent longitudinal studies of populations in the United States, Canada, and Great Britain. Kiernan et al. (1976), Leeder et al. (1977), Woolf and Zamel (1980), and Beck et al. (1982) found little change in the prevalence of 67 symptoms among continuing nonsmokers during the followup inter- val of up to 6 years. The rates among nonsmokers reported by Ferris et al. (1976) are similar on the two occasions, but symptoms were presented by smoking habits at followup only, and any effect of age was deliberately adjusted out because the authors’ purpose was to evaluate effects of changes in smoking, changes in pollution, and trends over time independent of changes in age. Cough and phlegm appeared to be more frequent at followup in the persistent smokers studied by Kiernan et al. (1976) and Leeder et al. (1977), and about the same in women studied by Woolf and Zamel (1980) and in men studied by Beck et al. (1982). However, rates were slightly lower at followup in the female smokers followed by Beck. Even though starting to smoke or quitting can be eliminated as the explanation for increases or decreases in symptom prevalence over the course of these studies, it is possible that changes in the number or type of cigarettes smoked by persistent smokers influenced the prevalence of symptoms. The duration of followup in all these studies was relatively brief, and it is still difficult to distinguish between effects of aging and effects of duration, amount, and nature of exposure to cigarette smoke in smokers, even when major changes in smoking behavior are controlled. However, available data suggest that age itself is not the major factor responsible for differences in the frequency or distribution of symptoms in populations of nonsmokers and smokers. Relationship of Cough and Phlegm to Airflow Obstruction Many cross-sectional studies have found associations between cough, phlegm, chronic bronchitis, or mucus hypersecretion and reduced levels of pulmonary function. The forced expiratory volume at 1 second (FEV) has been measured in most clinical studies and in nearly all epidemiological studies, and mean levels of FEV: are generally slightly lower in groups of people who report respiratory symptoms (USPHS 1964, 1971; USDHEW 1979; USDHHS 1980a, 1981). Recent studies have compared other measures of pulmonary function in people with and without symptoms and have provided longitudinal data on pulmonary function for symptomatic and asymptomatic smokers and nonsmokers. Attention has been given to understanding the natural history of chronic airways obstruction and the interrelationships of respiratory symptoms, levels and rates of decline of pulmonary function, and their independent and interrelated associations with cigarette smoking. Several investiga- tors have emphasized the desirability of identifying in advance those smokers who will develop severe COLD; symptoms and other characteristics have been evaluated as potential predictors of morbidity or mortality from COLD. 68 Fletcher and colleagues ( 1976) found that the age—height standard- ized FEV at the initial survey of their population of working men in London was inversely related to the volume of sputum produced in the first hour after getting up. The regression of FEV; on age, given height, was steeper for symptomatic cigarette smokers than for asymptomatic smokers or nonsmokers. However, the authors cau- tion that men may develop symptoms as they age and change from one regression slope to the other. Burrows et al. (1977a) found that an index of cough or sputum was related to FEV: percent predicted when pack-years of smoking were controlled in a multiple regression analysis. Regressions of FEV, percent predicted on pack-years are shown for people with and without chronic cough and sputum in Figure 13; the intercept at 0 pack-years was lower and the decline in FEV; with increasing pack- years was significantly greater for those with chronic cough and sputum than for those with no cough or sputum. The authors calculated that values of FEV: were lower by about 10 percent in people with cough and sputum, regardless of smoking habits, and that values declined by about 4 percent of predicted for each 10 pack- years of smoking in people with cough and sputum and by about 2 percent in subjects without productive cough. There was a signifi- cant relationship between FEV; and pack-years of smoking in asymptomatic smokers in this population. A weaker relationship between cough and sputum and Vmax was also found to be independent of pack-years of smoking; however, prediction equations for flow rates have been revised substantially (Knudsen 1983), and the extent to which relationships between the revised flow rates and pack-years of smoking differ in symptomatic and asymptomatic subjects has not been reported. Dosman et al. (1976) found poor correlations between respiratory symptoms and dynamic lung compliance, closing volume, closing capacity, slope of phase III, and helium flow-volume curves in a study of 49 smokers and 60 nonsmokers who were recruited from a smoking cessation clinic, a personnel department, and the staff of a laboratory. In their community-based studies of children and adults, Bouhuys and colleagues (1977) studied relationships between respiratory symptoms and loss of lung function in smokers and nonsmokers. They found that residual values (observed-predicted) of FVC, FEV), PEF, MEF ‘sox, and MEF 2% were not significantly different in people with no symptoms or only one symptom when analyses were done separately for adult white male smokers and nonsmokers. When a Symptom score was used to combine information on usual cough, usual phlegm, wheeze, and dyspnea, decrements in lung function were greatest among those with most symptoms. 69 No cough or A sputum (n= 1,492) Total population without chronic cough and chronic sputum (n = 1,803) Percent FEV, 80 =4 70 4 Subjects with chronic cough and chronic 5 sputum (n = 247) 0 v T T T 20 40 60 80 Pack-years Figure 13.