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Pulmonary Function in Former Alcoholics
Pulmonary Function in Former Alcoholics* Cemil Emirgil, M.D., F.C.C.P.,•• and Bruce]. Sobol, M.D., F.C.C.P.t
Pulmonary function was evaluated in 44 former alcoholics (abstinence, 0.5 to 32 years) without cardiac or specific pulmonary disease. All were members of Alcoholics Anonymous. Fourteen subjects (32 percent) were nonsmokers, ex-smokers, and cigar or pipe smokers, yet 28 subjects (64 percent) bad abnormal expiratory flow rates, and 17 (39 percent) bad an elevated value for the ratio of the residual volume to the total lung capacity. Single-breath diffusing capacity was abnormal in seven subjects (16 percent). Of interest was the bigb incidence
The common clinical impression that there is a high prevalence of nonspecific pulmonary disease among chronic alcoholics has recently been confirmed. 1.2 The characteristic functional abnormalities are airway obstruction and impainnent of diffusion, both of which are almost universally present. In contradiction to the generally held view, these abnormalities in function cannot be explained on the basis of cigarette smoking and frequent pulmonary infections. On the contrary, these studies suggested that functional abnormalities, at least in part, might be caused by alcohol per se. It was also shown that short periods ( ie, up to three weeks) of abstinence had no significant effect on the observed abnormalities; t.2 however, it is not known whether the deleterious effects of excessive ingestion of alcohol are permanent, regress, or disappear entirely with long periods of abstinence. A knowledge of the pulmonary function of former alcoholics could shed light on the relationship between chronic alcoholism and chronic pulmonary disease. This study presents data on former alcoholics and compares their pulmonary function with that of alcoholic patients previously studied and reported.2 °From the Cardiopulmonary Laboratory, Westchester County Medical Center ( Grasslands Hospital), and the Department of Medicine, New York Medical College, Valhalla, NY. Presented in part at the NCA-AMSA Medical/Scientific Meeting in Washington, D.C., May 6-8, 1976. With the assistance of Ms. Lyrmea Van Voorhies, Ms. Kathleen Palmer, and Ms. Deborah Pomier. Supported in part by the Westchester Heart Association. • • Associate Professor of Medicine. tProfessor of Medicine. Manuscript received June 11; revision accepted October 1. Reprint requests: Dr. Emirgil, Pulmo!liJ!JI Lizboratory, Westchester Count11 Medical Center, Valhalla, New York 10595
CHEST, 72: 1, JUlY, 1977
(17 percent) of obstructive phenomena among the women. This bigb incidence of abnormalities among both the men and women could not be attributed to previous pulmonary infection or smoking. Comparison of these patients with chronic alcoholics suaests that the obstructive component In these patients is, in part, a result of their past alcoboHc Intake and that it is not reversed by abstinence. On the other band, the impairment in diffusion, which was so common In alcoholics, appears to be reversible with sobriety.
MATERIAI.S AND METHODs
The subjects were chosen from members of Alcoholics Anonymous. This appeared to be the best way of assuring sobriety. Three local chapters with a sufficiently large membership ( 124 people) were chosen. The 103 members present at the chapter meetings were given a letter explaining the study and asking them to fill out a questionnaire. They were asked to return the questionnaire whether or not they were willing to participate in the study. To be included in the study, all subjects had to have imbibed excessively for eight years or longer, followed by a period of abstinence of six months or longer. They had to be willing to have a physical examination, chest x-ray film, and electrocardiogram, to perform tests of pulmonary function, and to permit a venipuncture. A minimum of eight years of chronic alcoholism was used as a criterion with the hope that the subjects in the present study would be comparable with the chronic alcoholics in the previous study with respect to consumption of alcohoJ.2 Eighty-four ( 82 percent) of the members responded. Of these, seven ( 8 percent) refused to participate in the study, and 20 ( 24 percent) did not meet the criteria. The remaining 57 subjects met the criteria and were willing to participate. Tiley were paid to compensate for their time and inconvenience, and all signed an informed consent. The study extended over a period of three months. After all of the data were obtained, 13 subjects were excluded for the following reasons: one had bronchial asthma; two had anabnormalECG; one had a slightly enlarged heart; three had pulmonary lesions on the chest x-ray film; and six had a history of drug addiction. The remaining 44 subjects without cardiac or specific puhnonary disease (tuberculosis, bronchiectasis, sarcoidosis, etc) formed the basis of this study. None of these subjects had been studied before or included in the previous study.2 The form used for the medical history was the standard British Medical Research Council Questionnaire. In addition, a detailed history of alcohol ingestion was obtained from all subjects. In order to compare the different types of alcohol, beer was considered to contain 4 percent alcohol, wine 12 percent, and hard liquors 45 percent. In this study,
PULMONARY FUNCnON IN FORMER ALCOHOLICS 45
the term, "pint," then refers to 16 oz of hard liquor, 60 oz of wine, and 180 oz of beer. Habits of smoking and drinking were recorded in terms of duration and daily consumption, and each was converted to pack-years or pintyears. Smokers who stopped smoking at least six months ·prior to the study were classified as ex-smokers. A sample of venous blood was obtained from every subject for automated analysis (SMA-12) of blood chemistry ( levels of calcium, glucose, inorganic phosphate, creatinine, uric acid, cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, lactic dehydrogenase, and serum glutamic-oxaloacetic transaminase); for a hematocrit reading, and for determinations of At-antitrypsin level. The serum level of At-antitrypsin was determined by radial immunodiffusion, with reagents obtained from a commercial supplier ( Behring Diagnostics). The chest x-ray film and ECG were interpreted by a roentgenologist and cardiologist who did not know the subjects or the results of the studies of pulmonary function. Spirometric studies were performed on a waterless spirometer (Jones Pulmonor) with the subject in the sitting position. The expiratory curves were analyzed for vital capacity ( VC), forced vital capacity ( FVC), the forced expiratory volume in one second ( FEV t ) , the ratio of FEV JIFVC, and the mean forced expiratory flow during the middle half of the FVC ( FEF25-75$). The highest value of three or four determinations was used. The functional residual capacity ( FRC) and the airway resistance ( Raw) were measured by body plethysmographic studies, as previously describedS and subsequently modified.• Specific conductance (Gaw/VL) was determined at the lung volume at which Raw was measured. The expiratory reserve volume ( ERV) was determined by spirometric studies. This value, together with the VC and FRC, permitted the calculation of total lung capacity ( TLC), residual volume ( RV), and the ratio of RV/TLC. The single-breath diffusing capacity for carbon monoxide ( Dsb) was determined by the method of Ogilvie and co-workers.' The predicted values for RV, TLC, and RV/TLC for male subjects were obtained from Boren et al. • These values for RV and TLC for female subjects were obtained from Goldman and Becklake. 