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The Respiratory Effects of Regular Cigarette Smoking in Women
The Respiratory Effects of Regular Cigarette Smoking in Women* A Five-Year Prospective
Study
Colin R. Woolf. M.D.• F.C.C.P., and Noe Zamel. M.D.• F.C.C.P. Over a ftve-year period a consistent habit of smoking or nonsmoking was maintained by 302 women (aged 25 to 54 years at the beginning of the stndy). There were 130 nonsmokers, 40 u-smokers, and 15 light, 46 moderate, and 71 heavy smokers. Smokers without serious disabmty who had stopped smoking had a very low prevalence of respiratory symptoms and showed worsening of pulmonary function over the years similar to Hfe-long nonsmokers. Although there Is a dose-related response to cigarettes, individual susceptibDity also plays an impor·
A previous retrospective study of 500 women showed an increase in respiratory symptoms with an increase in the number of cigarettes smoked. Pulmonary ventilatory function, as well as diffusing capacity during exercise, showed lower results in smokers than in nonsmokers. 1•2 The results of a retrospective study of this type may not be accurate because the memory of the number of cigarettes smoked beyond five years is unreliable. 8 Of the original group, 302 women maintained a consistent habit of smoking or nonsmoking and were seen regularly over a five-year period. The purpose of this prospective study was to examine changes in clinical findings and in pulmonary function over a five-year period during which the number of cigarettes smoked had been accurately recorded. The present investigation provides a range for change in ventilatory function over a five-year period in apparently healthy nonsmoking women. Using this range, it is possible to identify susceptible smokers who show a deterioration in ventilatory function that is more rapid than normal. This type of susceptibility is not directly related to either the presence of respiratory symptoms or the number of cigarettes smoked. We found that smokers without serious disability who stopped smoking behaved like lifelong nonsmokers. We suggest that repeated spiromebic studies might be used to identify the susceptible smokers at an early stage. °From the Tri-hospital Respiratory Service and the Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Supported in part by a grant from the American Medical Association Education and Research Foundation. Manuscript received June 27; revision accepted December 10. Reprint requests: Dr. Woolf, CW.2-.200 College Wing, Toronto General H081Jital. Toronto, OntariO, Canada MSG
1L7
CHEST, 78: 5, NOVEMBER, 1980
tant role in determining the respiratory dect of smoking. A range for change in ventilatory function over a ftveyear period in apparently healthy nonsmoking women Is provided. Using this range, it Is polllble to identify susceptible smokers who show deterioration in ventllatory function that is more rapid than normal Repeated splrometric studies may be useful In selecting a group at greatest risk of developing later disabling- chronic obstructive pulmonary disease.
MATERIALS AND METHODS
The women for this study were volunteers who came mainly from large commercial firms, and all subjects considered themselves normal; that is, even if they had symptoms, they were not of a severity to require medical care. Only women between the ages of 25 and 54 years were accepted into the initial year of the study. At the time when this study commenced (over ten years ago), it was not appreciated that even younger female smokers might show signi6cant abnormalities of pulmonary function. Older women were not included because of concem that by the time that a further five years had passed, there might be an increasing number of complicating medical abnormalities. The women who took part in the prospective study were all examined initially as part of a retrospective study which has been fully described.1,2 The women were divided into five groups according to their average smoking habit over the five years of observation. Nonsmokers were those who had never smoked cigarettes. Ex-smokers had not smoked for at least one year before entrance into the study and remained nonsmokers. Light smokers were those who smoked 70 or fewer cigarettes per week, moderate smokers smoked 71 to 140 cigarettes per week, and heavy smokers smoked more than 140 cigarettes per week. There were 130 nonsmokers, 40 ex-smokers, and 15 light, 46 moderate, and 71 heavy smokers. The average age, duration of smoking on entrance into the study, and the average number of pack-years are shown in Table 1. Using analysis of variance, there was no significant difference in the mean ages of the groups. Only women who remained nonsmokers or remained smokers over the five years were included. Also, the smokers were excluded if they changed their year-by-year smoking by more than one group; for example, light smokers might become moderate smokers, but they would be excluded if they became heavy smokers. Similarly, a heavy smoker might become a moderate smoker, but if she became a light smoker, then she would be excluded. In fact, the smokers maintained a remarkable constancy for the weekly number of cigarettes smoked. The ex-smokers were only included if they had not smoked for at least one year before entering the study, and therefore the exsmokers had not smoked for at least six years by the end of
RESPIRATORY EFFECTS OF REGULAR CIGARETTE SMOKING IN WOMEN 707
Table I-Mean A••• Duration o/ Smoldq, anti Paclc·'Y-ra on Enlranee inlO S1r&d7* Group
No.
Age, yr
40.2±0.7
40
41.3±1.2
15.0±1.4
11.5±1.4
Smokers Light .. 15 Moderatet 46 Heavyi 71
43.2±1.7 39.1 ±1.1 38.6±0.9
16.7±1.6 18.0±1.0 17.5±0.9
5.2±0.8 15.0±0.9 23.7±1.4
Total
ConsisConsistently tently Absent Present
Duration of Smoking, yr Pack-Years
Nonsmokers 130 Ex-smokers
Table 2-Cluinse in S7mpeoma ONr FiH 'Yeara•
0
0
302
*Mean± SE. **Seventy cigarettes or less per week. tSeventy-one to 140 cigarettes per week. iMore than 140 cigarettes per week. the investigation. All of the women were seen once per year by the same specially trained public health nurse, and a special questionnaire was completed, with particular emphasis on an accurate history of smoking and the presence or absence of respiratory symptoms. At the end of &ve years, a full clinical examination and tests of pulmonary function were performed, as on the initial visit. The tests of pulmonary function were selected to give information about the abnormalities likely to result from smoking. These tests had shown important differences between smokers and nonsmokers in the previous retrospective studies.1,2 The tests were selected also on the basis of causing the least discomfort, in order to maintain the volunteer group over five years. Forced vital capacity ( FVC), forced expiratory volume in one second ( FEV1 ), and the mean forced expiratory flow during the middle half of the FVC (FEF25-751; formerly maximal midexpiratory flow rate) were calcu1ated from the best of at least three singlebreath tracings recorded using a water-sealed spirometer (Stead-Wells). A treadmill exercise test was performed at 1.5 mph at a 4 percent grade. Measurements for calculation of steady-state pulmonary diffusing capacity for carl>on monoxide ( Dss) were made during the fifth minute of exercise.• After the exercise test, the back pressure from carbon monoxide was measured by a rebreathing method, and an appropriate correction was made in the calculation of Dss.G The women had not smoked for at least two hours before the beginning of the tests of pulmonary function. The same tests using the same equipment were done initially and at the end of five years. To examine differences among the various groups, an analysis of variance was performed, and further comparisons were made using multiple t-tests.
