of emphysema found in patients with COLD to be present to a significant degree in nonsmokers. Thurlbeck (1963) reported 19 patients who had severe emphysema at autopsy. All 19 were cigarette smokers, in contrast to 18 smokers out of 38 patients who did not have significant emphysema at autopsy. Anderson et al. (1964) conducted a more systematic evaluation of the relationship between cigarette smoking and the degree of emphysema at autopsy. They found that 12 of 23 patients without emphysema were cigarette smokers, whereas 55 of 84 with mild emphysema, 30 of 33 with moderate emphysema, and 14 of 15 with severe emphysema were cigarette smokers. Petty et al. (1967) reported similar findings, with 6 of 57 patients with moderate emphysema at autopsy being nonsmokers and only 1 of 61 patients with severe emphysema being a nonsmoker. Ryder et al. (1971) found that of 21 patients whose lungs showed more than 25 percent emphysema, only 1 was a nonsmoker. Thurlbeck et al. (1974) examined the relationship of age to extent of emphysema in smokers compared with nonsmokers in the combined autopsy populations of the teaching hospitals in three separate cities. The severity of emphysema was quantified using a panel grading method, with a score under 25 representing mild emphysema. They found that the degree of emphysema increased slightly in nonsmokers beginning in the fifth decade and reached an average score of 10 to 15 in men and 4 to 6 in women by the eighth and ninth decades. In contrast, male smokers had an average score of 25 to 30 by the seventh decade and maintained this level for the next two decades. Sutinen et al. (1978) (Table 13) examined the relationship between prevalence and extent of emphysema and duration of the smoking habit. As would be expected from previous studies, moderate or severe emphysematous changes were limited to smokers. However, these changes were also limited to those smokers who had smoked for 20 or more years, and severe emphysema was reported only in those who had smoked for 40 years or more. These data, coupled with that of Thurlbeck et al. (1974) describing only mild emphysematous changes in nonsmokers with advancing age, suggest that emphyse- ma is a late pathologic change in cigarette-induced lung disease. This correlates well with the clinical experience of severe emphysema being rare prior to the fifth decade. It also suggests that cessation, even among middle-aged smokers, may have substantial impact on emphysema morbidity and mortality. Dose-Response Relationships Some studies have reported the extent of emphysematous change in smokers of different numbers of cigarettes per day. Spain et al. (1973) examined the lungs of 134 subjects who died suddenly and 126 TABLE lb-Correlation between the severity of emphysema at autopsy and total smoking duration Prevalence of emphysema (percent1 by total smoking years Grade of emphysema 0 1-19 2cL39 40 or more Total Ko emphysema Mild (grades 5 to 201 Moderate (grades 30 to 50) severe (grade 60 or morel 61.6 81.6 21.2 0.8 43.1 38.4 15.4 69.7 50.0 45.8 9.1 26.5 7.6 14.7 3.3 All grades 36.4 15.4 788 91.8 56.9 Total number 73 I3 33 34 I53 NOTE: P c O.C0@5; X2 test. wth groups of moderate and 8evere emphysema and of smoking times I-19 and 2% 39 years combtned SOURCE Sutmen et al 119781 who had no previous history of lung disease. They found emphysema- tous changes greater than grade 20 (mild emphysema) in 10 percent of nonsmokers, 36 percent of smokers of less than one pack per day, and 39 percent of smokers of more than one pack. A much larger study was conducted by Auerbach et al. (1972, 19741, who examined whole lung sections from 1,443 men and 388 women autopsied between 1963 and 1970. Table 14 describes the relationship of age, smoking habits, and degree of emphysema graded on a scale of 0 to 9, with 9 representing severe emphysema. It is clear that severe emphysema is limited to smokers, and that the severity of emphysematous change at autopsy increases with in- creasing number of cigarettes smoked per day during life. This study also found that almost all (94.5 percent) smokers of more than one pack per day had some degree of emphysema (slight, moderate, advanced, or far advanced) (Table 15). In contrast, 93.8 percent of nonsmokers had either none or minimal emphysema. This evidence would suggest that emphysematous change is a nearly universal phenomenon in heavy smokers, but is rare in nonsmokers, and that it is the large ventilatory reserve of the lungs that restricts clinically manifest disease to those individuals with far advanced emphysema. Similar results were reported in a more limited number of autopsies done on female smokers (Auerbach et al. 1974) (Table 16). A study of microscopic lung sections from the autopsies of 1,436 men and 388 women was also reported by Auerbach et al. (19741, and closely paralleled the results of the whole lung study. However, they also reported the results in smokers who had quit for more than or less than 10 years prior to death (Table 17). The degree of emphysematous change was still related to the amount smoked, but 127 TABLE 14.