7 The normal value for RV/TLC for female subjects was assumed to be the same as for male subjects. Normal values for Dsb were obtained from studies of 114 male and 58 female healthy subjects. Smokers and ex-smokers were not excluded (the study was done by Abraham S. Kuperman, M.D., at the Albert Einstein College of Medicine, Bronx, NY). Predicted values for Dsb were calculated from the following two formulas (where height was expressed in centimeters) : ( 1 ) for patients less than 35 years of age, Dsb =Heigh~ X 6/10' ± 6.6; and ( 2) for patients more than 34 years of age, Dsb =Heigh~ (804- 6 Age)/10S ± 6.6. The predicted values and limits of normal for the VC, FEVt, FEV1/FVC, and FEF25-75$ were determined by criteria previously published.• In all instances the standard error of the estimate (SEE) was multiplied by 1.64 and added to or subtracted from the predicted value. A common method of determining the limits of normal is to use the predicted value ± 2 SEE. This eliminates 5 percent of the normal population, ie, 2.5 percent from both the upper and lower tail of the normal distribution curve; however, in tests of ventilatory funCtion, abnormality exists only at one end of the distribution curve. Therefore, to eliminate 5 percent from this end, 1.64 SEE is used. • The statistical significance of observed diHerences was determined by the use of the
48 EMIRGIL, SOBOL
Student's t-test. A value for probability of less than 0.05 was considered significant. REsULTS
The clinical data are given in the following tabulation, showing the numbers of subjects (numbers within parentheses are percentages) : Total subjects
44
Sex Male Female
25 (57) I9 (43)
Smoking Cigarette Cigar Pipe Ex-smoker Nonsmoker
30 (68) I (2) I (2)
8 (18) 4 (9)
Chronic bronchitis (clinical)
IS (4I)
Total subjects with symptoms
26 (59)
The percentage of subjects by sex in our sample approximated the percentage in the three chapters of Alcoholics Anonymous. Fourteen ( 32 percent) of the subjects were nonsmokers, ex-smokers, or pipe and cigar smokers. Eleven subjects ( 25 percent) had a palpable liver (one to two fingerbreadths). With the exception of slightly elevated concentrations of ·alkaline phosphatase in 16 subjects, the results of automated studies (SMA-12) of blood chemistry were within the limits of normal; however, there was no relationship between the elevated concentration of alkaline phosphatase and a palpable liver. The serum level of at-antitrypsin was normal in all but one subject. This person was a heterozygote and had normal pulmonary function. The mean hematocrit reading was 43 ± 4 percent, and values ranged from 36 to 49 percent. Twentysix subjects (59 percent) had respiratory symptoms, and 18 ( 41 percent) had chronic bronchitis based on the standard British Medical Research Council Questionnaire. Dyspnea was the only symptom in eight subjects. Thirteen subjects ( 30 percent) gave a history of having 18 episodes ( 1.3 episodes per subject) of acute bronchitis or pneumonia or both. During the past three years, only one subject had one episode of pneumonia, and one subject had one episode of acute bronchitis. Additional clinical data and the results of studies of pulmonary function are listed in Table 1. The Cigarette smoking, drinking habits, age, and duration of sobriety varied very substantially. During the period of sobriety, seven subjects increased, ten decreased, and 12 did not change their consumption of cigarettes. There was a very slight decrease in the total consumption of the 30 current smokers.
CHEST, 72: 1, JULY, 1977
Table l-Pulmonary Function and CUnical Data from 44 Former Akolaoliu
Measurement
Table 2--Dala from 13 Female Former Akolaolic Smolcer•
No. with Abnormal Results Mean±SD Range (percent)
Age, yr
47±9
32-71
Alcohol Pint-years• Duration of consumption, yr
28±15 22±9
7-66 9-43
Measurement
No. with Abnormal Results Mean±SD Range (percent)
Age, yr
47±9
34-67
VC, percent of predicted
96±13
82-125
0
FEV., percent of predicted
89±16
67-130
3 (23)
FEV./FVC, percent
75±6
~
6 (46)
FEF25-75%, percent of predicted
58±26
30-116
10 (77)
Dab, percent of predicted
85±13
~112
2 (15)
RV /TLC, percent of predicted 145±26
96-195
7 (54)
Smoking•• Pack-years Duration, yr
39±20 28±11
5-82 9-43
Sobriety, yr
5.7±6.3
0.5-32
VC, percent of predicted
97±13
71-125
2 (5)
FEV., percent of predicted
86±20
34-130
13 (30)
Smoking, pack-years
33±19
5-77
FEV./FVC, percent
72±12
32-88
23 (52)
Consumption of alcohol, pint-years•
16±9
6-36
Sobriety, mo
52±36
8-108
FEF25-75%, percent of predicted Gaw/VL, L/sec/cm H,O/Lt TLC, percent of predicted
59±26
8-116 28 (64)
0.20 ±0.13 0.04-0.53 14 (32) 102±12
81-145
2 (5)
RV /TLC, percent of predicted 130±32
75-230
17 (39)
Dab, percent of predicted
51-135
7 (16)
92±21
*See "Materials and Methods" for definition of pint-years.
••as subjects (current cigarette smokers and ex-smokers). tNormal value,
> 0.16.
During the first year of sobriety, nine subjects stopped smoking cigarettes completely. Of these, eight were classified as ex-smokers. The average abstinence from smoking was three years, and the duration varied from six months to ten years. There was no significant difference between the ex-smokers and smokers with respect to cigarette consumption ( P > 0.3) and expiratory flow rates ( P > 0.5). Therefore, ex-smokers were not analyzed as a separate group. Only two patients had an abnormal VC. These two patients had a normal TLC, severely impaired flow rates, and abnormally elevated RV /TLC, indicating that the reduced VC was not due to restrictive pulmonary disease. Using the FEF25-75% as the criterion, 28 subjects ( 64 percent) had chronic obstructive pulmonary disease. The incidence of an abnormal value for FEF25-75% was 70 percent ( 21 subjects) in the current smokers, 75 percent (three subjects) in nonsmokers, and 50 percent (four subjects) in ex-smokers. The subject who was a cigar smoker had moderate chronic obstructive pulmonary disease. The pulmonary function of the pipe smoker was normal. The FEVt!FVC was abnormal in 23 patients (52 percent) and was always associated with an abnormal FEF25-75%. The deCHEST, 72: 1, JULY, 1977
*See "Materials and Methods" for definition of pint-years.
gree of obstruction varied from mild to severe. More than one-third of the subjects ( 39 percent or 17 subjects) had abnormally elevated RV /TLC, and with one exception an abnormal RV /TLC was always associated with an abnormal FEF25-75%. Only seven subjects ( 16 percent) had an abnormal Dsb. No patient had an abnormally low TLC. The pulmonary function and clinical data on female former alcoholic smokers are summarized in Table 2. The FEF25-75'1, was abnormal in ten subjects (77 percent). Using the FEVt!FVC as the criterion, six subjects ( 46 percent) had chronic obstructive pulmonary disease. More than half (54 percent or seven) of these 13 subjects with impaired flow rates also had abnormally elevated values for RV/TLC. Table 3---Data from Female Former Akolaolic Non.molcen
Measurement
Case 1 Case 2 Case 3 Case 4
Age (yr), Sex
49, F 44, F 43, F 41, F
VC, percent of predicted
107
108
105
122
FEV1 /FVC, percent
68*
66*
80
80
FEF25-75 %, percent of predicted
55*
35*
65*
72
91
116
95
101
Dab, percent of predicted
111
RV /TLC, percent of predicted
145* 153*
117
Consumption of alcohol, pint-years••
11
28
13
27
Sobriety, mo
24
25
19
49
*Beyond the limits of normal. ••See "Materials and Methods" for definition of pint-years.