Developed
Lost
Cough or sputum (or both) Nonsmokers 105 (81) Ex-smokers 34 (85) Smokers 37 (28)
7 (5) 0 50 (38)
12 (9) 5 (13) 21 (16)
6 (5) 1 (3) 24 (18)
Dyspnea•• Nonsmokers Ex-smokers Smokers
114 (88) 30 (75) 81 (61)
4 (3) 0 11 (8)
3 (2) 3 (8) 17 (13)
9 (7) 7 (18) 23 (17)
Wheeze Nonsmokers Ex-smokers Smokers
114 (88) 36 (90) 58 (44)
4 (3) 2 (5)
5 (4) 2 (5) 14 (11)
7 (5) 0 24 (18)
36 (27)
*Table values are numbers of subjects; numbers within parentheses are percents of group. **Grade 2 or 3 of Fletcher.•
Smokers frequently had symptoms, and those without symptoms initially, developed symptoms much more frequently than nonsmokers; however, it is of interest that 18 percent of the smokers lost symptoms during the five years, and this loss of symptoms occurred even though the number of cigarettes and the brand smoked during the five years remained constant. In no individual was there a change from nonfiltered to filtered cigarettes. Changes in pulmonary function after the five years of the study were related to the measurements at the initial visit. The result of a test on entering the study was subtracted from the result of that test at the end of five years, and the difference was expressed as a percentage of the initial value. As a first step, nonsmokers were compared with smokers. The FEF.25-75S (mean + SE) showed a greater decrease over five years in smokers ( -19.5 Table 3--Mean CU...e in Pulmonary' Function Ollf!Jr FiH 'Yean, Esprened aa Perce~e o/ lnitial J'alue* Group
FEV1••
FEVi/ FVCt
FEF
DBS
25-753*
(Exercise)
Nonsmokers -1.5±0.6 -6.4±0.5 -14.0±1.4 -5.9±2.8 Ex-smokers
The changes in symptoms over five years, comparing the initial and final visits, are shown in Table 2. Throughout the five years, most women remained either consistently without symptoms or with symptoms unchanged. Nonsmokers and ex-smokers initially had few symptoms, but some women developed symptoms, and in a few instances where symptoms were initially present, the women became symptomless by the time of the final examination. 708 WOOLF, ZAllEL
-0.8±0.8 -6.9±0.7 -15.0±2.2 -1.4±5.0
Smokers Light -0.4±1.7 -4.0±2.0 -18.8±5.2 -0.3±10.8 Moderate -3.0±1.9 -8.8±1.7 -17.4±2.0 -2.8±4.6 Heavy -4.6±0.8 -9.2±0.8 -21.0±2.1 -0.8±3.4 *Table values are mean percent changes ± SE. ••p <0.05 for heavy vs ex-smokers, for heavy vs light smokers, and for heavy vs nonsmokers. tP <0.05 for heavy VB nonsmokers, for heavy VB light smokers, and for moderate VB light smokers. iP <0.01 for heavy VB nonsmokers.
CHEST, 78: 5, NOVEMBER, 1980
Table 4--Mean C"--e in Pulmonary Function ONr
Fin Year•, Espreued a• Percenlqe o/ lnidal J"alue•
Smokers Cough or Sputum or Both
Data
Nonsmokers (No Cough or Sputum)
No Cough or Sputum
No. of subjects
105
37
50
FEV1
-1.1 ±0.7**
-1.7±0.9
-5.0±1.0••
FEV1/FVC
-6.2±0.6t
-6.8±0.8
-9.6±1.lt
FEF25-75%
-13.2±1.6t
-17.3±2.2
-23.9±2.5t
-6.8±3.0
-0.7±6.0
Dss
0.3±4.0
*Table values are mean percent changes ± SE. ..P<0.01. tP<0.05. tP<0.01.
±1.4 percent) than in nonsmokers ( -14.0 ± 1.4 percent; P < 0.01), and similarly the ratio of FEV1/ FVC showed a greater change in smokers ( - 8.5 ± 0.8 percent) than in nonsmokers ( -6.4 ± 0.5 percent P < 0.05). Comparisons were made between nonsmokers, exsmokers, and the smokers divided into smoking groups (Table 3). Between non-smokers and exsmokers, there were no significant differences in the results of any of the ventilatory tests over five years. The FEV1 showed a greater decrease for heavy smokers than for ex-smokers, light smokers, and nonsmokers (P < 0.05). The FEV1/FVC showed a greater fall in heavy smokers, compared with nonsmokers and light smokers; the moderate smokers showed a greater decrease in FEV1/FVC than the light smokers ( P < 0.05). The FEF25-75% showed a greater fall in heavy smokers than in nonsmokers (P < 0.01). The nonsmokers who remained without cough or sputum throughout the five years were compared with smokers, who were divided into groups depending upon the presence or absence of cough or sputum (Table 4). The FEV1, FEV1/FVC, and FEF25-75% all showed a greater fall over five years in smokers with consistent cough and sputum than in nonsmokers without these symptoms. Smokers without cough or sputum were not significantly different from either the nonsmokers or the smokers with cough or sputum (or both). The smokers without cough or sputum smoked, on the average, 31,668 ± 15,184 cigarettes (±SD) over the five-year period of observation. This was significantly less ( P < 0.01) than the average smoked by those with cough or sputum, namely, 41,236 + 12,584 cigarettes. Changes in Dss on exercise showed no significant differences over five years between nonsmokers, exsmokers and smokers, regardless of whether one
CHEST, 78: 5, NOVEMBER, 1980
divided smokers according to amount smoked or the presence or absence of symptoms (Tables 3 and 4). The mean change for nonsmokers was greater than for smokers; however, there was greater variability in the results in the smokers (note the high standard error of the mean), and comparisons of the means poorly represented the populations being considered. Changes in pulmonary function after five years in individual women were examined in relationship to age, presence of cough and sputum, and actual number of cigarettes smoked over five years. Pulmonary function changes at different rates, depending on age. As a standard, the results of linear regression analysis in nonsmokers are shown in Table 5. Older women changed more rapidly over the five years than the younger women. The percentage of change in FEF25-75% in all individual smokers and ex-smokers over five years as related to age on entering the study is shown in Figure 1. All ex-smokers fall within the normal range. Using a one-tailed distribution of the 95 percent confidence limit (dotted line in Fig 1 ) ,11 smokers ( 8 percent) fall below the limits of nonsmokers. The characteristics of this group are shown in Table 6. Ten of these women were over 40 years of age on entering the project (that is, 15 percent of the 67 smokers who were over 40 years of age). Most were moderate or heavy smokers with usually normal initial results on tests of pulmonary function. Symptoms of cough or sputum were variable. Similarly, the percentage of change in FEV1 and FEVi/FVC in all individual smokers and ex-smokers over five years as related to age on entering the study was analyzed. As for FEF25-75%, all ex-smokers fell within the range of nonsmokers. Using these tests, it was possible to identify, in addition to the 11 smokers with an abnormal change in FEF25-75%, a further seven smokers with a normal change in FEF25-75% but an abnormal change in FEV1, and Table 5--B.egreuion Equalioq /or Change in Pulmonary Function ( y) Ofler Fi11e Year• Related to Age (x) on Entering Study in NoR8n&olcer•
Test FEV1, ml Percent change
p SE of Regression Equation Estimate Value• y- -0.20:i:+6.42
160.1 6.18
<0.05 <0.01
FEVi/FVC, percent y- -0.19x+l.93 Percent change Y""' -0.23:i:+2.75
4.82 5.62
<0.01 <0.01
0.50 15.07
<0.01 <0.01
Y""' -4.4:i: +134.5
FEF25-75%, y= -0.014x+0.088 L/sec Percent change Y""' -o.oox+9.99 *Significance of slope from zero.