-Degree of emphysema in current smokers= and in nonsmokers, according to age groups `; 60 Cui-rent cigarette smoked ~ ':t I7 1: 1 "t 2+ i ,x7 k 2 11 12 4 2 5 5.5 31 0 10 004 3s 0 83 0 13 17 2 40 :30 0 39 0 13 I% 4 4 0 95 0 16 - til x2 0 YI 166 0 39 I) 11 23 1.29 0 26 4 1 4 2 1 12 190 0.X 2 10 13 5 1 31 2 15 0 17 3 9 17 12 4 - 4.5 2.37 0.16 5 9 3 1 1 19 3.59 0.35 8 23 10 7 2 1 51 2.98 WXI 2 24 130 50 P 4 3 - Z?l 2.56 2.86 0 07 0.10 4 37 42 11 x 5 - 107 3.39 0 15 2 40 38 11 9 12 - 112 368 0 1: 62 3 37 020 - 44 3.91 0.n SOURCE Auerbach et al ll972' was less in those who had quit for more than 10 years prior to death, suggesting that the cessation of smoking results in a slowing of the 128 TABLE 15.-Age-standardized percentage distribution of male subjects in each of four smoking categories, according to degree of emphysema Degree of emphysema M) 75 (none) l-1.75 (mmimaii 2-2.75 (sIghtI 33 75 Imoderate) t9 00 (advan& to far adsanwl `Packages da> SOURCE. Auerbach et al (1972) TABLE 16.-Means of the numerical values given lung sections at autopsy of female current smokers, standardized for age SubJects who never smoked regularly Current cigarette smoken Number of subjects Emphysema Fibrosis Thickening of arterioles Thickening of arteries 252 0.05 0.37 0.06 001 10 years stopped l Pack l Pack 66 51 131 0.70 1.08 1.69 1.74 2.44 3.30 0.93 1.25 1.59 0.16 0.36 0.61 NOTE: Numeneal values for each finding were determined by rating each lung section on scales of S4 for emphysema and thrckenmg of the arterioles, CL7 for librosis, and C-3 for thickenmg of the arteries. SOURCE Auerbach et al (1974) proteinase inhibitory activity and the demonstration of the frequent early development of emphysema in such subjects (Ore11 and Mazodier 1972) called attention to the critical step of fibrous tissue proteolysis in the remodeling of lung structure. It also pointed to at least one potential explanation for the variability in extent of emphysema among smokers. Together with data from animal experiments, the discovery of the PiZZ defect and its association with emphysema has led to general acceptance of a theory of imbalance between the extracellular levels of proteinase and proteinase inhibitor in the lung as the cause of panacinar emphysema in subjects with this deficiency. The patho- genetic lessons learned from a,-proteinase-inhibitor deficiency also afford plausible explanations for other forms of emphysema, espe- cially emphysema associated with cigarette smoking. Homozygous Deficien t-Pi22 In his classic description of the severe (PiZZ) deficiency of the aI- proteinase inhibitor, Eriksson (1965) did not indicate an effect of cigarette smoking on the development of emphysema. Later studies, however, did recognize smoking as a potential aggravating factor (Kueppers and Black 1974; Larsson 1978) and reported that PiZZ persons who smoked cigarettes were destined to experience shortness of breath 10 to 15 years earlier (Figure 27) and to die sooner than PiZZ persons who did not smoke (Figure 28). 130 I Men I Smokers Nonsmokers T women Smokers . 81. . . i 11. . . . . . . . . . T . . . . . Nonsmokers . . . . . . . i 0 o FIGURE 27.-Age at onset of dyspnea in 169 PiZZ individuals separated according to sex and smoking history NOTE The hormntal lines show the me&an values. The difference between nonsmokers and smokers was highly s~gnrficant for both sexes and was 13 and 15 years for men and women. respezt~vely SOURCE: Larsson /1978, More recent studies, however, have shown considerable variation in the rate of decline of lung function among middle-aged PiZZ adults (Buist et al. 19831. In a comparison of 22 persons with PiZZ phenotype who had never smoked with 36 PiZZ smokers, Black and Kueppers (1978) found variability in symptoms and lung function abnormalities in both groups. Smokers generally sought medical attention earlier, and those who reached the older age groups, such as 60 to 69, had smoked less and started to smoke later in life. There was overlap in these characteristics between the age groups, however, and some smokers did live into the 50 to 69 age range. In this analysis, the correlations between pulmonary function test abnormalities and pack-years of cigarette smoking were small. The British Thoracic Society, in a multicentered study of PiZZ individuals (Tobin et al. 19831, reported an association between 131 0 Nonsmokmg PiZ men and women A All Swedish women All Swedish men 20 30 40 60 60 70 60 90 100 Age (IIT yeam) FIGURE 28.-The cumulative probability of survival, given that 20 years of age is reached, in smoking and nonsmoking Swedish PiZZ individuals, compared with all Swedish men and women NUI'E Surv~al was tugher for PlZZ nonsmokers than for PiZZ smokers in both exe8 above age 35 SOURCE. Lamson (19781 cigarette smoking and the onset of pulmonary symptoms and deterioration of lung function, but demonstrated no significant correlation between the quantity of tobacco consumed and the extent of pulmonary dysfunction. A notable finding in this study, applicable to other studies of the natural history of disease related to a1- proteinase-inhibitor deficiency, was the impressive difference be- tween individuals found because of medical complaints (index cases) and those detected by surveys (nonindex cases). Nonindex cases had better pulmonary function and survived longer than index cases, irrespective of other variables such as age and smoking history. The distinction between these two categories of subjects suggests the importance of factors besides the PiZZ phenotype in the development of symptomatic lung disease in PiZZ persons. PiZZ individuals who smoke increase their risk for early onset of symptomatic chronic obstructive lung disease and for a shortened lifespan, compared with nonsmoking PiZZ individuals. However, pulmonary function data have shown only limited differences in diffusing capacity and elastic recoil between the smokers and the nonsmokers (Black and Kueppers 1978). 