PULMONARY FUNCnON IN FORMER ALCOHOLICS 47
The clinical and pulmonary function data on the subjects who never smoked are shown in Table 3. This group consisted of four middle-aged women. The FEF25-75~ was abnormal in three subjects and the FEVt!FVC and RV/TLC in two subjects. DISCUSSION
The high prevalence of obstructive pulmonary disease and the low prevalence of an abnormal diffusing capacity in these former alcoholics is interesting and surprising. The results of the present study show that two common abnormalities of chronic alcoholics (namely, obstructive pulmonary disease and impaired diffusion) were affected differently by sobriety. It appears that abstinence from alcohol restored diffusion to normal but caused no improvement in the obstructive phenomenon. To determine to what extent previous alcohol Consumption is a contributing factor to the high prevalence of obstructive pulmonary disease, an attempt must be made to separate the effects of previous pulmonary infections and cigarette smoking from the effects of alcohol per se. In the present study the frequency of past chest illnesses per subject ( 1.3 episodes per person) did not differ significantly from that of an apparently healthy population. 2.11 Furthermore, all but two subjects had their chest illnesses many years prior to the present study. It has been shown that 1.3 episodes of past chest illness per person do not impair pulmonary function. 2•9 Therefore, it is reasonable to assume that past pulmonary infections are not the cause of abnormal function in these former alcoholics. Fourteen ( 32 percent) of the subjects were exsmokers, nonsmokers, and pipe or cigar smokers, yet the incidence of obstructive pulmonary disease was 64 percent ( 28 subjects). There were 30 current cigarette smokers. Of these, 21 ( 70 percent) had an abnormal FEF25-75~, and 16 (53 percent) had an abnormal FEVt!FVC. Although the role of cigarette smoking in the pathogenesis of obstructive pulmonary disease is well established, this high prevalence is difficult to explain on the basis of smoking alone. In the present study, male current cigarette smokers as a group can be classified as moderate to heavy smokers (average lifetime smoking of 14,000 packages). The FEF25-75~ was abnormal in 11 subjects (65 percent), and the FEVt!FVC was abnormal in ten (59 percent). The percentage of abnormal ventilatory function has been reported as being 25 percent in male moderate smokers 10 and 30 percent in male very heavy smokers (lifetime smoking of more than 18,000 packages) .11 An attempt was made to correlate pulmonary 48 EMIRGIL, SOBOL
function with smoking and alcoholic intake. Only expiratory flow rates correlated with the consumption of both cigarettes and alcohol; however, the correlations were too poor ( r < 0.4) to be meaningful. These poor correlations might be due to the fact that former alcoholics formed a nonhomogeneous group. There was no correlation between the consumption of alcohol and that of cigarettes. The duration and intake of alcohol did not correlate with the duration of sobriety. Sobriety was not related to smoking habits following the onset of abstinence; some subjects discontinued smoking, while others decreased or even increased their consumption of cigarettes. Although it would have been desirable to divide the subjects into groups with comparable exposure to alcohol and cigarette smoke and comparable duration of abstinence, this was not possible. No group of subjects was sufficiently large to make a valid comparison with another group with a different profile for consumption of alcohol and cigarettes and for abstinence. More than three-fourths ( 77 percent or ten) of the female smokers had abnormal expiratory flow rates. This was an unexpected finding. Although published reports show a statistically significant difference between the ventilatory function of female nonsmokers and heavy smokers, the magnitude of this difference is minor, and only a small percentage of female heavy smokers have abnormal flow rates. 12.1 3 An even more striking observation was the presence of chronic obstructive pulmonary disease in three out of four women who never smoked. The very high incidence of abnormal flow rates among female former alcoholics suggests that past
alcoholism must have played a role in the pathogenesis of their obstructive pulmonary disease. In addition, the equations of Grimes and Hanes 13 were used to correct the FEV1 and FEF25-75~ for smoking. Despite this correction, the FEV1 in 26 smokers ( 87 percent) and the FEF25-75~ in 25 smokers ( 83 percent) were less than predicted (Table 4). The difference between the observed and predicted values (corrected for smoking) was highly significant. Both the FEV1 and FEF25-75~ were abnormally low (predicted values-1.64 X SEE) in 14 subjects ( 47 percent) (Table 4). Although in a population of cigarette smokers, the effects of other toxic agents cannot be separated with certainty from the effects .of cigarette smoking, these observations suggest that smoking alone cannot account for the high prevalence of obstructive pulmonary disease among former alcoholics. To determine the role of alcohol in the pathogenesis of pulmonary disease in alcoholics, it is necessary to make comparisons between the functional CHEST, 72: 1, JULY, 1977
Table 4--Data on FEJ' 1 and FEF25-75% in 30 Current Ci«arelle Smolcer•
Measurement No. of subjects
Men
Women
17
13
FEV1 Observed, L (mean ± SD) 3.1 ±0.9 Predicted, L (mean ± SD)* 3.7±0.5 P value for observed vs predicted 0.005 No. with values less than predicted (percent)* 14 (82) 7 (41) No. with abnormal results (percent) FEF25-75% Observed, L (mean ± SD) 2.4±1.1 Predicted, L (mean ± SD)* 3.5±0.7 P value for observed vs predicted 0.001 No. with values less than predicted (percent) • 13 (76) No. with abnormal results (percent) 8 (47)
2.1 ±0.4 2.6±0.3 0.001 12 (92) 7 (54) 1.8±0.9 2.9±0.4 0.001 12 (92) 6 (46)
*Corrected for smoking.
abnormalities of alcoholics and former alcoholics. It will also be necessary to discuss briefly the effects of cirrhosis of the liver on pulmonary function, since chronic hepatic disease is known to alter a number of respiratory functions. To facilitate comparisons between alcoholics and former alcoholics, pertinent data from the previous study of alcoholics2 and the present study were summarized in Table 5. The mean age of the former alcoholics is slightly but significantly higher than that of the alcoholics; however, this difference in age has no effect on function, since pulmonary function is corrected for age. There· is no significant difference between alcoholics and former alcoholics with respect to consumption of alcohol ( P > 0.3) and cigarettes ( P > 0.6). The hematocrit readings were also listed, since the level of hemoglobin in the pulmonary capillaries affects diffusion. The hematocrit readings of two groups did not differ significantly ( P > 0.5). Therefore, both groups are similar with respect to consumption of alcohol and cigarettes imd with respect to the hematocrit reading. It can be seen from Table 5 that the common functional abnormality of alcoholics (namely, obstructive pulmonary disease) does not appear to be reversible with abstinence. As a group, there was no significant difference between alcoholics2 and former alcoholics with respect to the expiratory flow rates. Although the high incidence of chronic pulmonary disease in alcoholics is well accepted and recently documented, 1.2 little information exists with regard to the effects of alcohol on the lungs. Experimental studies in animals have shown that metabolites of alcohol accumulate in the lungs 14 and that intraperitoneally injected alcohol can produce histochemical alterations in the pulmonary tissue.15 It
CHEST, 72: 1, JUlY, 1977
has also been shown that alcohol reduces the clearance of inhaled bacteria from the lungs. 16.1 7 In alcoholics, a considerable amount of alcohol can reach the lungs without being metabolized by the liver, and this may produce a direct toxic effect on the lungs. Although there is no experimental evidence, metabolites of alcohol may also accumulate in the human lungs; however, the effects of alcohol metabolites on the lung is not known. Impaired clearance of bacteria from the lungs may make alcoholics more susceptible to chronic bronchial infections. It is conceivable that if the combined effect of alcohol and its metabolites and the depressed bacterial clearance can cause injury to pulmonary tissue, they might also make the lungs more susceptible to the injurious effects of cigarette smoking or other toxic agents. It is possible that once a certain degree of pulmonary injury takes place, function may not be restored to normal in spite of abstinence from consumption of alcohol. Table 5--Compariwm behCJeen Aleolaoliu* arul Former Aleolaolie•
Measurement
No. with Abnormal Results Mean±SD Range (percent)
Age, yr Alcoholics Former alcoholics
40±9** 47±9**
26-57 32-71
Consumption of alcohol, pint-yearst Alcoholics Former alcoholics
36±20t 28±15t
10-89 7-66
Smoking, pack-years Alcoholics Former alcoholics
42±25t 39±20t
14-101 5-82
Hematocrit reading, percent Alcoholics Former alcoholics
42±4t 43±4t
36-47 36-49
FEV./FVC, percent Alcoholics Former alcoholics
72±8t 72±12t
58-83 32-88
FEF25-75%, percent of predicted Alcoholics Former alcoholics
58±26t 59±26t
26-106 16 (70) 8-116 28 (64)
Dsb, percent of predicted Alcoholics Former alcoholics
66±16§ 92±21§
13 (57) 23 (52)
.. 39-104 51-135
14 (61) 7 (16)
*Data on alcoholics from Emirgil et al. 2 Number of alcoholics was 23 (four female and 19 male subjects); one was a nonsmoker, and 22 were cigarette smokers. **P = 0.005. tSee "Materials and Methods" for definition of pint-years. tNot significant. §P - 0.001.