RESPIRATORY EFFECTS OF REGULAR CIGARmE SMOKING IN WOMEN 709
+40
• 0
+20 II.I
"cz %
•SMOKERS o EX-SMOKERS
•
•
•
•
•
0
•
8
u ~
-20
IL
2 2
-40
'~!>:
. :.
-··-·-·--•----- . •
•
•
-60 -80
•
•·Ji{·..
!a.·
0
~;-
•
•
• +-~~
......~~---~~---~~..-~
20
25
30
......~~--~~--
35
40
AGE• YEARS
!50
45
( Initial vesit)
Fromm 1. For all smokers and ex-smokers, change in FEF21S-75S (or maximal midexpiratory flow rate [MMF]) over five years (as percentage of initial value) related to age on entrance to study. Normal range is shown by one-tailed distribution of 95 percent confidence limit for nonsmokers (shaded area between aolid and broksn line&).
two others with only an abnormal change in FEV1/ FVC. The characteristics of these women are shown in Table 6 and are similar to those in the women identified by an abnormal change in FEF25-75%; however, five of the women with a normal change in FEF25-75% but an abnormal change in FEV1 were between the ages of 30 and 40 years. When all smokers were considered, 20 ( 15 percent) had an abnormal change in FEF25-75% or FEV1 or FEV1/ FVC over the five years of the study. In smokers the change in FEF25-75% as related to the presence or absence of consistent cough and sputum is shown in Table 7. Chi-square analysis shows no significant diflerence ( P > 0.1) between the number of women in whom cough and sputum were both absent or constantly present, regardless of the percentage of change in FEF25-75% over five years; however, from Table 7, one may also examine the relationship between symptoms and change in FEF25-75% in individual women. Table 7 shows that some women, in spite of consistent cough and sputum, have very little five-year decline in FEF2575%. On the other hand, one woman with no cough or sputum had a marked fall in FEF25-75%. An analysis of symptoms and the change in Dss showed a similar lack of relationship. There was no correlation between changes in pulmonary function over five years and the actual num-
710 WOOLF, ZAMEL
her of cigarettes smoked during this same period. The percentage of change in FEF25-75% is used as an example in Figure 2. Quite small changes in FEF2575% might be found in women who smoked as many as 80,000 cigarettes in five years, and relatively large changes might occur in women who had smoked less than 10,000 cigarettes during the same period. DISCUSSION
When the findings of the present study were examined, there were some expected results. ( 1) The great majority of nonsmokers remained clinically normal over the five-year period of observation. ( 2) Some smokers who entered the study without respiratory symptoms developed symptoms while under observation. ( 3) Over five years, there was a decrease in the results of tests which measure the flow of air. Changes in airflow were greater in smokers than nonsmokers. Changes in airflow were greatest in the group of smokers who had respiratory symptoms such as cough or sputum (or both), and this may be related to the greater number of cigarettes smoked by this group. On the other hand, there were a number of unexpected findings. ( 1) In spite of a consistent smoking habit, 18 percent of the smokers who entered the study with respiratory symptoms lost these symptoms by the end of the study. Similarly, Petty et al, 7
CHEST, 78: 5, NOVEMBER, 1980
Table 6--ClaaraceerUda of JO JF"omen JF"ho Slaowetl a Greater rlaan Normal Claa.,..e in Spirornetric Data FiH :rear• Initial Pulmonary Function Pack-Years on Admission to Study
Group, Subject, Age (yr), and Smoking Habit
Abnormal change in FEF25-753 1, 25, heavy 2, 41, heavy 3, 42, heavy 4,44,heavy 5, 48, heavy 6, 52, heavy 7, 53, moderate 8, 53, heavy 9, 53, light 10, 54, moderate 11, 54, heavy Normal change in FEF25-753; abnormal change in FEV1 12, 31, moderate 13, 34, heavy 14, 35, moderate 15, 36, light 16, 38, heavy 17, 41, moderate 18, 46, heavy Only abnormal change in FEV1/FVC 19, 44, heavy 20, 54, heavy
Cough or FEF Dss, Sputum FEV1/ 25-753, percent during of FVC, percent Study percent of normal normal
Cigarettes Smoked over 5 yr
-45* -55* -41* -61*
86 152 134
84 81 93 81 89 79 73
88 79 134 102 105 78 51
77
47 80
Both Acquired Lost Both Both Both Acquired Both Lost None &th.
78 91 84 81 91 76 87 81 75 93 88.
68 98 102 75 85 41 106
16 34
39,500 43,400 6,000 16,900 66,800 22,100 32,500
Both Acquired None None Both Both Lost
18 48
58,200 44,200
Both None
82
30
35 45 36 41 16 18 1 28 37 7 35 15 11
30
92
*Beyond 95 percent confidence level of normal nonsmokers of similar <t"-
""z C>
•
0
•
c
:c (.)
• • ••
•
•
•
-20
'# I&.
a
• -40
a
•
•
•
•
•
•
••
•
.
•
••
•
&.
•• ••
•
... .·-. . . . " . . .. ........ .. . .
••
•
-11 -22•
-44* -51* -57*
-10• -9 -9 -6 -26* -15* -20• 0 -4 -7 6 -22•
95 68 107 169 122 143 105
-26 -31 -26 -27 -36 -22 -27
-15* -15* -13* -11• -17* -12• -79*
-15* -11 -10 -9 -12 -11
89 152
-29 -29
-10 -1
-24* -23*
-so• -73* -52*
-so•
-24* -25* -37* -12 -19 -10 -16 -27*
-so•
•
• • •
FEV1 FEV1/FVC
•
•
+20
FEF 25-753
83 125 98 114 100 149 111 135 106 138 139 ..
53,500 40,000 66,500 56,200 39,800 49,400 28,300 51,700 7,800 21,300 59,300
12
Percent Change over 5 yr
• • ••
•••
• •• ••
•
·R • 0·09
•
•
• • • • • •
••
•• ••• •
• • • • •
•
• •
•
-60
•
•
•
•
• ••
• •
• 1,000
2®00 CIGARETTES
40,000
SMOKED
OVER
60l)OO
80,000
& YEARS
Fimnu: 2. For all smokers, change in FEF25-75S (or maximal midezpiratory flow rate CMMFJ over five years (as percentage of initial value) related to number of cigarettes smoked during same five years. R, Correlation coefBcient.