132 He terozygous De ficien t-Pi117 The PiMZ phenotype of a,-antiproteinase inhibitor occurs in approximately 3 percent of the population. Because of the high frequency of emphysema in PiZZ persons, it is important to establish whether PiMZ individuals also have an increased risk of emphysema and chronic obstructive lung disease. From the unpredictability of obstructive lung disease even among those with the PiZZ phenotype, however, one might expect difficulty in discerning the effect of the PiMZ phenotype. Among adults with symptomatic chronic obstructive lung disease, the PiMZ phenotype is more prevalent than expected (Mittman 1978). It is uncertain whether this means of subject identification is appropriate, as was noted concerning index and nonindex PiZZ individuals. Madison et al. (1981) emphasized the complexity of this issue by noting that the PiMZ phenotype was only one of several factors that appeared to be related to the risk of obstructive lung disease. Other factors identified as relevant included smoking, a family history of lung diseases, and being male. From studies of children and young adults it is evident that the PiMZ phenotype does not strongly predispose to chronic pulmonary disease. Thus, PiMZ children (Buist et al. 1980) failed to show any early changes of lung dysfunction analogous to what has been observed in some young PiZZ individuals; PiMZ adults below the age of 40 had the same results by spirometry and the single breath N2 test as PiMM individuals matched for smoking history (Buist et al. 1979b). Numerous studies involving older subjects indicate that PiMZ individuals preserve their lung function, as measured by spirometry, compared with controls matched for smoking (Tattersall et al. 1979, de Hamel and Carrel1 1981). The elastic properties of the lungs may be different in PiMZ persons, but if there are differences, they are small. Larsson et al. (1977) reported that 50-yearold PiMZ men who smoked had reduced elastic recoil at total lung capacity compared with PiMZ nonsmokers, even though they had no evidence of impaired air flow. The PiMZ nonsmokers were indistinguishable from PiMM nonsmokers. Tattersall et al. (1979) also found no effect upon airflow in PiMZ middle-aged men, and a statistically nonsignif- icant decrease in elastic recoil. Using an index of the slope of the pressur+volume curve, Knudson and Kaltenborn (1981) found no significant reduction in elastic recoil of PiMZ subjects compared with matched PiM controls. There is little direct information about the occurrence of emphyse- ma among PiMZ individuals. In an autopsy study, Eriksson et al. (1975) found emphysema among 13 of 26 subjects with diastase- resistant PASpositive inclusions in the liver, compared with an incidence of emphysema of only 18 percent in the controls. Although 133 these findings suggest an increased occurrence of emphysema with the PiMZ phenotype, this study should be interpreted cautiously because the smoking histories of the subjects and the quantification of the emphysema were not included. Moreover, the significance of the PAS-positive inclusions is not certain, because one recent study found that such inclusions represented immunoreactive al-protein- ase inhibitor in only half of the tissue studied (Qizilbash and Young- Pong 1983). It may be concluded from the studies involving a,-proteinase- inhibitor-deficient people that for those with the PiMZ phenotype, smoking has not been shown to promote a greater risk of emphysema than it does in PiMM persons. In the rare individual with PiZZ, the risk of emphysema is extremely high in both smokers and nonsmok- ers, but PiZZ smokers experience an earlier onset and more severe chronic obstructive lung disease than PiZZ nonsmokers. Observations in Experimental Animals Experimental animals have been subjected to cigarette smoke to examine whether changes typical of emphysema result. As noted below, it appears that cigarette smoke exposure can produce emphysematous-like changes in the lungs under experimental conditions, but the exposure must be quite prolonged and intense, or additional factors must be employed to "sensitize" the lungs to the effects of cigarette smoke. Pioneering studies in dogs exposed to cigarette smoke, by Hernan- dez et al. (1966) and by Auerbach et al. (19671, indicated effects consistent with emphysema, but these reports did not include quantitative morphology or data about the mechanical properties