—Percentage distribution of predicted forced expiratory volume in 1 second (FEV:) versus pack-year of cigarettes smoked, by cough and sputum history SOURCE: Burrows et al. (1977a). In a study (Detels et al. 1982) designed to assess the relative sensitivity and specificity of symptoms, the flow-volume curve (FV), the single breath nitrogen test (SBNT), and specific airway conduc- tance (Scaw) for identifying COLD were compared with the FEVi/FVC ratio and with one another in 1,201 residents of Los Angeles 25 to 29 years old. The tests were done in 1978-1979 at a followup examination of a previously defined cohort. Prevalence rates of cough and sputum were 9 percent in never smokers, 26 70 percent in current smokers, and 33 percent in smokers of 20 or more cigarettes a day. Prevalence rates of an abnormal FEV:/FVC ratio in these groups were 8, 23, and 33 percent, respectively (the FEV:/FVC ratio was considered abnormal if it was below the 95th percentile for never smokers without a history of respiratory illness). The research- ers found that there was very little overlap between the presence of productive cough and abnormal tests, and that none of the tests of function showed reasonable concordance with this symptom. Lack of reasonable concordance meant that none of the other tests were abnormal in 50 percent or more of the individuals with productive cough. In this study, the FEV:/FVC ratio was used as the standard against which the sensitivities of the other tests were judged; the sensitivity of the FEV:/FVC itself was evaluated by its agreement with those tests found to be sensitive in the study. The lack of an independent method for identifying COLD, the cross-sectional na- ture of these data, and the way in which analyses were done restrict the ability to make biological inferences about the independence of the effects of cigarette smoking that lead to cough and sputum or to chronic airflow limitation. However, the authors note their findings are consistent with the hypothesis that effects of smoking on cough and sputum are independent of effects on airflow limitation. Insights into the course and pathogenesis of COLD have been developed by Fletcher and his colleagues from observations made during their 8-year longitudinal studies of levels and rates of decline in lung function in middle-aged working men in London (Fletcher 1976; Fletcher et al. 1976). These investigators found that various measures of sputum production were correlated with FEV: standard- ized for height and age, and that this correlation was weakened only slightly by adjusting for smoking habits. The researchers maintained that the association between sputum production and pulmonary function could be due entirely to a common causation. Some men with mucus hypersecretion had normal FEV;; conversely, some men with airflow obstruction did not report phlegm. Nevertheless, the relationship between phlegm and reduced FEV: was strong enough to give rise to an estimated reduction in FEV) of about 0.1 liters for every ml of sputum expectorated in the first hour after getting up. However, because decline in FEV; (FEV: slope) was not related to measures of sputum production when level of FEV; and smoking habits were controlled, the researchers concluded that mucus hypersecretion is not a cause of accelerated decline in FEV}. Furthermore, there was no evidence that short-term changes in sputum production were associated with short-term changes in FEV:. The researchers concluded that the association between expectoration and reduced FEV; is caused by the increased suscepti- bility of some people to both expectoration and excessive loss of FEV; when they are exposed to cigarette smoke or, presumably, to 71 other noxious materials. This study has made important contribu- tions to understanding the natural history of chronic bronchitis and emphysema, but the duration of followup was only 8 years, the men were 30 to 59 years of age at the start of the study, and their mean age was 51 years at the midpoint. Similar studies of younger men and women and observations over longer periods of time are needed to extend these findings. Johnston et al. (1976) found that sputum volume was not related to decline in FEV: in a 10-year followup study of chronic bronchitic patients. There was no difference in sputum volume between patients whose FEV: fell by more than 33 percent and controls (matched on initial FEV: ) whose FEV: did not fall. Furthermore, sputum volume was reduced in response to stopping smoking or to antibiotic treatment, whereas rate of decline of FEV: was unaffected. In this and other studies (Higgins et al. 1970; Fletcher et al. 1976; Peto et al. 1983) FEV: was strongly predictive of morbidity and mortality, whereas respiratory symptoms were not. Woolf and Zamel (1980) studied “normal” employed women aged 25 to 54 in a longitudinal study designed to identify smokers at increased risk of developing COLD. Ventilatory function was mea- sured at the beginning and at the end of a 5-year period during which smoking habits and symptoms were ascertained annually. Differences between initial and followup values of pulmonary function tests were expressed as a percentage of the initial value and compared in persistent nonsmokers and persistent smokers who either consistently reported or consistently denied cough or sputum. The decline in FEV:, FEVi/FVC, and FEF275% was greater in symptomatic smokers than in asymptomatic nonsmokers, but not significantly different in asymptomatic smokers compared with either nonsmokers or symptomatic smokers. The average number of cigarettes smoked during the course of the study was greater for smokers with cough and sputum. Change in FEF25-75% was evaluated in individual smokers, and no association was detected between cough and sputum and percentage change in this measure of lung function. The investigators identified one group of smokers whose decline in FEF2s-75%, was similar to that in nonsmoking women and another group with a greater decline; cigarette consumption was similar in the two groups. The investigators concluded