CHEST, 78: 5, NOVEMBER, 1980
RESPIRATORY EFFECTS OF REGULAR CIGARmE SMOKING IN WOMEN 711
in a follow-up study of 117 subjects with chronic bronchitis or asthma, noted that 13 smokers who initially had cough and sputum and who continued to smoke over a five-year period no longer had these symptoms at the time of reassessment. The reason for the loss of symptoms in smokers remains uncertain, but there may be some acquired resistance to the irritating effects of cigarette smoke. This is certainly seen in the beginning smoker who has considerable cough initially, which disappears with increased duration of smoking. ( 2) The loss of pulmonary ventilatory function over the years (both in absolute figures and percent change) in nonsmokers was not constant, becoming more rapid with increasing age. ( 3) There was no relationship between the number of cigarettes smoked and the amount of change in pulmonary ventilatory function. ( 4) There was no difference in gas exchange over five years (as shown by Dss on exercise) between nonsmokers and smokers, and there was no relationship between change in Dss and the number of cigarettes smoked. ( 5) Although there is a trend for a relationship between the rate of worsening of airflow and the presence of cough and sputum, there were often individual exceptions. Some women showed marked worsening of airflow in the absence of cough and sputum, and other individuals had cough and sputum and showed only insignificant changes in ventilatory function. It was expected that over the five years, ex-smokers might show a decrease in ventilatory function lying between the smokers and the nonsmokers. It was found that in all respects the ex-smokers resembled women who had been lifelong nonsmokers. The ex-smokers had very few respiratory symptoms, and this situation was maintained over the five years. Changes in pulmonary function during the period of observation were similar to the changes in the nonsmokers. This group of ex-smokers who stopped smoking before they developed serious pulmonary disease either had developed no evidence of obstruction to airflow by the time they stopped smoking, or they had shown recovery during their period of abstinence so that they were now indistinguishable from lifelong nonsmokers. There is the expected evidence of a dose-related response in that as a group, heavy smokers showed greater deterioration of ventilatory function than nonsmokers and light smokers, and moderate smokers were worse than light smokers; however, individual susceptibility also plays an important role in determining the effects of cigarette smoking. Individuals may react to cigarette smoke by evidence of irritation of the airways in the form of symptoms such as cough and sputum. Others may show suscep-
712 WOOLF, ZAMEL
Table 7-Claanse in FEFJS-75% Relaled 10 Pruenee or ..46aence o/ COIUUaena and Sputum /or Fi11e l'ear• in Smolcera •
c-•"
Change in
FEF25-75%, percent ..
Cough and Sputum Absent
Cough and Sputum Present
<20 percent
20
9
20-40 percent
17
14
>40 percent
4
-rable values are numbers of subjects.
••change expressed as percent of initial value. tibility as rapid worsening of ventilatory function but may remain symptomless; however, there is a tendency for both cough and sputum and rapid worsening of ventilatory function to exist together. Therefore our prospective study of Canadian women over a five-year period agrees with the conclusions of the eight-year prospective study of London men by Fletcher et al. 8 Fletcher et al8 suggested that smokers who stopped smoking did not recover ventilatory function but remained at a lower level of pulmonary function than nonsmokers, although pulmonary function worsened over the years at the same rate as nonsmokers. Possibly our group of women were different from the men studied by Fletcher et al8 in having no significant disability, and we found that the ex-smokers could not be distinguished in any way from the nonsmokers. We found that smokers without serious disability who stopped smoking behaved like lifelong nonsmokers, had a very low prevalence of respiratory symptoms, and showed worsening of pulmonary function similar to that of nonsmokers due simply to the process of aging. Fifteen percent (ten) of the female smokers over the age of 40 years showed a change in FEF25-75S over a five-year period that was greater than the expected change for normal nonsmokers. Most of these individuals could not be identified by the initial tests of pulmonary function, although, except for one, they were all moderate or heavy smokers and usually had cough or sputum. There were 24 heavy smokers over 40 years of age whose change in FEF25-75S was the same as nonsmokers, and this group had a smoking history of 28.4 + 11.8 packyears (mean ± SD). For comparison, the ten smokers over 40 years of age who had a greater change than normal in FEF25-75% had a smoking history of 28.7 + 13.4 pack-years (mean + SD). Therefore, there were two groups of women of similar age and similar exposure to smoking but different changes in FEF25-75S over a five-year period. This suggests that, in addition to the effects of the dose of smoking, there is a factor of individual susceptibilCHEST, 78: 5, NOVEMBER, 1980
ity; however, it is possible that the abnormal change in FEF25-75% in these ten women is an expression of the variability of the test It would have been helpful if the original baseline and five-year studies had been done on more than one occasion, but this was not practical in our study. Extending observation over ten years would also give results in individuals which would be more definite. Our data, at least, suggest a possibility of detecting susceptible individuals, and further studies would be useful to confirm our impressions. Fifteen percent of the female smokers between the ages of 25 and 54 years showed changes in FEF25-75~ or FEV1 or FEV1/FVC over a five-year period that were greater than the expected change for normal nonsmokers. These are simple tests of pwmonary function which could be repeated every five years in female smokers. Women who show an abnormally great change over this period might be considered to have a special susceptibility to the respiratory effects of cigarette smoke. These women might be at risk of developing future serious disability from chronic obstructive pulmonary disease. If these susceptible individuals could be detected before they develop serious disability and ifthey could be persuaded to stop smoking, then they might be expected to behave like lifelong nonsmokers. If this can be achieved, it is likely that the number of smokers who develop severe disability from chronic obstructive pulmonary disease will be much reduced. Of course, every effort should be made to discourage smoking in general, because of the many adverse effects other than the causation of obstructive pulmonary disease. The data obtained in the normal nonsmokers over five years may be useful for comparison with young women who possibly have a higher risk of developing chronic obstructive pulmonary disease than the smokers of the present study. These women may
CHEST, 78: 5, NOVEMBER, 1980
include individuals with different types of cwantitrypsin globulin and workers exposed to potentially noxious environments. ACKNOWLEDGMENT: Dr. J. T. Suero made an important contribution to this study. We thank Mrs. M. Brukst8ins, Mr. R. Hannah, Mr. W. Johnson, Mrs. P. Maclean, and Mrs. M. Leroux for technical assistance and Mrs. B. Fisher and Miss J. Emes for secretarial assistance. Mrs. M. McClellan was the public health nurse who :eerformed all of the follow-up assessments. Mrs. B. Kuzin did all of the statistical analyses. Guidance in the design of the f1~~ was provided by Professor W. Reid. We particularly the volunteers who took part in the investigation. The work was made possible by the cooperation of Dr. J. H. Baillie (Bell Telephone Co. of Canada); Dr. D. Grant (Ontario Hydro Electric Co.; Drs. G. Fowler, F. D. Kemper, and C. G. Preece (ImSinclair, perial o· Co.; Mrs. I. Lister (Ontario Heart Foundation); Dr. A. Parks (Canada Life Assurance Co.; Dr. J. D. Lovering (Gulf Oil); Dr. D. J. Breithaupt (Manufacturers' Life Assurance Co.); and Dr. J. Cole (North American Life Assurance Co. ) .