PULMONARY FUNCTION IN FORMER ALCOHOLICS 49
The other common and puzzling abnormality of alcoholics is the unexplained impairment of diffusion.1.2 This abnormality appears to be reversible with abstinence (Table 5). In the previous study, 61 percent ( 14) of 23 chronic alcoholics had an abnormal Dsb. 2 This high incidence could not be attributed to anemia or cigarette smoking. None of the alcoholics had significant anemia, and even after a correction for smoking 18 was made, 40 percent (nine) of the patients remained with an abnormal Dsb. 2 These results are similar to those of Banner. 1 In the present study, only seven ex-alcoholics ( 16 percent) had an abnormal Dsb. There is a significant ( P < 0.001) and substantial difference between the mean percentage of the predicted value for Dsb of alcoholics ( 66 -+- 16 percent) and that of former alcoholics ( 92 ± 21 percent). This difference is not due to a difference in the smoking and drinking habits or the level of hemoglobin of the two populations. In addition, in both studies the same method for determining Dsb and the same equipment, prediction equations, and criteria of abnormality were used, and the same technician performed the test; however, there was one important difference between the two groups. The majority of chronic alcoholics had clinical and laboratory evidence of significant hepatic disease. In the present study, only a small percentage of the former alcoholics might have had mild hepatic disease. There are two possible explanations for the difference in Dsb: ( 1) Alcohol has a direct toxic effect on the lung and produces anatomic or physiologic changes, or both, which interfere with the process of diffusion; these changes are reversible, and abstinence from alcohol restores gas exchange to normal. ( 2) The impaired diffusion is secondary to alcoholic hepatic disease which, through some unknown mechanism, impairs gas exchange; abstinence from alcohol restores hepatic function to normal, and diffusion becomes normal. There are data in the literature to support both hypotheses. Accumulation of alcohol metabolites in the lungs 14 and histochemical changes in the pulmonary tissue secondary to intraperitoneal injection of alcohoP1 support the first hypothesis; however, the bulk of published work supports the second hypothesis. The occurrence of reduced diffusion in patients with cirrhosis of the liver has been well documented. 19-21 The impaired diffusion is not related to the etiology of the hepatic disease and can occur not only in patients with alcoholic hepatic disease but also in those with primary biliary cirrhosis and active chronic hepatic disease. 19-21 These observations strongly suggest that impaired diffusion is related to hepatic dysfunction. It has been postu50 EMIRGIL, SOBOL
lated that the combined effect of several abnormalities, such as increased capillary permeability, reduced colloidal osmotic pressure due to decreased plasma levels of albumin, and hormonal changes, in patients with hepatic disease can cause interstitial pulmonary edema, which may interfere with the process of diffusion. 2.2o It has also been suggested that the impaired diffusion may be the reflection of some pattern of pulmonary inhomogeneity. 19 Recent work has shown that regional abnormalities of ventilation and perfusion can occur in patients with cirrhosis of the liver; 20.22 however, the cause of the impairment of diffusion in chronic hepatic disease remains uncertain. Although in the present study, no subject could be diagnosed as having cirrhosis of the liver, some of them might have had mild alcoholic chronic hepatic disease, since 11 subjects had a palpable liver, and 16 had a slightly elevated concentration of alkaline phosphatase. Of the seven subjects who had abnormal diffusion, only two had a palpable liver. Of these, one had minimal obstructive pulmonary disease, and in the second, impaired diffusion was the only abnormality. It is possible that in these two subjects, impaired diffusion was secondary to hepatic disease. The remaining five subjects with abnormal diffusion had functional and roentgenographic evidence of moderate to severe pulmonary emphysema. These findings indicate that in the absence of hepatic disease, the impaired diffusion of former alcoholics is the result of pulmonary emphysema. There is one important consideration that should be mentioned. Although alcoholics and former alcoholics as a group were similar in important respects ( ie, consumption of cigarettes and alcohol and the hematocrit reading), the two groups might have been different in other characteristics. Therefore, comparisons between the two groups have limitations. The effect of sobriety for a given individual patient cannot be determined from these comparisons, since the pulmonary function of the subjects in the present study was not evaluated while they were alcoholics. It is possible that the impaired function of certain individuals may improve or be restored to normal with abstinence. It is also possible that once a certain degree of pulmonary injury takes place, the abnormal function of some alcoholics may progressively deteriorate, in spite of sobriety. In conclusion, the data show that former alcoholics have a high incidence of obstructive pulmonary disease, usually associated with an abnormally elevated RV /TLC and occasionally with an impaired Dsb. This high incidence suggests that obCHEST, 72: 1, JULY, 1977
structive pulmonary disease of former alcoholics is, in part, a result of their previous chronic alcoholism. ACKNOWLEDGMENT: We are indebted to Ms. Philomena Adinaro, Ms. Pattie Baskette, Ms. Catherine Doyle, Ms. Kathleen Kaplan, Ms. Sandra Kaplan, Ms. Trudy Singer, and Ms. Deborah Telesco.