of the lungs. Moreoever, the exposures may have created problems of hypoxemia and infection that may have influenced the responses to cigarette smoke. Contrary to these findings, in later studies, beagles that inhaled cigarettes by face mask in four sessions per day for up to 1 year-an inhalation sufficient to raise the blood carboxyhemoglo- bin saturation to 5.4 + 0.9 percent-had no statistically significant changes in mean linear intercept or internal surface area, although their large airways showed epithelial cell hyperplasia, proliferation of goblet cells, and peribronchial inflammation (Park et al. 1977). Recently, Hoidal and Niewoehner (1983) presented data suggesting that cigarette smoke may be an important cofactor in the develop ment of elastase-induced emphysema. They found that inhalation of cigarette smoke led to severe emphysema in hamsters if used in conjunction with doses of elastase that did not produce emphysema when used alone. In this study, hamsters were exposed to cigarette smoke for 15 minute periods, six times per day, 6 days per week for 7 weeks in standardized chambers. The animals were challenged with small doses of elastase given intratracheally; controls consisted of 134 animals given either elastase or smoke exposure or neither. Animals receiving only smoke or only elastase showed no changes of mean linear intercept or volume-pressure relationship of the excised lungs, compared with animals given neither elastase nor smoke exposure. The combinations of smoking followed by elastase or smoking both before and after elastase produced statistically signifi- cant increases of mean linear intercept, displacement upward and to the left of the volume-pressure curves (Figure 29), and marked emphysema by light microscopy of inflation-fixed lungs. The mecha- nism of the synergism between elastase and smoking was not elucidated. One possibility considered was that cigarette smoke impaired the repair mechanism normally triggered by elastase exposure, a possibility supported by Osman et al. (19821, who found that hamsters exposed to cigarette smoke after intratracheal elas- tase did not show the heightened lung elastin synthesis typically seen after lung injury produced by elastase. summary Clinically significant degrees of emphysematous lung destruction are commonly present in individuals with COLD. Severe emphysema occurs almost exclusively in cigarette smokers and those with homozygous a,-antitrypsin deficiency. The extent of emphysematous change increases with increasing numbers of cigarettes smoked per day and with the duration of the smoking habit. While clinically significant emphysema is limited to a minority of those who smoke, most heavy smokers have some degree of emphysematous change by the sixth decade of life. Individuals with homozygous a,-antitrypsin deficiency have an exceptionally high risk of developing emphysema. This risk is present for both smokers and nonsmokers, but smokers with a,- antiprotease deficiency develop clinical symptoms earlier in life. It is unclear whether individuals with heterozygous antiprotease pheno- types are at increased risk of developing COLD. Summary and Conclusions 1. Cigarette smoking is the major cause of COLD morbidity in the United States; 80 to 90 percent of COLD in the United States is attributable to cigarette smoking. 2. In population-based studies in the United States, cigarette smoking behavior is often the only significant predictor for the development of COLD. Other factors improve the predictive equation only slightly, even in those populations where they have been found to exert a statistically significant effect. 3. In spite of over 30 years of intensive investigation, only cigarette smoking and a,-antiprotease deficiency (a rare genet- 135 o NO smoke, no elastase ? ~ontmuous smoke, no elastase * No smoke, elastase 0 Posf-elastase smoke A Pre-elastase smoke A ~ontmuous smoke. elastase p. ,05 compared wlh * No smoke. no elastase I I I I I I 5 10 15 20 25 30 Pressure (cmHtO) FIGURE 29.-The effects of combining cigarette smoking and elastase upon the pressure-volume characteristics of the lungs of experimental animals N(rTE. The m vttro measurements of lung volume are shown as percentage of predicted total lung capacity cTLCr relative to transpulmonary pressure of hamster lungs following m vwo exposure to venous combmatlons of agarette smoke and mtratracheally admlnlstered pancreatic elastase Values are the mean t SEM of messurement~ made dunng deflation Tbe animals that smoked and then recewed elastase tPre-Elastase Smoke) and those that smoked both kfore and after elastase lContmous Smoke. E1asta.wI had slgmficant changes m the elastx properties of the lungs There were no changes from control if elastase or smoking were used separately or when smoking occurred onI?. after elastase SOURCE Holdal and N,ewcehner / 19831 ic defect) are established causes of clinically significant COLD in the absence of other agents. 