J·
1 Woolf CR, Suero JT. The respiratory effects of regular cigarette smoking in women. Am Rev Respir Dis 1971; 103:26-37 2 Woolf CR. Clinical 6ndings, sputum examinations, and pulmonary function tests related to the smoking habit of 500 women. Chest 1974; 66:652-9 3 How much did you smoke? (annotation). Lancet 1966; 1:648 4 Bates DV. The measurement of the pulmonary diffusing capacity in the presence of lung disease. J Clin Invest 1958; 37:591-605 5 Lawther PJ, Apthorp GH. Method for determination of carbon monoxide in blood. Br Jr Industr Med 1955; 12:326-9 6 Fletcher CM. The clinical diagnosis of emphysema. Proc Roy Soc Med 1952; 45:577-8'4 7 Petty TL, Pierson DJ, Dick NP, Hudson L, Walker S. Changes in FEV1 /FVC over about nine years: follow-up evaluation of a prevalence study for chronic bronchitis and chronic airway obstruction. Am Rev Respir Dis 1976; 114:881-90 8 Fletcher CM, Peto R, Tinker C, Speizer F. The natural history of chronic bronchitis and emphysema. Oxford, England: Oxford University Press, 1976
RESPIRATORY EFFECTS OF REGULAR CIGARETTE SMOKING IN WOMEN 713
Study
Colin R. Woolf. M.D.• F.C.C.P., and Noe Zamel. M.D.• F.C.C.P. Over a ftve-year period a consistent habit of smoking or nonsmoking was maintained by 302 women (aged 25 to 54 years at the beginning of the stndy). There were 130 nonsmokers, 40 u-smokers, and 15 light, 46 moderate, and 71 heavy smokers. Smokers without serious disabmty who had stopped smoking had a very low prevalence of respiratory symptoms and showed worsening of pulmonary function over the years similar to Hfe-long nonsmokers. Although there Is a dose-related response to cigarettes, individual susceptibDity also plays an impor·
A previous retrospective study of 500 women showed an increase in respiratory symptoms with an increase in the number of cigarettes smoked. Pulmonary ventilatory function, as well as diffusing capacity during exercise, showed lower results in smokers than in nonsmokers. 1•2 The results of a retrospective study of this type may not be accurate because the memory of the number of cigarettes smoked beyond five years is unreliable. 8 Of the original group, 302 women maintained a consistent habit of smoking or nonsmoking and were seen regularly over a five-year period. The purpose of this prospective study was to examine changes in clinical findings and in pulmonary function over a five-year period during which the number of cigarettes smoked had been accurately recorded. The present investigation provides a range for change in ventilatory function over a five-year period in apparently healthy nonsmoking women. Using this range, it is possible to identify susceptible smokers who show a deterioration in ventilatory function that is more rapid than normal. This type of susceptibility is not directly related to either the presence of respiratory symptoms or the number of cigarettes smoked. We found that smokers without serious disability who stopped smoking behaved like lifelong nonsmokers. We suggest that repeated spiromebic studies might be used to identify the susceptible smokers at an early stage. °From the Tri-hospital Respiratory Service and the Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Supported in part by a grant from the American Medical Association Education and Research Foundation. Manuscript received June 27; revision accepted December 10. Reprint requests: Dr. Woolf, CW.2-.200 College Wing, Toronto General H081Jital. Toronto, OntariO, Canada MSG
1L7
CHEST, 78: 5, NOVEMBER, 1980
tant role in determining the respiratory dect of smoking. A range for change in ventilatory function over a ftveyear period in apparently healthy nonsmoking women Is provided. Using this range, it Is polllble to identify susceptible smokers who show deterioration in ventllatory function that is more rapid than normal Repeated splrometric studies may be useful In selecting a group at greatest risk of developing later disabling- chronic obstructive pulmonary disease.
MATERIALS AND METHODS
The women for this study were volunteers who came mainly from large commercial firms, and all subjects considered themselves normal; that is, even if they had symptoms, they were not of a severity to require medical care. Only women between the ages of 25 and 54 years were accepted into the initial year of the study. At the time when this study commenced (over ten years ago), it was not appreciated that even younger female smokers might show signi6cant abnormalities of pulmonary function. Older women were not included because of concem that by the time that a further five years had passed, there might be an increasing number of complicating medical abnormalities. The women who took part in the prospective study were all examined initially as part of a retrospective study which has been fully described.1,2 The women were divided into five groups according to their average smoking habit over the five years of observation. Nonsmokers were those who had never smoked cigarettes. Ex-smokers had not smoked for at least one year before entrance into the study and remained nonsmokers. Light smokers were those who smoked 70 or fewer cigarettes per week, moderate smokers smoked 71 to 140 cigarettes per week, and heavy smokers smoked more than 140 cigarettes per week. There were 130 nonsmokers, 40 ex-smokers, and 15 light, 46 moderate, and 71 heavy smokers. The average age, duration of smoking on entrance into the study, and the average number of pack-years are shown in Table 1. Using analysis of variance, there was no significant difference in the mean ages of the groups. Only women who remained nonsmokers or remained smokers over the five years were included. Also, the smokers were excluded if they changed their year-by-year smoking by more than one group; for example, light smokers might become moderate smokers, but they would be excluded if they became heavy smokers. Similarly, a heavy smoker might become a moderate smoker, but if she became a light smoker, then she would be excluded. In fact, the smokers maintained a remarkable constancy for the weekly number of cigarettes smoked. The ex-smokers were only included if they had not smoked for at least one year before entering the study, and therefore the exsmokers had not smoked for at least six years by the end of
RESPIRATORY EFFECTS OF REGULAR CIGARETTE SMOKING IN WOMEN 707
Table I-Mean A••• Duration o/ Smoldq, anti Paclc·'Y-ra on Enlranee inlO S1r&d7* Group
No.
Age, yr
40.2±0.7
40
41.3±1.2
15.0±1.4
11.5±1.4
Smokers Light .. 15 Moderatet 46 Heavyi 71
43.2±1.7 39.1 ±1.1 38.6±0.9
16.7±1.6 18.0±1.0 17.5±0.9
5.2±0.8 15.0±0.9 23.7±1.4
Total
ConsisConsistently tently Absent Present
Duration of Smoking, yr Pack-Years
Nonsmokers 130 Ex-smokers
Table 2-Cluinse in S7mpeoma ONr FiH 'Yeara•
0
0
302
*Mean± SE. **Seventy cigarettes or less per week. tSeventy-one to 140 cigarettes per week. iMore than 140 cigarettes per week. the investigation. All of the women were seen once per year by the same specially trained public health nurse, and a special questionnaire was completed, with particular emphasis on an accurate history of smoking and the presence or absence of respiratory symptoms. At the end of &ve years, a full clinical examination and tests of pulmonary function were performed, as on the initial visit. The tests of pulmonary function were selected to give information about the abnormalities likely to result from smoking. These tests had shown important differences between smokers and nonsmokers in the previous retrospective studies.1,2 The tests were selected also on the basis of causing the least discomfort, in order to maintain the volunteer group over five years. Forced vital capacity ( FVC), forced expiratory volume in one second ( FEV1 ), and the mean forced expiratory flow during the middle half of the FVC (FEF25-751; formerly maximal midexpiratory flow rate) were calcu1ated from the best of at least three singlebreath tracings recorded using a water-sealed spirometer (Stead-Wells). A treadmill exercise test was performed at 1.5 mph at a 4 percent grade. Measurements for calculation of steady-state pulmonary diffusing capacity for carl>on monoxide ( Dss) were made during the fifth minute of exercise.• After the exercise test, the back pressure from carbon monoxide was measured by a rebreathing method, and an appropriate correction was made in the calculation of Dss.G The women had not smoked for at least two hours before the beginning of the tests of pulmonary function. The same tests using the same equipment were done initially and at the end of five years. To examine differences among the various groups, an analysis of variance was performed, and further comparisons were made using multiple t-tests.