1 Banner AS: Pulmonary function in chronic alcoholism.
Am Rev Respir Dis 108:851-857, 1973 2 Emirgil C, Sobol BJ, Heyman B, et al: Pulmonary function in alcoholics. Am J Med 57:69-77, 1974 3 DuBois A, Botelho S, Cornroe J: A new method for measuring airway resistance in men using a body plethysmograph: Values in normal subjects and in patients with respiratory disease. J Clin Invest 35:327-335, 1956 4 Sobol BJ: Methods for simplifying constant volume body plethysmograph. J Appl Physiol 27:259, 1969 1) Ogilvie C, Forster R, Blakemore W, et al: A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest 36:1-17, 1957 ~ Boren H, Kory R, Syner J: The Veterans Administration-Army cooperative study of pulmonary function: 2. The lung volume and its subdivisions in normal men. Am J Med 41:96-114, 1966 7 Goldman HI, Becklake MR: Respiratory function tests: Normal values at median altitudes and the prediction of normal results. Am Rev Tuberc 79:457-467, 1959 ~ Sobol BJ, Park S, Emirgil C: Relative value of various spirometric tests in the early detection of chronic obstructive pulmonary disease. Am Rev Respir Dis 107:753-762, 1973
CHEST, 72: 1, JULY, 1977
9 Sobol BJ: Pulmonary function survey in Westchester County. Tubercology 23:6-12, 1965 10 Read J, Selby T: Tobacco smoking and ventilatory function of the lungs. Br Med J 2: ll04-ll08, 1961 ll Anderson DO, Ferris BG Jr: Role of tobacco in the causation of chronic respiratory disease. N Eng! J Med 267:787-794, 1962 12 Woolf CR, Suero JT: The respiratory effects of regular cigarette smoking in women. Am Rev Respir Dis 103:2637, 1971 13 Grimes CA, Hanes B: InHuence of cigarette smoking on the spirometric evaluation of employees of a large insurance company. Am Rev Respir Dis 108:273-282, 1973 14 Casier H: Accumulation of alcohol metabolites in the form of total lipids and fatty acids in the organism. Q J Stud Alcohol 23:529-548, 1962 15 Burch GE, DePasquale N: Alcoholic lung disease: An hypothesis. Am Heart J 73:147-148, 1966 16 Laurenzi G, Guarneri J, Carey J, et al: Bacterial clearance from the lungs of mice. Fed Proc 22:255, 1963 17 Green G, Kass E: Factors inHuencing the clearance of oacteria by the lung. J Clin Invest 43:769-776, 1964 18 Van Ganse WF, Ferris BG Jr, Cotes JE: Cigarette smoking and pulmonary diffusing capacity (transfer factor). Am Rev Respir Dis 105:30-41, 1972 19 Cotes JE, Field GB: Impairment of lung function after portacaval anastomosis. Lancet 1:952-955, 1968 20 RuH F, Hughes JMB, Stanley N, et al: Regional lung function in patients with hepatic cirrhosis. J Clin Invest 50:2403-2413, 1971 21 Stanley NN, Woodgate DJ: Mottled chest radiograph and gas transfer defect in chronic liver disease. Thorax 27:315-323, 1972 22 Daoud FS, Reeves JT, Schaefer JW: Failure of hypoxic pulmonary vasoconstriction in patients with liver cirrhosis. J Clin Invest 51:1076-1080, 1972
PULMONARY FUNCTION IN FORMER ALCOHOliCS 51
Pulmonary function was evaluated in 44 former alcoholics (abstinence, 0.5 to 32 years) without cardiac or specific pulmonary disease. All were members of Alcoholics Anonymous. Fourteen subjects (32 percent) were nonsmokers, ex-smokers, and cigar or pipe smokers, yet 28 subjects (64 percent) bad abnormal expiratory flow rates, and 17 (39 percent) bad an elevated value for the ratio of the residual volume to the total lung capacity. Single-breath diffusing capacity was abnormal in seven subjects (16 percent). Of interest was the bigb incidence
The common clinical impression that there is a high prevalence of nonspecific pulmonary disease among chronic alcoholics has recently been confirmed. 1.2 The characteristic functional abnormalities are airway obstruction and impainnent of diffusion, both of which are almost universally present. In contradiction to the generally held view, these abnormalities in function cannot be explained on the basis of cigarette smoking and frequent pulmonary infections. On the contrary, these studies suggested that functional abnormalities, at least in part, might be caused by alcohol per se. It was also shown that short periods ( ie, up to three weeks) of abstinence had no significant effect on the observed abnormalities; t.2 however, it is not known whether the deleterious effects of excessive ingestion of alcohol are permanent, regress, or disappear entirely with long periods of abstinence. A knowledge of the pulmonary function of former alcoholics could shed light on the relationship between chronic alcoholism and chronic pulmonary disease. This study presents data on former alcoholics and compares their pulmonary function with that of alcoholic patients previously studied and reported.2 °From the Cardiopulmonary Laboratory, Westchester County Medical Center ( Grasslands Hospital), and the Department of Medicine, New York Medical College, Valhalla, NY. Presented in part at the NCA-AMSA Medical/Scientific Meeting in Washington, D.C., May 6-8, 1976. With the assistance of Ms. Lyrmea Van Voorhies, Ms. Kathleen Palmer, and Ms. Deborah Pomier. Supported in part by the Westchester Heart Association. • • Associate Professor of Medicine. tProfessor of Medicine. Manuscript received June 11; revision accepted October 1. Reprint requests: Dr. Emirgil, Pulmo!liJ!JI Lizboratory, Westchester Count11 Medical Center, Valhalla, New York 10595
CHEST, 72: 1, JUlY, 1977
(17 percent) of obstructive phenomena among the women. This bigb incidence of abnormalities among both the men and women could not be attributed to previous pulmonary infection or smoking. Comparison of these patients with chronic alcoholics suaests that the obstructive component In these patients is, in part, a result of their past alcoboHc Intake and that it is not reversed by abstinence. On the other band, the impairment in diffusion, which was so common In alcoholics, appears to be reversible with sobriety.
MATERIAI.S AND METHODs
The subjects were chosen from members of Alcoholics Anonymous. This appeared to be the best way of assuring sobriety. Three local chapters with a sufficiently large membership ( 124 people) were chosen. The 103 members present at the chapter meetings were given a letter explaining the study and asking them to fill out a questionnaire. They were asked to return the questionnaire whether or not they were willing to participate in the study. To be included in the study, all subjects had to have imbibed excessively for eight years or longer, followed by a period of abstinence of six months or longer. They had to be willing to have a physical examination, chest x-ray film, and electrocardiogram, to perform tests of pulmonary function, and to permit a venipuncture. A minimum of eight years of chronic alcoholism was used as a criterion with the hope that the subjects in the present study would be comparable with the chronic alcoholics in the previous study with respect to consumption of alcohoJ.2 Eighty-four ( 82 percent) of the members responded. Of these, seven ( 8 percent) refused to participate in the study, and 20 ( 24 percent) did not meet the criteria. The remaining 57 subjects met the criteria and were willing to participate. Tiley were paid to compensate for their time and inconvenience, and all signed an informed consent. The study extended over a period of three months. After all of the data were obtained, 13 subjects were excluded for the following reasons: one had bronchial asthma; two had anabnormalECG; one had a slightly enlarged heart; three had pulmonary lesions on the chest x-ray film; and six had a history of drug addiction. The remaining 44 subjects without cardiac or specific puhnonary disease (tuberculosis, bronchiectasis, sarcoidosis, etc) formed the basis of this study. None of these subjects had been studied before or included in the previous study.2 The form used for the medical history was the standard British Medical Research Council Questionnaire. In addition, a detailed history of alcohol ingestion was obtained from all subjects. In order to compare the different types of alcohol, beer was considered to contain 4 percent alcohol, wine 12 percent, and hard liquors 45 percent. In this study,