4. Within a few years after beginning to smoke, smokers experi- ence a higher prevalence of abnormal function in the small airways than nonsmokers. The prevalence of abnormal small airways function increases with age and the duration of the 136 smoking habit, and is greater in heavy smokers than in light smokers. These abnormalities in function reflect inflammatory changes in the small airways and often reverse with the cessation of smoking. 5. Both male and female smokers develop abnormalities in the small airways, but the data are not sufficient to define possible sex-related differences in this response. It seems likely, how- ever, that the contribution of sex differences is small when age and smoking exposure are taken into account. 6. There is, as yet, inadequate information to allow a firm conclusion to be drawn about the predictive value of the tests of small airways function in identifying the susceptible smoker who will progress to clinical airflow obstruction. 7, Smokers of both sexes have a higher prevalence of cough and phlegm production than nonsmokers. This prevalence in- creases with an increasing number of cigarettes smoked per day and decreases with the cessation of smoking. 8. Differences between smokers and nonsmokers in measures of expiratory airflow are demonstrable by young adulthood and increase with number of cigarettes smoked per day. 9. The rate of decline in measures of expiratory airflow with increasing age is steeper for smokers than for nonsmokers; it is also steeper for heavy smokers than for light smokers. After the cessation of smoking, the rate of decline of lung function with increasing age appears to slow to approximately that seen in nonsmokers of the same age. Only a minority of smokers will develop clinically significant COLD, and this group will have demonstrated a more extensive decline in lung function than the average smoker. The data are not yet available to determine whether a rapid decline in lung function early in life defines the subgroup of smokers who are susceptible to developing COLD. 10. Clinically significant degrees of emphysema occur almost exclusively in cigarette smokers or individuals with genetic homozygous al-antiprotease deficiency. The severity of em- physema among smokers increases with the number of ciga- rettes smoked per day and the duration of the smoking habit. 137 Appendix Tables Ar.YYY a. --I'u v 1 IN wn~te adults, by smoking status, sex, and age, United States, 1971-1975 Both eexea Men Women Cigarette smoking etatua by age) N n Mean SD SE N " Mean SD SE N n Mean SD SE Never smokers L&74 3140' 21' 3669' 39' 2664' 191 25-34 6733 394 3607 791 51 2633 130 44.04 xi4 63 4099 264 3095 312 26 3.544 5278 291 3171 607 49 1669 61 3742 591 73 3609 210 2907 397 40 4.544 4642 353284a 594 35 1206 85 3487 626 72 3736 268 2631 401 29 55-64 3660 251 2511 589 31 &lo 59 3215 531 61 2781 192 2289 401 29 65-74 2875 235 2148 549 36 461 43 2856 627 96 2394 192 2oG6 402 36 Exsmokers 25-14 3112 24 3623 37 2651 28 25-34 2811 160 3677 810 60 1359 66 4303 627 92 1452 94 3091 441 55 35-44 3oF% 171 3566 767 69 1828 94 4013 643 70 1256 77 2916 361 44 45-54 3323 213 3155 742 65 2345 143 3414 663 69 978 70 2535 454 65 55-64 2669 181 2845 693 63 1826 130 3067 649 63 843 51 2319 456 90 6&7.! 1769 157 2366 6% 66 1270 121 2533 699 78 491) 36 2020 487 92 Smokers 25-74 2378 20 3281 32 2514 n ,I 2fAu 6665 487 3567 752 44 4792 239 4037 639 51 4093 248 3018 433 41 34-Mb 5849 320 3166 655 47 3027 156 3507 639 71 '2822 162 2800 439 43 4554 5606 374 2761 623 37 n43 182 3126 579 49 2863 192 2411 437 40 55-64 3251 192 2416 631 50 1700 106 2736 632 63 1551 84 2w4 m 50 65-74 933 84 2071 653 66 534 56 2222 556 79 400 28 1669 714 155 g TABLE A.--Continued Both eexea Men Women Qarette smoking ___ status (by age) N n Mean SD SE N n Mean SD SE N " Mean SD SE Light smokers 2s74 2534 3&44 454 55-64 65-74 Moderate smoker8 25-74 25-34 35-44 4.544 55-64 65-74 Heavy smokers 25-74 ?A-34 35-44 45-54 5544 &74 2951 38 3311 3425 650 97 879 43 3914 3106 618 93 308 17 37751 2683 490 73 383 24 3009 24@3 573 83 313 18 2919' 2150 737 165 131 11 222P 508 515 404 660 426 57 102 139 95 150 130 1283 70 a59 55 707 52 730 39 172 10 2626 52 3m WY 88 2891 479 83 2507 437 76 2190 350 62 2095' 901 3% 25 51 47 51 70 124 38 80 64 92 121 150 2162 113 1267 72 1090 76 1043 57 304 21 2678 23 3335 3671 810 60 2534 123 4136 3217 646 68 1214 66 3593 2679 634 53 1145 75 3106 2406 589 63 690 45 2776 2023 609 105 261 28 22.79 40 69 99 79 60 126 2466 2991 393 2836 395 2368 429 1977 408 1693' 4.84 684 624 622 455 572 1735 112 1199 64 1570 104 597 37 203 16 4269 235 2413 130 2715 179 1287 82 464 44 2785 32 3202 3514 699 70 1363 72 3927 3143 684 71 1505 75 3382 2930 649 70 1193 62 3164 2440 741 118 697 45 2619 2038' 606 151 130 16 2096' 52 82 89 75 133 172 2409 2979 393 2562 373 2411 440 lF&' 396 17&Y* 215 2417 136 2148 116 1779 118 922 53 154 18 597 646 579 737 638 1051 64 643 41 586 36 224 8 24 2 NOTE: N = weighted population estimate in thousands; n = number of people in sample; SD = standard deviatmn. SE = standard error. I Adjusted by the direct method to reflect the age distribution of the U.S. populatmn at the midpoint of the survey. ' Doe8 not meet ntanti of reliability. SOURtX National Center for Health Statiirca. Unpublished data fmm the first National Health Nutrition and Examination Survey (NHANFS 1). TABLE B.