Developed
Lost
Cough or sputum (or both) Nonsmokers 105 (81) Ex-smokers 34 (85) Smokers 37 (28)
7 (5) 0 50 (38)
12 (9) 5 (13) 21 (16)
6 (5) 1 (3) 24 (18)
Dyspnea•• Nonsmokers Ex-smokers Smokers
114 (88) 30 (75) 81 (61)
4 (3) 0 11 (8)
3 (2) 3 (8) 17 (13)
9 (7) 7 (18) 23 (17)
Wheeze Nonsmokers Ex-smokers Smokers
114 (88) 36 (90) 58 (44)
4 (3) 2 (5)
5 (4) 2 (5) 14 (11)
7 (5) 0 24 (18)
36 (27)
*Table values are numbers of subjects; numbers within parentheses are percents of group. **Grade 2 or 3 of Fletcher.•
Smokers frequently had symptoms, and those without symptoms initially, developed symptoms much more frequently than nonsmokers; however, it is of interest that 18 percent of the smokers lost symptoms during the five years, and this loss of symptoms occurred even though the number of cigarettes and the brand smoked during the five years remained constant. In no individual was there a change from nonfiltered to filtered cigarettes. Changes in pulmonary function after the five years of the study were related to the measurements at the initial visit. The result of a test on entering the study was subtracted from the result of that test at the end of five years, and the difference was expressed as a percentage of the initial value. As a first step, nonsmokers were compared with smokers. The FEF.25-75S (mean + SE) showed a greater decrease over five years in smokers ( -19.5 Table 3--Mean CU...e in Pulmonary' Function Ollf!Jr FiH 'Yean, Esprened aa Perce~e o/ lnitial J'alue* Group
FEV1••
FEVi/ FVCt
FEF
DBS
25-753*
(Exercise)
Nonsmokers -1.5±0.6 -6.4±0.5 -14.0±1.4 -5.9±2.8 Ex-smokers
The changes in symptoms over five years, comparing the initial and final visits, are shown in Table 2. Throughout the five years, most women remained either consistently without symptoms or with symptoms unchanged. Nonsmokers and ex-smokers initially had few symptoms, but some women developed symptoms, and in a few instances where symptoms were initially present, the women became symptomless by the time of the final examination. 708 WOOLF, ZAllEL
-0.8±0.8 -6.9±0.7 -15.0±2.2 -1.4±5.0
Smokers Light -0.4±1.7 -4.0±2.0 -18.8±5.2 -0.3±10.8 Moderate -3.0±1.9 -8.8±1.7 -17.4±2.0 -2.8±4.6 Heavy -4.6±0.8 -9.2±0.8 -21.0±2.1 -0.8±3.4 *Table values are mean percent changes ± SE. ••p <0.05 for heavy vs ex-smokers, for heavy vs light smokers, and for heavy vs nonsmokers. tP <0.05 for heavy VB nonsmokers, for heavy VB light smokers, and for moderate VB light smokers. iP <0.01 for heavy VB nonsmokers.
CHEST, 78: 5, NOVEMBER, 1980
Table 4--Mean C"--e in Pulmonary Function ONr
Fin Year•, Espreued a• Percenlqe o/ lnidal J"alue•
Smokers Cough or Sputum or Both
Data
Nonsmokers (No Cough or Sputum)
No Cough or Sputum
No. of subjects
105
37
50
FEV1
-1.1 ±0.7**
-1.7±0.9
-5.0±1.0••
FEV1/FVC
-6.2±0.6t
-6.8±0.8
-9.6±1.lt
FEF25-75%
-13.2±1.6t
-17.3±2.2
-23.9±2.5t
-6.8±3.0
-0.7±6.0
Dss
0.3±4.0
*Table values are mean percent changes ± SE. ..P<0.01. tP<0.05. tP<0.01.
±1.4 percent) than in nonsmokers ( -14.0 ± 1.4 percent; P < 0.01), and similarly the ratio of FEV1/ FVC showed a greater change in smokers ( - 8.5 ± 0.8 percent) than in nonsmokers ( -6.4 ± 0.5 percent P < 0.05). Comparisons were made between nonsmokers, exsmokers, and the smokers divided into smoking groups (Table 3). Between non-smokers and exsmokers, there were no significant differences in the results of any of the ventilatory tests over five years. The FEV1 showed a greater decrease for heavy smokers than for ex-smokers, light smokers, and nonsmokers (P < 0.05). The FEV1/FVC showed a greater fall in heavy smokers, compared with nonsmokers and light smokers; the moderate smokers showed a greater decrease in FEV1/FVC than the light smokers ( P < 0.05). The FEF25-75% showed a greater fall in heavy smokers than in nonsmokers (P < 0.01). The nonsmokers who remained without cough or sputum throughout the five years were compared with smokers, who were divided into groups depending upon the presence or absence of cough or sputum (Table 4). The FEV1, FEV1/FVC, and FEF25-75% all showed a greater fall over five years in smokers with consistent cough and sputum than in nonsmokers without these symptoms. Smokers without cough or sputum were not significantly different from either the nonsmokers or the smokers with cough or sputum (or both). The smokers without cough or sputum smoked, on the average, 31,668 ± 15,184 cigarettes (±SD) over the five-year period of observation. This was significantly less ( P < 0.01) than the average smoked by those with cough or sputum, namely, 41,236 + 12,584 cigarettes. Changes in Dss on exercise showed no significant differences over five years between nonsmokers, exsmokers and smokers, regardless of whether one
CHEST, 78: 5, NOVEMBER, 1980
divided smokers according to amount smoked or the presence or absence of symptoms (Tables 3 and 4). The mean change for nonsmokers was greater than for smokers; however, there was greater variability in the results in the smokers (note the high standard error of the mean), and comparisons of the means poorly represented the populations being considered. Changes in pulmonary function after five years in individual women were examined in relationship to age, presence of cough and sputum, and actual number of cigarettes smoked over five years. Pulmonary function changes at different rates, depending on age. As a standard, the results of linear regression analysis in nonsmokers are shown in Table 5. Older women changed more rapidly over the five years than the younger women. The percentage of change in FEF25-75% in all individual smokers and ex-smokers over five years as related to age on entering the study is shown in Figure 1. All ex-smokers fall within the normal range. Using a one-tailed distribution of the 95 percent confidence limit (dotted line in Fig 1 ) ,11 smokers ( 8 percent) fall below the limits of nonsmokers. The characteristics of this group are shown in Table 6. Ten of these women were over 40 years of age on entering the project (that is, 15 percent of the 67 smokers who were over 40 years of age). Most were moderate or heavy smokers with usually normal initial results on tests of pulmonary function. Symptoms of cough or sputum were variable. Similarly, the percentage of change in FEV1 and FEVi/FVC in all individual smokers and ex-smokers over five years as related to age on entering the study was analyzed. As for FEF25-75%, all ex-smokers fell within the range of nonsmokers. Using these tests, it was possible to identify, in addition to the 11 smokers with an abnormal change in FEF25-75%, a further seven smokers with a normal change in FEF25-75% but an abnormal change in FEV1, and Table 5--B.egreuion Equalioq /or Change in Pulmonary Function ( y) Ofler Fi11e Year• Related to Age (x) on Entering Study in NoR8n&olcer•
Test FEV1, ml Percent change
p SE of Regression Equation Estimate Value• y- -0.20:i:+6.42
160.1 6.18
<0.05 <0.01
FEVi/FVC, percent y- -0.19x+l.93 Percent change Y""' -0.23:i:+2.75
4.82 5.62
<0.01 <0.01
0.50 15.07
<0.01 <0.01
Y""' -4.4:i: +134.5
FEF25-75%, y= -0.014x+0.088 L/sec Percent change Y""' -o.oox+9.99 *Significance of slope from zero.