PULMONARY FUNCnON IN FORMER ALCOHOLICS 45
the term, "pint," then refers to 16 oz of hard liquor, 60 oz of wine, and 180 oz of beer. Habits of smoking and drinking were recorded in terms of duration and daily consumption, and each was converted to pack-years or pintyears. Smokers who stopped smoking at least six months ·prior to the study were classified as ex-smokers. A sample of venous blood was obtained from every subject for automated analysis (SMA-12) of blood chemistry ( levels of calcium, glucose, inorganic phosphate, creatinine, uric acid, cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, lactic dehydrogenase, and serum glutamic-oxaloacetic transaminase); for a hematocrit reading, and for determinations of At-antitrypsin level. The serum level of At-antitrypsin was determined by radial immunodiffusion, with reagents obtained from a commercial supplier ( Behring Diagnostics). The chest x-ray film and ECG were interpreted by a roentgenologist and cardiologist who did not know the subjects or the results of the studies of pulmonary function. Spirometric studies were performed on a waterless spirometer (Jones Pulmonor) with the subject in the sitting position. The expiratory curves were analyzed for vital capacity ( VC), forced vital capacity ( FVC), the forced expiratory volume in one second ( FEV t ) , the ratio of FEV JIFVC, and the mean forced expiratory flow during the middle half of the FVC ( FEF25-75$). The highest value of three or four determinations was used. The functional residual capacity ( FRC) and the airway resistance ( Raw) were measured by body plethysmographic studies, as previously describedS and subsequently modified.• Specific conductance (Gaw/VL) was determined at the lung volume at which Raw was measured. The expiratory reserve volume ( ERV) was determined by spirometric studies. This value, together with the VC and FRC, permitted the calculation of total lung capacity ( TLC), residual volume ( RV), and the ratio of RV/TLC. The single-breath diffusing capacity for carbon monoxide ( Dsb) was determined by the method of Ogilvie and co-workers.' The predicted values for RV, TLC, and RV/TLC for male subjects were obtained from Boren et al. • These values for RV and TLC for female subjects were obtained from Goldman and Becklake. 7 The normal value for RV/TLC for female subjects was assumed to be the same as for male subjects. Normal values for Dsb were obtained from studies of 114 male and 58 female healthy subjects. Smokers and ex-smokers were not excluded (the study was done by Abraham S. Kuperman, M.D., at the Albert Einstein College of Medicine, Bronx, NY). Predicted values for Dsb were calculated from the following two formulas (where height was expressed in centimeters) : ( 1 ) for patients less than 35 years of age, Dsb =Heigh~ X 6/10' ± 6.6; and ( 2) for patients more than 34 years of age, Dsb =Heigh~ (804- 6 Age)/10S ± 6.6. The predicted values and limits of normal for the VC, FEVt, FEV1/FVC, and FEF25-75$ were determined by criteria previously published.• In all instances the standard error of the estimate (SEE) was multiplied by 1.64 and added to or subtracted from the predicted value. A common method of determining the limits of normal is to use the predicted value ± 2 SEE. This eliminates 5 percent of the normal population, ie, 2.5 percent from both the upper and lower tail of the normal distribution curve; however, in tests of ventilatory funCtion, abnormality exists only at one end of the distribution curve. Therefore, to eliminate 5 percent from this end, 1.64 SEE is used. • The statistical significance of observed diHerences was determined by the use of the
48 EMIRGIL, SOBOL
Student's t-test. A value for probability of less than 0.05 was considered significant. REsULTS
The clinical data are given in the following tabulation, showing the numbers of subjects (numbers within parentheses are percentages) : Total subjects
44
Sex Male Female
25 (57) I9 (43)
Smoking Cigarette Cigar Pipe Ex-smoker Nonsmoker
30 (68) I (2) I (2)
8 (18) 4 (9)
Chronic bronchitis (clinical)
IS (4I)
Total subjects with symptoms
26 (59)
The percentage of subjects by sex in our sample approximated the percentage in the three chapters of Alcoholics Anonymous. Fourteen ( 32 percent) of the subjects were nonsmokers, ex-smokers, or pipe and cigar smokers. Eleven subjects ( 25 percent) had a palpable liver (one to two fingerbreadths). With the exception of slightly elevated concentrations of ·alkaline phosphatase in 16 subjects, the results of automated studies (SMA-12) of blood chemistry were within the limits of normal; however, there was no relationship between the elevated concentration of alkaline phosphatase and a palpable liver. The serum level of at-antitrypsin was normal in all but one subject. This person was a heterozygote and had normal pulmonary function. The mean hematocrit reading was 43 ± 4 percent, and values ranged from 36 to 49 percent. Twentysix subjects (59 percent) had respiratory symptoms, and 18 ( 41 percent) had chronic bronchitis based on the standard British Medical Research Council Questionnaire. Dyspnea was the only symptom in eight subjects. Thirteen subjects ( 30 percent) gave a history of having 18 episodes ( 1.3 episodes per subject) of acute bronchitis or pneumonia or both. During the past three years, only one subject had one episode of pneumonia, and one subject had one episode of acute bronchitis. Additional clinical data and the results of studies of pulmonary function are listed in Table 1. The Cigarette smoking, drinking habits, age, and duration of sobriety varied very substantially. During the period of sobriety, seven subjects increased, ten decreased, and 12 did not change their consumption of cigarettes. There was a very slight decrease in the total consumption of the 30 current smokers.
CHEST, 72: 1, JULY, 1977
Table l-Pulmonary Function and CUnical Data from 44 Former Akolaoliu
Measurement
Table 2--Dala from 13 Female Former Akolaolic Smolcer•
No. with Abnormal Results Mean±SD Range (percent)
Age, yr
47±9
32-71
Alcohol Pint-years• Duration of consumption, yr
28±15 22±9
7-66 9-43
Measurement
No. with Abnormal Results Mean±SD Range (percent)
Age, yr
47±9
34-67
VC, percent of predicted
96±13
82-125
0
FEV., percent of predicted
89±16
67-130
3 (23)
FEV./FVC, percent
75±6
~
6 (46)
FEF25-75%, percent of predicted
58±26
30-116
10 (77)
Dab, percent of predicted
85±13
~112
2 (15)
RV /TLC, percent of predicted 145±26
96-195
7 (54)
Smoking•• Pack-years Duration, yr
39±20 28±11
5-82 9-43
Sobriety, yr
5.7±6.3
0.5-32
VC, percent of predicted
97±13
71-125
2 (5)
FEV., percent of predicted
86±20
34-130
13 (30)
Smoking, pack-years
33±19
5-77
FEV./FVC, percent
72±12
32-88
23 (52)
Consumption of alcohol, pint-years•
16±9
6-36
Sobriety, mo
52±36
8-108
FEF25-75%, percent of predicted Gaw/VL, L/sec/cm H,O/Lt TLC, percent of predicted
59±26
8-116 28 (64)
0.20 ±0.13 0.04-0.53 14 (32) 102±12
81-145
2 (5)
RV /TLC, percent of predicted 130±32
75-230
17 (39)
Dab, percent of predicted
51-135
7 (16)
92±21
*See "Materials and Methods" for definition of pint-years.
••as subjects (current cigarette smokers and ex-smokers). tNormal value,
> 0.16.