-Flow at 25 percent of FVC for white adults, by smoking status, sex, and age, United states, 1971-1975 Both sex.88 Men Women Cigarette smoking - statue by age) N n Mean SD SE N n Mean SD SE N " Mean SD SE Never smokers 25-74 2544 35-44 4554 5.544 65-74 Exsmokers w74 2534 3b4.4 4.544 5544 6s74 Smokers 25-74 2534 35-44 4554 55-64 65-74 6733 394 5278 291 4942 353 3660 251 2675 235 2811 160 3086 171 3323 213 2669 181 1769 157 487 320 374 192 84 6253' 6639 6377 5742 5368 46% 6093 6835 7020 6270 5763 4918 5647 6760 6157 5471 5123 3954 1591 1464 1566 1397 1576 1855 `2041 1896 1764 1946 1694 1740 1658 1815 1566 47' 7261' 98 2633 130 7871 114 1669 81 7715 90 1206 85 7262 101 880 59 6543 102 481 43 6097 62 7095 203 1359 66 6042 176 1828 94 7956 164 2345 143 6765 144 1826 130 6261 WI 1270 121 5194 47 6362 102 4792 239 7606 123 3027 158 6848 92 2743 182 6130 132 1700 108 5567 181 534 56 4199 1513 1545 1796 1593 1951 1715 !2059 1919 1820 2091 1663 1675 1763 2061 1745 91' 5343' 36' 157 4099 264 5847 1042 89 176 3609 210 5758 952 80 213 3736 268 5252 1141 70 265 2781 192 4996 1091 83 298 2394 192 4331 1303 108 107 5188 67 285 1452 94 5705 1126 165 232 1258 77 5659 965 116 185 978 70 5Q34 1176 151 160 I343 51 4749 1058 197 265 499 36 4213 1278 197 88 5002 52 126 4093 248 5769 1061 83 160 2822 162 5415 1200 102 137 2863 192 4840 1233 106 223 1551 84 4636 1372 169 238 400 28 3627 1274 255 c 4 TABLE B.--Continued L.. Both sexm Men Women Cigarette smokmg - data8 (by age) N n Mean SD SE N " Mean SD SE N n Mean SD SE Light smokers 2574 2.534 3544 45-54 !i5-64 65-74 Moderate smokers a-74 25-34 3.5-M 45-54 55-64 G-74 Heavy smokers 2.5-74 75-34 3!i44 4544 5.544 6574 2162 113 1267 72 1090 76 1043 57 304 21 4269 2413 2715 1287 464 2417 2146 1779 922 154 23.5 130 179 82 44 136 116 118 53 18 5834 6549 KM 5545 5222 3779 5661 6909 6384 5269 5065 3950 5485 6691 5964 5712 5090 415!'2 1652 1461 1476 1534 1272 1719 1786 1490 1787 1717 1659 1815 1940 2117 1653 91 6569 209 879 43 1688 211 308 17 7250' 217 383 24 6373 238 313 18 6096' 345 131 11 37421 66 6430 136 2534 123 7647 194 1214 66 7348 111 1145 75 5821 202 690 45 5576 304 261 28 4356 85 6219 l&i 1363 72 7468 198 1506 75 6363 207 1193 82 6326 321 697 45 5322 401 130 16 4180' 1690 1634 1572 1616 1279 1667 1736 1661 1897 1692 1640 1902 1920 2288 1758 142 5171 293 1283 70 5769 369 959 55 5653 311 707 52 5096 399 730 39 4849 462 172 10 3807' 118 164 1735 112 236 1199 64 183 1570 104 334 597 37 404 203 16 151 225 1054 64 261 643 41 251 586 36 434 224 8 463 24 2 4967 5831 5408 4867 4475 3427' 4822 5685 5031 4458 437P2 4023 2 1071 1193 1203 1333 1266 1120 1212 1202 1439 1285 1018 1084 1257 1202 904 112 140 188 193 249 489 76 132 170 137 265 319 111 176 18f 26f 3.x 62! NOTE: N = Weighted population estimate. in thousanda; n = number of people in sample; SD = standard deviation; SE = standard error. ' Adjusted by the direct method to reflect the age distribution of the U.S. population at the midpoint of the survey. ' Doea not meet Btandards of reliability ~UWE National Center for Health Statistics. Unpublished data from the first Natmnal Health Nutrition and Examination Survey (NHANES 1). TABLE C.-Flow at 50 percent of J?VC for white adults, by smoking status, sex, and age, United states, 1971-1975 Both eexee Men Women Cigarette smoking status (by age) N " Mean SD SE N " Mean SD SE N " Mean SD SE Never smokers 25-74 25-34 3544 4544 55-64 65-74 3743 ' 38' 40831 6733 394 4361 1194 69 2633 130 4998 5278 291 3904 1164 84 1669 81 4315 4942 353 3366 1212 84 1206 85 3972 3660 251 3090 1087 74 880 59 3736 2875 235 2535 1045 73 461 43 3157 86' 128 152 150 l&l 174 3342' 3964 3713 3170 2886 2410 34' 78 91 90 72 84 1255 1221 1287 1220 1060 4099 264 3609 210 3736 x33 2781 192 2.394 192 963 989 1119 955 996 Ex-smokers 25-74 25-34 35-44 45-54 s-64 65-74 Smokers 25-74 25-34 3!i-44 45-54 55-64 65-74 3579 59 4188 67 3123 81 2811 160 4329 1292 120 1359 66 5029 1243 3086 171 4249 1364 129 18'28 94 4702 1410 332.3 213 3474 1404 114 2345 143 3749 1426 2669 181 3110 1411 118 1826 130 3294 1362 1769 157 2524 1296 121 1270 121 2578 1364 195 1452 94 3674 949 114 180 1258 77 3590 1037 160 143 978 70 2816 1091 147 127 843 51 nil 1432 293 153 499 36 2384 1092 167 3475 4546 3764 3257 2193 1889 59 103 140 92 146 175 z 3325 2604 2361 1965 54 90 98 94 144 252 3169 39 4126 1268 74 3552 1296 87 2924 1208 76 2567 1248 107 1922 1220 159 s&35 487 5849 320 5606 374 3251 192 933 84 4792 239 3027 158 2743 182 1700 108 534 56 1296 1399 1278 1364 1174 4093 248 2822 162 2863 192 1551 84 400 28 1037 1137 1040 1062 1279 ;: TABLE C.