RESPIRATORY EFFECTS OF REGULAR CIGARmE SMOKING IN WOMEN 709
+40
• 0
+20 II.I
"cz %
•SMOKERS o EX-SMOKERS
•
•
•
•
•
0
•
8
u ~
-20
IL
2 2
-40
'~!>:
. :.
-··-·-·--•----- . •
•
•
-60 -80
•
•·Ji{·..
!a.·
0
~;-
•
•
• +-~~
......~~---~~---~~..-~
20
25
30
......~~--~~--
35
40
AGE• YEARS
!50
45
( Initial vesit)
Fromm 1. For all smokers and ex-smokers, change in FEF21S-75S (or maximal midexpiratory flow rate [MMF]) over five years (as percentage of initial value) related to age on entrance to study. Normal range is shown by one-tailed distribution of 95 percent confidence limit for nonsmokers (shaded area between aolid and broksn line&).
two others with only an abnormal change in FEV1/ FVC. The characteristics of these women are shown in Table 6 and are similar to those in the women identified by an abnormal change in FEF25-75%; however, five of the women with a normal change in FEF25-75% but an abnormal change in FEV1 were between the ages of 30 and 40 years. When all smokers were considered, 20 ( 15 percent) had an abnormal change in FEF25-75% or FEV1 or FEV1/ FVC over the five years of the study. In smokers the change in FEF25-75% as related to the presence or absence of consistent cough and sputum is shown in Table 7. Chi-square analysis shows no significant diflerence ( P > 0.1) between the number of women in whom cough and sputum were both absent or constantly present, regardless of the percentage of change in FEF25-75% over five years; however, from Table 7, one may also examine the relationship between symptoms and change in FEF25-75% in individual women. Table 7 shows that some women, in spite of consistent cough and sputum, have very little five-year decline in FEF2575%. On the other hand, one woman with no cough or sputum had a marked fall in FEF25-75%. An analysis of symptoms and the change in Dss showed a similar lack of relationship. There was no correlation between changes in pulmonary function over five years and the actual num-
710 WOOLF, ZAMEL
her of cigarettes smoked during this same period. The percentage of change in FEF25-75% is used as an example in Figure 2. Quite small changes in FEF2575% might be found in women who smoked as many as 80,000 cigarettes in five years, and relatively large changes might occur in women who had smoked less than 10,000 cigarettes during the same period. DISCUSSION
When the findings of the present study were examined, there were some expected results. ( 1) The great majority of nonsmokers remained clinically normal over the five-year period of observation. ( 2) Some smokers who entered the study without respiratory symptoms developed symptoms while under observation. ( 3) Over five years, there was a decrease in the results of tests which measure the flow of air. Changes in airflow were greater in smokers than nonsmokers. Changes in airflow were greatest in the group of smokers who had respiratory symptoms such as cough or sputum (or both), and this may be related to the greater number of cigarettes smoked by this group. On the other hand, there were a number of unexpected findings. ( 1) In spite of a consistent smoking habit, 18 percent of the smokers who entered the study with respiratory symptoms lost these symptoms by the end of the study. Similarly, Petty et al, 7
CHEST, 78: 5, NOVEMBER, 1980
Table 6--ClaaraceerUda of JO JF"omen JF"ho Slaowetl a Greater rlaan Normal Claa.,..e in Spirornetric Data FiH :rear• Initial Pulmonary Function Pack-Years on Admission to Study
Group, Subject, Age (yr), and Smoking Habit
Abnormal change in FEF25-753 1, 25, heavy 2, 41, heavy 3, 42, heavy 4,44,heavy 5, 48, heavy 6, 52, heavy 7, 53, moderate 8, 53, heavy 9, 53, light 10, 54, moderate 11, 54, heavy Normal change in FEF25-753; abnormal change in FEV1 12, 31, moderate 13, 34, heavy 14, 35, moderate 15, 36, light 16, 38, heavy 17, 41, moderate 18, 46, heavy Only abnormal change in FEV1/FVC 19, 44, heavy 20, 54, heavy
Cough or FEF Dss, Sputum FEV1/ 25-753, percent during of FVC, percent Study percent of normal normal
Cigarettes Smoked over 5 yr
-45* -55* -41* -61*
86 152 134
84 81 93 81 89 79 73
88 79 134 102 105 78 51
77
47 80
Both Acquired Lost Both Both Both Acquired Both Lost None &th.
78 91 84 81 91 76 87 81 75 93 88.
68 98 102 75 85 41 106
16 34
39,500 43,400 6,000 16,900 66,800 22,100 32,500
Both Acquired None None Both Both Lost
18 48
58,200 44,200
Both None
82
30
35 45 36 41 16 18 1 28 37 7 35 15 11
30
92
*Beyond 95 percent confidence level of normal nonsmokers of similar <t"-
""z C>
•
0
•
c
:c (.)
• • ••
•
•
•
-20
'# I&.
a
• -40
a
•
•
•
•
•
•
••
•
.
•
••
•
&.
•• ••
•
... .·-. . . . " . . .. ........ .. . .
••
•
-11 -22•
-44* -51* -57*
-10• -9 -9 -6 -26* -15* -20• 0 -4 -7 6 -22•
95 68 107 169 122 143 105
-26 -31 -26 -27 -36 -22 -27
-15* -15* -13* -11• -17* -12• -79*
-15* -11 -10 -9 -12 -11
89 152
-29 -29
-10 -1
-24* -23*
-so• -73* -52*
-so•
-24* -25* -37* -12 -19 -10 -16 -27*
-so•
•
• • •
FEV1 FEV1/FVC
•
•
+20
FEF 25-753
83 125 98 114 100 149 111 135 106 138 139 ..
53,500 40,000 66,500 56,200 39,800 49,400 28,300 51,700 7,800 21,300 59,300
12
Percent Change over 5 yr
• • ••
•••
• •• ••
•
·R • 0·09
•
•
• • • • • •
••
•• ••• •
• • • • •
•
• •
•
-60
•
•
•
•
• ••
• •
• 1,000
2®00 CIGARETTES
40,000
SMOKED
OVER
60l)OO
80,000
& YEARS
Fimnu: 2. For all smokers, change in FEF25-75S (or maximal midezpiratory flow rate CMMFJ over five years (as percentage of initial value) related to number of cigarettes smoked during same five years. R, Correlation coefBcient.