During the first year of sobriety, nine subjects stopped smoking cigarettes completely. Of these, eight were classified as ex-smokers. The average abstinence from smoking was three years, and the duration varied from six months to ten years. There was no significant difference between the ex-smokers and smokers with respect to cigarette consumption ( P > 0.3) and expiratory flow rates ( P > 0.5). Therefore, ex-smokers were not analyzed as a separate group. Only two patients had an abnormal VC. These two patients had a normal TLC, severely impaired flow rates, and abnormally elevated RV /TLC, indicating that the reduced VC was not due to restrictive pulmonary disease. Using the FEF25-75% as the criterion, 28 subjects ( 64 percent) had chronic obstructive pulmonary disease. The incidence of an abnormal value for FEF25-75% was 70 percent ( 21 subjects) in the current smokers, 75 percent (three subjects) in nonsmokers, and 50 percent (four subjects) in ex-smokers. The subject who was a cigar smoker had moderate chronic obstructive pulmonary disease. The pulmonary function of the pipe smoker was normal. The FEVt!FVC was abnormal in 23 patients (52 percent) and was always associated with an abnormal FEF25-75%. The deCHEST, 72: 1, JULY, 1977
*See "Materials and Methods" for definition of pint-years.
gree of obstruction varied from mild to severe. More than one-third of the subjects ( 39 percent or 17 subjects) had abnormally elevated RV /TLC, and with one exception an abnormal RV /TLC was always associated with an abnormal FEF25-75%. Only seven subjects ( 16 percent) had an abnormal Dsb. No patient had an abnormally low TLC. The pulmonary function and clinical data on female former alcoholic smokers are summarized in Table 2. The FEF25-75'1, was abnormal in ten subjects (77 percent). Using the FEVt!FVC as the criterion, six subjects ( 46 percent) had chronic obstructive pulmonary disease. More than half (54 percent or seven) of these 13 subjects with impaired flow rates also had abnormally elevated values for RV/TLC. Table 3---Data from Female Former Akolaolic Non.molcen
Measurement
Case 1 Case 2 Case 3 Case 4
Age (yr), Sex
49, F 44, F 43, F 41, F
VC, percent of predicted
107
108
105
122
FEV1 /FVC, percent
68*
66*
80
80
FEF25-75 %, percent of predicted
55*
35*
65*
72
91
116
95
101
Dab, percent of predicted
111
RV /TLC, percent of predicted
145* 153*
117
Consumption of alcohol, pint-years••
11
28
13
27
Sobriety, mo
24
25
19
49
*Beyond the limits of normal. ••See "Materials and Methods" for definition of pint-years.
PULMONARY FUNCnON IN FORMER ALCOHOLICS 47
The clinical and pulmonary function data on the subjects who never smoked are shown in Table 3. This group consisted of four middle-aged women. The FEF25-75~ was abnormal in three subjects and the FEVt!FVC and RV/TLC in two subjects. DISCUSSION
The high prevalence of obstructive pulmonary disease and the low prevalence of an abnormal diffusing capacity in these former alcoholics is interesting and surprising. The results of the present study show that two common abnormalities of chronic alcoholics (namely, obstructive pulmonary disease and impaired diffusion) were affected differently by sobriety. It appears that abstinence from alcohol restored diffusion to normal but caused no improvement in the obstructive phenomenon. To determine to what extent previous alcohol Consumption is a contributing factor to the high prevalence of obstructive pulmonary disease, an attempt must be made to separate the effects of previous pulmonary infections and cigarette smoking from the effects of alcohol per se. In the present study the frequency of past chest illnesses per subject ( 1.3 episodes per person) did not differ significantly from that of an apparently healthy population. 2.11 Furthermore, all but two subjects had their chest illnesses many years prior to the present study. It has been shown that 1.3 episodes of past chest illness per person do not impair pulmonary function. 2•9 Therefore, it is reasonable to assume that past pulmonary infections are not the cause of abnormal function in these former alcoholics. Fourteen ( 32 percent) of the subjects were exsmokers, nonsmokers, and pipe or cigar smokers, yet the incidence of obstructive pulmonary disease was 64 percent ( 28 subjects). There were 30 current cigarette smokers. Of these, 21 ( 70 percent) had an abnormal FEF25-75~, and 16 (53 percent) had an abnormal FEVt!FVC. Although the role of cigarette smoking in the pathogenesis of obstructive pulmonary disease is well established, this high prevalence is difficult to explain on the basis of smoking alone. In the present study, male current cigarette smokers as a group can be classified as moderate to heavy smokers (average lifetime smoking of 14,000 packages). The FEF25-75~ was abnormal in 11 subjects (65 percent), and the FEVt!FVC was abnormal in ten (59 percent). The percentage of abnormal ventilatory function has been reported as being 25 percent in male moderate smokers 10 and 30 percent in male very heavy smokers (lifetime smoking of more than 18,000 packages) .11 An attempt was made to correlate pulmonary 48 EMIRGIL, SOBOL
function with smoking and alcoholic intake. Only expiratory flow rates correlated with the consumption of both cigarettes and alcohol; however, the correlations were too poor ( r < 0.4) to be meaningful. These poor correlations might be due to the fact that former alcoholics formed a nonhomogeneous group. There was no correlation between the consumption of alcohol and that of cigarettes. The duration and intake of alcohol did not correlate with the duration of sobriety. Sobriety was not related to smoking habits following the onset of abstinence; some subjects discontinued smoking, while others decreased or even increased their consumption of cigarettes. Although it would have been desirable to divide the subjects into groups with comparable exposure to alcohol and cigarette smoke and comparable duration of abstinence, this was not possible. No group of subjects was sufficiently large to make a valid comparison with another group with a different profile for consumption of alcohol and cigarettes and for abstinence. More than three-fourths ( 77 percent or ten) of the female smokers had abnormal expiratory flow rates. This was an unexpected finding. Although published reports show a statistically significant difference between the ventilatory function of female nonsmokers and heavy smokers, the magnitude of this difference is minor, and only a small percentage of female heavy smokers have abnormal flow rates. 12.1 3 An even more striking observation was the presence of chronic obstructive pulmonary disease in three out of four women who never smoked. The very high incidence of abnormal flow rates among female former alcoholics suggests that past
alcoholism must have played a role in the pathogenesis of their obstructive pulmonary disease. In addition, the equations of Grimes and Hanes 13 were used to correct the FEV1 and FEF25-75~ for smoking. Despite this correction, the FEV1 in 26 smokers ( 87 percent) and the FEF25-75~ in 25 smokers ( 83 percent) were less than predicted (Table 4). The difference between the observed and predicted values (corrected for smoking) was highly significant. Both the FEV1 and FEF25-75~ were abnormally low (predicted values-1.64 X SEE) in 14 subjects ( 47 percent) (Table 4). Although in a population of cigarette smokers, the effects of other toxic agents cannot be separated with certainty from the effects .of cigarette smoking, these observations suggest that smoking alone cannot account for the high prevalence of obstructive pulmonary disease among former alcoholics. To determine the role of alcohol in the pathogenesis of pulmonary disease in alcoholics, it is necessary to make comparisons between the functional CHEST, 72: 1, JULY, 1977
Table 4--Data on FEJ' 1 and FEF25-75% in 30 Current Ci«arelle Smolcer•
Measurement No. of subjects
Men
Women
17
13
FEV1 Observed, L (mean ± SD) 3.1 ±0.9 Predicted, L (mean ± SD)* 3.7±0.5 P value for observed vs predicted 0.005 No. with values less than predicted (percent)* 14 (82) 7 (41) No. with abnormal results (percent) FEF25-75% Observed, L (mean ± SD) 2.4±1.1 Predicted, L (mean ± SD)* 3.5±0.7 P value for observed vs predicted 0.001 No. with values less than predicted (percent) • 13 (76) No. with abnormal results (percent) 8 (47)
2.1 ±0.4 2.6±0.3 0.001 12 (92) 7 (54) 1.8±0.9 2.9±0.4 0.001 12 (92) 6 (46)
*Corrected for smoking.