-Continued Both eexen Men Women Cigarette smoking -___- status by age) N n Mean SD SE N n Mean SD SE N n Mean SD SE Light smokers 25-74 2534 35-44 4544 5s64 t&74 Mcderate smokera &I4 25-34 35-44 45-a !s-& 65-74 Heavy smokers 25-74 25-34 3544 45-54 55-64 66-74 102 2162 113 1230 1248 994 162 1267 72 1076 943 1054 166 1090 76 864 969 771 103 1043 57 1375 1643 1080 200 304 21 1252 883 1415 425 3313 3964 3630 2911 2756 2056 74 169 879 43 151 308 17 107 383 24 205 313 18 292 131 11 3676 4617 4190' 3150 3542' 1706' 110 222 1263 70 226 959 55 197 707 52 395 730 39 366 172 10 2984 3516 3450 2781 2420 2321' 57 71 4269 235 1239 96 2534 123 1297 872 47 2413 130 1182 124 1214 66 1198 llcfl 142 2715 179 1205 111 1145 75 1243 1125 140 1287 82 1186 167 690 45 1191 1134 245 464 44 1239 218 261 28 1316 1047 266 3207 4246 3781 n75 2665 1881 3561 4640 4039 3079 2873 2131 79 126 1735 112 171 1199 64 124 1570 104 207 597 37 n9 203 16 2888 3671 3520 2553 2425 1558' 68 110 2417 136 1333 153 1363 72 1306 1295 247 2148 116 1469 166 1505 75 1103 185 1779 118 1355 147 1193 82 1377 1062 222 922 53 1123 173 697 45 1222 651 232 154 18 1113 285 130 16 1059 703 490 3043 4067 3239 3152 2284 1760' 3287 4326 3456 3458 2379 1559' 92 197 1054 64 m 64.3 41 168 5% 36 221 224 8 274 24 2 2828 3733 n3i 2526 1997' 28.34' NOTE N = weight& population eetunata. in thousanda; n = number of people io sample; SD = ntandard deviation; SE = standard error. ' Adjusted by the direct method to reflect the age distribution of the U.S. population st the midpoint of the .wrvey. * Doea not meet standards of reliiiity. SOURCF.. National Center for Health Statistics. Unpublished data from the funt National Health Nutrition and Examination Survey (NHANFS 1). TABLE D.-Flow at 75 percent of FVC for white adults, by smoking status, sex, and age, United states, 1971-197s Both eexe8 Men Women Cigarette smokii &ha (by age) N II Mean SD SE N n Mean SD SE N n MWII SD SE Never smokers 25-74 1230' 28' 1329' 42' 1073 ' 24' 25-34 6733 394 1776 714 52 Xi33 130 2065 649 72 4099 264 1690 691 62 36-44 5278 291 1277 621 49 1669 81 1478 8.43 129 3609 210 1184 456 32 `a-54 4942 353 1044 636 44 1206 85 1184 664 14 3736 268 999 620 53 55-64 3660 251 737 611 36 880 59 978 612 83 2781 192 661 449 34 65-74 2675 235 609 463 32 481 43 795 4x3 64 2394 192 572 465 38 Exsmokers 25-74 1152 29 1403 41 992 37 25-34 2811 160 1696 678 61 1359 66 1925 664 109 1452 94 1480 616 72 354 3086 171 1460 664 62 1828 94 1623 693 92 1258 77 1224 538 59 45-54 3323 213 10% 625 48 2346 143 1148 666 59 978 70 734 376 53 5544 2669 181 734 541 54 1826 130 178 446 41 843 51 638 694 156 65-74 1769 157 588 506 43 1270 121 592 516 47 499 36 578 481 87 Smokers 2574 967 22 1053 29 889 34 25-34 8885 487 1530 688 41 4792 239 1665 665 60 4093 248 1373 692 65 3M.4 5849 320 1062 552 34 3027 158 1134 599 57 2822 162 985 4% 35 45-54 5606 374 778 511 31 2743 182 866 530 41 2x63 192 693 478 43 c5.564 3251 192 631 536 42 1700 108 713 580 63 1551 84 541 468 56 6.5-14 933 84 452 689 loo 534 56 350 445 17 400 28 558 901 199 r ts TABLE D.-Continued Both @exe8 Men Women Cigarette smoking - statue (by age) N n Mean SD SE N n Mean SD SE N n Mean SD SE Light smokers 25-74 25-34 35-44 45-54 55-64 65-74 Moderate smokers 25-74 25-34 35-44 4x4 55-64 65-74 Heavy smokers 25-74 25-34 35-44 45-54 55-6-t 65-74 2162 113 1261 72 1090 76 1043 57 304 21 4269 235 2413 130 2715 179 1281 82 464 44 2417 136 2146 116 1719 118 922 53 154 18 1049 1460 1122 837 706 660 970 1603 1134 711 643 373 882 1447 940 836 529 297' 679 534 4.31 540 1040 685 499 480 598 366 689 595 589 410 453 44 94 879 43 63 309 17 57 383 24 85 313 18 264 131 11 28 57 2534 123 52 1214 66 49 1145 15 12 690 45 68 261 ?a 47 956 95 1363 72 1503 63 1505 15 995 57 1193 82 941 57 697 45 545 112 130 16 258' 1120 1641 1294' 840 931' 393' 1107 1755 1265 801 784 381 587 686 517 416 637 375 593 647 416 64 985 113 1283 IO 1366 101 959 55 1067 131 707 52 836 182 730 39 609 231 172 10 864' 41 846 82 1735 112 1362 78 1199 64 lOCKI 41 1570 104 656 119 597 37 481 85 203 16 363' 38 815 101 1054 64 1374 85 643 41 811 73 586 36 620 62 224 8 479' 98 24 2 505' 703 531 388 450 1244 620 443 514 503 353 790 422 438 388 603 67 127 73 42 88 414 32 76 58 67 69 103 82 172 69 79 160 420 NOTJC N = weighted population estimate, in thousands; n = number of people in sample; SD = standard deviation; SE = standard error. ' Adjusted by the direct method to reflect the age distribution of the U.S. population at the midpoint of the survey. `Does not meet standards of reliability. SoUfKT National Center for Health Statisticsa. Unpublished data from the first National Health Nutrition and Examination Survey (NHANFS 1). TABLE E.-FEVI/FVC ratio for white adults, by smoking status, sex, and age, United States, 1971-1975 Both sexes Men Women Cigarette smoking etatua Car age) N " Mean SD SE N n Mean SD SE N n Mean SD SE Never smokers 25-74 25-34 3.544 45-54 55-64 65-74 Ersmokem 25-74 25-34 35-u 45-54 55-64 65-14 Smokers 25-74 25-34 35-M 45-54 55-64 674 79.1' 0.21' 82.5 6.06 0.34 60.3 5.67 0.37 78.7 5.84 0.38 11.6 5.03 0.35 76.5 6.41 0.52 11.9 ' 0.34 ' 80.1 5.91 0.69 18.8 5.25 0.64 71.5 5.95 0.17 15.8 5.13 0.81 13.5 7.59 1.14 80.2 ' 0.23 ' 83.6 5.93 0.44 80.9 5.73 0.45 79.0 5.75 0.41 78.2 4.85 0.39 71.0 5.97 0.55 18.1 0.41 82.4 5.81 0.18 80.4 5.26 0.69 77.0 5.04 0.69 76.0 6.60 1.36 15.3 6.58 1.05 17 5 0.39 81.1 6.85 0.61 78.2 6 16 0.41 15.4 6.32 0.52 16.0 6.61 0.15 73.6 8.67 2.09 6733 394 5278 291 4942 353 3660 251 2875 235 24233 130 1669 81 1206 85 880 59 481 43 4039 264 3609 210 3736 268 2781 192 2394 152 77.1 0.30 81.7 5.92 0.53 79.5 6.26 0.56 76.2 6.58 0.50 73.7 7.79 0.70 11.5 9.34 1.05 76.6 0.44 80.9 5.94 0.94 78.8 6.78 0.83 75.9 1.10 0.66 12.1 8.07 0.19 10.0 9.83 120 2811 160 3086 171 3323 213 2669 181 1169 157 1359 66 1828 94 2345 143 1826 130 1270 121 1452 94 1258 77 918 10 843 51 499 36 75.9 0.26 80.3 6.78 0.38 76.7 7.28 0.46 74.2 7.05 0.41 73.1 8.13 0.59 69.8 9.40 1.44 14.0 036 19.2 6.50 0.52 75.3 1.92 071 13.0 1.55 059 10.6 9.59 1.03 67.0 8.94 1.54 8885 5849 5606 3251 933 487 320 374 192 84 4792 3027 2743 1700 534 239 4093 248 2822 162 2863 192 1551 84 400 28 156 182 108 56 z TABLE E.