CHEST, 78: 5, NOVEMBER, 1980
RESPIRATORY EFFECTS OF REGULAR CIGARmE SMOKING IN WOMEN 711
in a follow-up study of 117 subjects with chronic bronchitis or asthma, noted that 13 smokers who initially had cough and sputum and who continued to smoke over a five-year period no longer had these symptoms at the time of reassessment. The reason for the loss of symptoms in smokers remains uncertain, but there may be some acquired resistance to the irritating effects of cigarette smoke. This is certainly seen in the beginning smoker who has considerable cough initially, which disappears with increased duration of smoking. ( 2) The loss of pulmonary ventilatory function over the years (both in absolute figures and percent change) in nonsmokers was not constant, becoming more rapid with increasing age. ( 3) There was no relationship between the number of cigarettes smoked and the amount of change in pulmonary ventilatory function. ( 4) There was no difference in gas exchange over five years (as shown by Dss on exercise) between nonsmokers and smokers, and there was no relationship between change in Dss and the number of cigarettes smoked. ( 5) Although there is a trend for a relationship between the rate of worsening of airflow and the presence of cough and sputum, there were often individual exceptions. Some women showed marked worsening of airflow in the absence of cough and sputum, and other individuals had cough and sputum and showed only insignificant changes in ventilatory function. It was expected that over the five years, ex-smokers might show a decrease in ventilatory function lying between the smokers and the nonsmokers. It was found that in all respects the ex-smokers resembled women who had been lifelong nonsmokers. The ex-smokers had very few respiratory symptoms, and this situation was maintained over the five years. Changes in pulmonary function during the period of observation were similar to the changes in the nonsmokers. This group of ex-smokers who stopped smoking before they developed serious pulmonary disease either had developed no evidence of obstruction to airflow by the time they stopped smoking, or they had shown recovery during their period of abstinence so that they were now indistinguishable from lifelong nonsmokers. There is the expected evidence of a dose-related response in that as a group, heavy smokers showed greater deterioration of ventilatory function than nonsmokers and light smokers, and moderate smokers were worse than light smokers; however, individual susceptibility also plays an important role in determining the effects of cigarette smoking. Individuals may react to cigarette smoke by evidence of irritation of the airways in the form of symptoms such as cough and sputum. Others may show suscep-
712 WOOLF, ZAMEL
Table 7-Claanse in FEFJS-75% Relaled 10 Pruenee or ..46aence o/ COIUUaena and Sputum /or Fi11e l'ear• in Smolcera •
c-•"
Change in
FEF25-75%, percent ..
Cough and Sputum Absent
Cough and Sputum Present
<20 percent
20
9
20-40 percent
17
14
>40 percent
4
-rable values are numbers of subjects.
••change expressed as percent of initial value. tibility as rapid worsening of ventilatory function but may remain symptomless; however, there is a tendency for both cough and sputum and rapid worsening of ventilatory function to exist together. Therefore our prospective study of Canadian women over a five-year period agrees with the conclusions of the eight-year prospective study of London men by Fletcher et al. 8 Fletcher et al8 suggested that smokers who stopped smoking did not recover ventilatory function but remained at a lower level of pulmonary function than nonsmokers, although pulmonary function worsened over the years at the same rate as nonsmokers. Possibly our group of women were different from the men studied by Fletcher et al8 in having no significant disability, and we found that the ex-smokers could not be distinguished in any way from the nonsmokers. We found that smokers without serious disability who stopped smoking behaved like lifelong nonsmokers, had a very low prevalence of respiratory symptoms, and showed worsening of pulmonary function similar to that of nonsmokers due simply to the process of aging. Fifteen percent (ten) of the female smokers over the age of 40 years showed a change in FEF25-75S over a five-year period that was greater than the expected change for normal nonsmokers. Most of these individuals could not be identified by the initial tests of pulmonary function, although, except for one, they were all moderate or heavy smokers and usually had cough or sputum. There were 24 heavy smokers over 40 years of age whose change in FEF25-75S was the same as nonsmokers, and this group had a smoking history of 28.4 + 11.8 packyears (mean ± SD). For comparison, the ten smokers over 40 years of age who had a greater change than normal in FEF25-75% had a smoking history of 28.7 + 13.4 pack-years (mean + SD). Therefore, there were two groups of women of similar age and similar exposure to smoking but different changes in FEF25-75S over a five-year period. This suggests that, in addition to the effects of the dose of smoking, there is a factor of individual susceptibilCHEST, 78: 5, NOVEMBER, 1980
ity; however, it is possible that the abnormal change in FEF25-75% in these ten women is an expression of the variability of the test It would have been helpful if the original baseline and five-year studies had been done on more than one occasion, but this was not practical in our study. Extending observation over ten years would also give results in individuals which would be more definite. Our data, at least, suggest a possibility of detecting susceptible individuals, and further studies would be useful to confirm our impressions. Fifteen percent of the female smokers between the ages of 25 and 54 years showed changes in FEF25-75~ or FEV1 or FEV1/FVC over a five-year period that were greater than the expected change for normal nonsmokers. These are simple tests of pwmonary function which could be repeated every five years in female smokers. Women who show an abnormally great change over this period might be considered to have a special susceptibility to the respiratory effects of cigarette smoke. These women might be at risk of developing future serious disability from chronic obstructive pulmonary disease. If these susceptible individuals could be detected before they develop serious disability and ifthey could be persuaded to stop smoking, then they might be expected to behave like lifelong nonsmokers. If this can be achieved, it is likely that the number of smokers who develop severe disability from chronic obstructive pulmonary disease will be much reduced. Of course, every effort should be made to discourage smoking in general, because of the many adverse effects other than the causation of obstructive pulmonary disease. The data obtained in the normal nonsmokers over five years may be useful for comparison with young women who possibly have a higher risk of developing chronic obstructive pulmonary disease than the smokers of the present study. These women may
CHEST, 78: 5, NOVEMBER, 1980
include individuals with different types of cwantitrypsin globulin and workers exposed to potentially noxious environments. ACKNOWLEDGMENT: Dr. J. T. Suero made an important contribution to this study. We thank Mrs. M. Brukst8ins, Mr. R. Hannah, Mr. W. Johnson, Mrs. P. Maclean, and Mrs. M. Leroux for technical assistance and Mrs. B. Fisher and Miss J. Emes for secretarial assistance. Mrs. M. McClellan was the public health nurse who :eerformed all of the follow-up assessments. Mrs. B. Kuzin did all of the statistical analyses. Guidance in the design of the f1~~ was provided by Professor W. Reid. We particularly the volunteers who took part in the investigation. The work was made possible by the cooperation of Dr. J. H. Baillie (Bell Telephone Co. of Canada); Dr. D. Grant (Ontario Hydro Electric Co.; Drs. G. Fowler, F. D. Kemper, and C. G. Preece (ImSinclair, perial o· Co.; Mrs. I. Lister (Ontario Heart Foundation); Dr. A. Parks (Canada Life Assurance Co.; Dr. J. D. Lovering (Gulf Oil); Dr. D. J. Breithaupt (Manufacturers' Life Assurance Co.); and Dr. J. Cole (North American Life Assurance Co. ) .
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1 Woolf CR, Suero JT. The respiratory effects of regular cigarette smoking in women. Am Rev Respir Dis 1971; 103:26-37 2 Woolf CR. Clinical 6ndings, sputum examinations, and pulmonary function tests related to the smoking habit of 500 women. Chest 1974; 66:652-9 3 How much did you smoke? (annotation). Lancet 1966; 1:648 4 Bates DV. The measurement of the pulmonary diffusing capacity in the presence of lung disease. J Clin Invest 1958; 37:591-605 5 Lawther PJ, Apthorp GH. Method for determination of carbon monoxide in blood. Br Jr Industr Med 1955; 12:326-9 6 Fletcher CM. The clinical diagnosis of emphysema. Proc Roy Soc Med 1952; 45:577-8'4 7 Petty TL, Pierson DJ, Dick NP, Hudson L, Walker S. Changes in FEV1 /FVC over about nine years: follow-up evaluation of a prevalence study for chronic bronchitis and chronic airway obstruction. Am Rev Respir Dis 1976; 114:881-90 8 Fletcher CM, Peto R, Tinker C, Speizer F. The natural history of chronic bronchitis and emphysema. Oxford, England: Oxford University Press, 1976
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