that individu- al susceptibility is an important determinant of the effect of cigarette smoking, because some women develop symptoms and others remain symptomless but experience rapid worsening of ventilatory function. However, they noted a tendency for both cough and sputum and rapid worsening of ventilatory function to coexist. The number of women in some groups was very small, and the measure of decline in lung function used by these researchers does not take into account regression to the mean or assess absolute 72 reduction; those with smaller initial values will have greater percentage reductions for a constant absolute reduction in function. Followup studies at 10 and 15 years of the Tecumseh, Michigan, population showed that incidence rates of obstructive airways disease were higher in men and women who reported cough, phlegm, or both symptoms (chronic bronchitis) at entry compared with those who denied these symptoms (Figure 14) (Higgins et al. 1982). Both cough and chronic bronchitis were significant predictors of obstruc- tive airways disease in men even when smoking habits were controlled in multiple logistic analyses. However, respiratory symp- toms were poorer predictors of impaired pulmonary function at followup than were smoking habits and baseline levels of lung function. In a multiple logistic model with age, smoking habits, and level of lung function as risk factors, over 60 percent of the 10-year incidence cases developed among men and women in the top 10 percent of the risk distribution, whereas only 36 percent of incidence cases were in the top decile of risk when cough, rather than FEV, was used as a risk factor (Higgins 1984). Summary Cigarette smoking is associated with respiratory symptoms, in- cluding mucus hypersecretion, and with prevalence and incidence of COLD manifested by irreversibly impaired pulmonary function. While some smokers develop both conditions, and those with cough and phlegm are at increased risk of developing airways obstruction, the conditions can occur separately by mechanisms that are imper- fectly understood but appear to be different. The excess risk of reduced FEV: or COLD in symptomatic smokers compared with asymptomatic smokers may be a reflection of increased susceptibili- ty in some individuals. However, it may also be a measure of increased dose of cigarette smoke, in that smokers who report cough and phlegm tend to smoke more heavily than smokers who deny these symptoms, and measures such as numbers of cigarettes smoked per day are not precise enough to control adequately for the amount of smoke exposure. The rate, number, and volume of puffing as well as the depth of inhalation can vary substantially between smokers and are important additional measures of cigarette smoke exposure dose. 73 4380-144 0 - 85 - 4 a“ g Q Cc re S Oo ~ 2 5 z £ 8 g 6 a t y —€ ¢« ANY i ge 2 c= Coa a = —_—_——_— [ « oO 8 —_— 4. + io OQ uw ° 2 £ Q ¢c e a KX Cc ° £ Oo Phiegm Men Cough 18 107 54 0 incidence of obstructive airways disease (percent) FIGURE 14.—Age-adjusted 15-year incidence of obstructive airways disease, by cough, phlegm, and chronic bronchitis status at entry to the study, Tecumseh, ages 16 to 64, 1962-1979 SOURCE: Higgins et al. (1982) 74 CHRONIC AIRFLOW OBSTRUCTION Introduction Airflow obstruction is the physiological consequence of disease processes that narrow the airway. In asthma the obstruction is reversible with pharmacologic bronchodilation, whereas the obstruc- tion associated with airways damage and emphysema is often not reversible. The terminology with regard to permanent airflow obstruction has varied. The 1958 Ciba Foundation Guest Symposium proposed “generalized obstructive Jung disease,” which was subdivid- ed into “asthma” and “irreversible or persistent obstructive lung disease” (1959); in the 1962 recommendations of the American Thoracic Society, “chronic obstructive bronchitis” was the only definition that mentioned abnormality of expiratory flow (American Thoracic Society 1962). In 1975, a joint committee of the American College of Chest Physicians and the American Thoracic Society recommended the term “chronic obstructive pulmonary disease” ‘American College of Chest Physicians and American Thoracic Society 1975). Thurlbeck (1976, 1977) has advocated the use of “chronic airflow obstruction,” a functionally based definition that does not specify the underlying disease processes. Previous Reports of the Surgeon General have used varying terminology, including “chronic bronchopulmonary disease” in 1964, “chronic obstructive bronchopulmonary disease” in 1971, and “chronic obstructive lung disease” in 1979 (USPHS 1964, 1971; USDHEW 1979). These definitions, however, cannot be readily applied to identify specific populations. Physiologists, epidemiologists, and clinicians often use differing approaches in determining whether airflow obstruction is present (Fletcher 1978). Physiologists, with the capability for making sophisticated laboratory measurements of airflow obstruction, may regard subtle early abnormalities of flow as definitive. In the community, epidemiologists have generally used spirometry as the primary method for assessing airflow obstruction. For epidemiologic purposes, airflow obstruction is usually defined by a forced expiratory volume in 1 second (FEV)) less than a particular level after standardization for sex, age, and height, or by a ratio of the FEV: to the forced vital capacity (FVC) below a specified value. Tests of forced exhalation, such as the FEV 1, have the advantage of sensitivity to abnormalities of both the lung parenchyma and the airways (Mead 1979). Clinicians are more likely to detect and diagnose airflow obstruction when it is advanced and symptomatic. As would be anticipated, the differing approaches of physiologists, epidemiologists, and clinicians may lead to differing estimates of the frequency of airflow obstruction. The natural history of chronic airflow obstruction in adults has been partially described by several recent prospective investigations: n ‘ or