-Continued al Both wxea Men Women Cigarette smoking statue (by age) N n Mean SD SE N n Mean SD SE N n Mean SD SE Light smokers 25-74 25-34 36-44 45-S 55-64 65-74 Moderate smoker8 25-74 25-34 3544 45.54 55-64 65-74 Heavy smokers 25-74 2x34 3544 45-54 5564 65-74 2162 1267 1090 1043 304 424% 2413 2715 1287 464 2417 2148 1779 922 154 77.3 0.47 113 80.9 7.43 0.84 72 78.4 6.18 0.79 76 76.5 4.94 0.66 57 76.9 7.06 0.97 21 71.4 10.59 2.65 75.8 0.36 235 80.4 6.36 0.53 130 77.9 6.18 0.65 179 73.6 7.48 0.69 82 73.2 7.46 0.81 44 69.3 8.30 1.46 75.1 0.58 136 79.1 6.65 0.73 116 14.2 8.24 0.92 118 73.7 7.21 0.74 53 68.9 10.08 1.42 18 68.0' 9.18 2.66 879 308 383 313 131 2534 1214 1145 690 %I 15.7 43 80.3 11 17.1' 24 75.1 18 74.8' 11 64.6' 74.6 123 19.3 66 77.3 75 71.3 45 72.1 28 68.4 72.8 72 78.0 75 73.3 82 74.0 45 67.1 16 66.9' 7.10 6.14 6.05 9.cQ IO.84 6.29 6.61 7.87 8.00 7.63 6.33 8.68 7.34 10.09 8.75 0.76 1.11 1.54 1.58 2.25 4.17 0.48 0.70 0.85 0.96 1.38 1.56 0.57 0.89 1.21 0.86 1.81 2.42 1283 959 107 730 172 1735 1199 1054 643 586 224 24 78.7 0.60 70 81.4 7.62 1.30 55 78.8 6.13 1.30 52 77.3 4.01 0.54 39 77.8 5.81 0.87 IO 76.5' 6.90 2.64 76.9 0.47 112 81.9 6.16 0.13 64 18.6 5.64 0.71 104 75.3 6.67 0.80 37 14.3 6.58 1.07 16 70.4' 893 2.42 77.2 1.06 64 81.9 6.90 1.16 41 76.2 6.64 1.15 36 73.2 6.91 1.30 8 74.6' 7.63 2.40 2 79.4' 6.66 4.63 NtX'Ez N = weighted population estimate. in thousands; n = number of people in sample; SD = standard deviation; SE = standard error. `Adjusted by the direa method to reflect the age distribution of the U.S. population at the midpoit of the survey. ' Lhm not meet .stan&rds of reli.tbility. SOURCE Natuxsd Center for Health St&tics. Unpublished data from the fii Natiaxal Health Nutrition and Examination Survey WGNES 1). TABLE F.-MMEF for white adults, by smoking status, sex, and age, United States, 1971-1975 Both wxw Men Women cigarette 8mokiLtg atah (by age) N " Mean SD SE N " Mean SD SE N n Mean SD SE Never emokera 2s74 25-34 35-44 4564 5M4 65-74 Exsmokers 25-74 2.5-34 35-44 4554 5544 65-14 Smokem 25-74 25-34 35-M 4.554 55-64 65-14 3020' 3748 3140 2724 2301 1891 29' 64 58 50 43 51 3392' 4357 3501 3198 2734 2314 52' 106 106 113 104 130 2664' 3357 2973 2512 2164 1806 26' 58 58 48 51 56 51 103 104 102 180 115 41 77 63 66 18 220 1023 821 837 6733 394 5278 291 4942 353 3660 251 2815 236 2633 130 1669 81 1206 85 880 59 481 43 lCJJ3 911 1021 163 827 4199 3609 3736 n81 234 264 210 268 192 192 820 in 703 663 611 730 619 2910 3753 3500 2800 2318 1826 41 102 106 91 75 82 3324 4321 3882 3021 2463 1865 66 162 157 114 81 99 2537 3222 2944 2270 2005 1128 1066 1165 1111 948 873 2811 160 3086 171 3323 213 2669 181 1769 157 1359 66 1828 94 2345 143 18% 130 u-70 121 1014 1237 1171 953 922 1452 54 1258 77 978 70 843 51 499 36 809 165 714 857 123 2553 3512 2850 2283 1955 1474 31 66 65 54 67 118 2786 3857 3033 2511 49 93 107 18 106 104 2343 3109 2654 2065 1813 l&i5 4792 3027 2743 4093 248 2822 162 2863 192 1551 84 403 28 872 8lm 109 654 995 8835 5849 5636 3251 933 437 320 374 192 84 1069 970 8-96 854 831 239 158 182 109 56 1101 1073 1007 1700 534 985 677 TABLE F.--Continued Both eerxa Men Women cigarette smoking 8tatf.M (by age) N n Mean SD SE N n Mean SD SE N n Mean SD SE Light smokers 25-74 25-34 35-44 45-54 55-64 65-74 Moderate smokers 2b-74 25-34 3544 45-64 5E-64 65-14 Heavy smokers 25-14 25-34 35-44 4544 55-64 65-74 2162 113 1267 72 1090 76 1043 57 304 21 424% 235 2413 130 2715 179 1287 82 464 44 2417 136 2146 116 1779 118 922 53 154 18 2736 3457 2936 2334 2252 1667 2542 3605 2993 2169 1894 1395 2404 3389 26243 2421 1706 1313' 1034 839 641 894 102-3 1106 907 82.3 811 738 1018 1663 1087 764 591 57 2985 144 819 43 3923 110 308 17 3`uma 84 383 24 2521 124 313 18 2694' 257 131 11 1339' 41 2848 93 2534 123 3S60 99 1214 66 3257 14 1145 75 2245 103 690 45 2144 12.6 261 28 1535 53 2620 120 1363 72 3614 119 1505 75 n77 125 1193 82 2663 166 697 45 1754 151 130 16 12471 1044 760 806 1239 563 1132 968 891 848 746 1045 1144 1145 828 601 93 2510 196 1283 70 3137 184 959 55 2787 173 707 52 2232 321 730 39 2063 238 172 10 1917' 64 2266 123 1735 112 3087 145 1199 64 2725 92 1570 104 2041 162 597 87 1604 159 203 16 1214* 72 2210 167 1054 64 3122 157 643 41 2280 150 536 36 1926 136 224 8 1557' 160 24 2 1665' 807 808 502 605 1206 828 752 744 655 687 911 135 766 439 369 17 153 124 68 87 404 40 98 92 95 106 157 87 187 123 185 169 NOTI? N = weighted population estimate. in thouann&; n = number of people in sample; SD = standard deviation: SE = standard ermr. ' Adjuted by the direct method to reflect theage distribution of the U.S. population at the midpoint of thesurvey. *Does not meet standa& of reliability. SOURCE: Natmnal Center for Health Statistics. Unpublished data from the first National Health Nutrition and Examination Survey (NHANlB 1).