abnormalities of alcoholics and former alcoholics. It will also be necessary to discuss briefly the effects of cirrhosis of the liver on pulmonary function, since chronic hepatic disease is known to alter a number of respiratory functions. To facilitate comparisons between alcoholics and former alcoholics, pertinent data from the previous study of alcoholics2 and the present study were summarized in Table 5. The mean age of the former alcoholics is slightly but significantly higher than that of the alcoholics; however, this difference in age has no effect on function, since pulmonary function is corrected for age. There· is no significant difference between alcoholics and former alcoholics with respect to consumption of alcohol ( P > 0.3) and cigarettes ( P > 0.6). The hematocrit readings were also listed, since the level of hemoglobin in the pulmonary capillaries affects diffusion. The hematocrit readings of two groups did not differ significantly ( P > 0.5). Therefore, both groups are similar with respect to consumption of alcohol and cigarettes imd with respect to the hematocrit reading. It can be seen from Table 5 that the common functional abnormality of alcoholics (namely, obstructive pulmonary disease) does not appear to be reversible with abstinence. As a group, there was no significant difference between alcoholics2 and former alcoholics with respect to the expiratory flow rates. Although the high incidence of chronic pulmonary disease in alcoholics is well accepted and recently documented, 1.2 little information exists with regard to the effects of alcohol on the lungs. Experimental studies in animals have shown that metabolites of alcohol accumulate in the lungs 14 and that intraperitoneally injected alcohol can produce histochemical alterations in the pulmonary tissue.15 It
CHEST, 72: 1, JUlY, 1977
has also been shown that alcohol reduces the clearance of inhaled bacteria from the lungs. 16.1 7 In alcoholics, a considerable amount of alcohol can reach the lungs without being metabolized by the liver, and this may produce a direct toxic effect on the lungs. Although there is no experimental evidence, metabolites of alcohol may also accumulate in the human lungs; however, the effects of alcohol metabolites on the lung is not known. Impaired clearance of bacteria from the lungs may make alcoholics more susceptible to chronic bronchial infections. It is conceivable that if the combined effect of alcohol and its metabolites and the depressed bacterial clearance can cause injury to pulmonary tissue, they might also make the lungs more susceptible to the injurious effects of cigarette smoking or other toxic agents. It is possible that once a certain degree of pulmonary injury takes place, function may not be restored to normal in spite of abstinence from consumption of alcohol. Table 5--Compariwm behCJeen Aleolaoliu* arul Former Aleolaolie•
Measurement
No. with Abnormal Results Mean±SD Range (percent)
Age, yr Alcoholics Former alcoholics
40±9** 47±9**
26-57 32-71
Consumption of alcohol, pint-yearst Alcoholics Former alcoholics
36±20t 28±15t
10-89 7-66
Smoking, pack-years Alcoholics Former alcoholics
42±25t 39±20t
14-101 5-82
Hematocrit reading, percent Alcoholics Former alcoholics
42±4t 43±4t
36-47 36-49
FEV./FVC, percent Alcoholics Former alcoholics
72±8t 72±12t
58-83 32-88
FEF25-75%, percent of predicted Alcoholics Former alcoholics
58±26t 59±26t
26-106 16 (70) 8-116 28 (64)
Dsb, percent of predicted Alcoholics Former alcoholics
66±16§ 92±21§
13 (57) 23 (52)
.. 39-104 51-135
14 (61) 7 (16)
*Data on alcoholics from Emirgil et al. 2 Number of alcoholics was 23 (four female and 19 male subjects); one was a nonsmoker, and 22 were cigarette smokers. **P = 0.005. tSee "Materials and Methods" for definition of pint-years. tNot significant. §P - 0.001.
PULMONARY FUNCTION IN FORMER ALCOHOLICS 49
The other common and puzzling abnormality of alcoholics is the unexplained impairment of diffusion.1.2 This abnormality appears to be reversible with abstinence (Table 5). In the previous study, 61 percent ( 14) of 23 chronic alcoholics had an abnormal Dsb. 2 This high incidence could not be attributed to anemia or cigarette smoking. None of the alcoholics had significant anemia, and even after a correction for smoking 18 was made, 40 percent (nine) of the patients remained with an abnormal Dsb. 2 These results are similar to those of Banner. 1 In the present study, only seven ex-alcoholics ( 16 percent) had an abnormal Dsb. There is a significant ( P < 0.001) and substantial difference between the mean percentage of the predicted value for Dsb of alcoholics ( 66 -+- 16 percent) and that of former alcoholics ( 92 ± 21 percent). This difference is not due to a difference in the smoking and drinking habits or the level of hemoglobin of the two populations. In addition, in both studies the same method for determining Dsb and the same equipment, prediction equations, and criteria of abnormality were used, and the same technician performed the test; however, there was one important difference between the two groups. The majority of chronic alcoholics had clinical and laboratory evidence of significant hepatic disease. In the present study, only a small percentage of the former alcoholics might have had mild hepatic disease. There are two possible explanations for the difference in Dsb: ( 1) Alcohol has a direct toxic effect on the lung and produces anatomic or physiologic changes, or both, which interfere with the process of diffusion; these changes are reversible, and abstinence from alcohol restores gas exchange to normal. ( 2) The impaired diffusion is secondary to alcoholic hepatic disease which, through some unknown mechanism, impairs gas exchange; abstinence from alcohol restores hepatic function to normal, and diffusion becomes normal. There are data in the literature to support both hypotheses. Accumulation of alcohol metabolites in the lungs 14 and histochemical changes in the pulmonary tissue secondary to intraperitoneal injection of alcohoP1 support the first hypothesis; however, the bulk of published work supports the second hypothesis. The occurrence of reduced diffusion in patients with cirrhosis of the liver has been well documented. 19-21 The impaired diffusion is not related to the etiology of the hepatic disease and can occur not only in patients with alcoholic hepatic disease but also in those with primary biliary cirrhosis and active chronic hepatic disease. 19-21 These observations strongly suggest that impaired diffusion is related to hepatic dysfunction. It has been postu50 EMIRGIL, SOBOL
lated that the combined effect of several abnormalities, such as increased capillary permeability, reduced colloidal osmotic pressure due to decreased plasma levels of albumin, and hormonal changes, in patients with hepatic disease can cause interstitial pulmonary edema, which may interfere with the process of diffusion. 2.2o It has also been suggested that the impaired diffusion may be the reflection of some pattern of pulmonary inhomogeneity. 19 Recent work has shown that regional abnormalities of ventilation and perfusion can occur in patients with cirrhosis of the liver; 20.22 however, the cause of the impairment of diffusion in chronic hepatic disease remains uncertain. Although in the present study, no subject could be diagnosed as having cirrhosis of the liver, some of them might have had mild alcoholic chronic hepatic disease, since 11 subjects had a palpable liver, and 16 had a slightly elevated concentration of alkaline phosphatase. Of the seven subjects who had abnormal diffusion, only two had a palpable liver. Of these, one had minimal obstructive pulmonary disease, and in the second, impaired diffusion was the only abnormality. It is possible that in these two subjects, impaired diffusion was secondary to hepatic disease. The remaining five subjects with abnormal diffusion had functional and roentgenographic evidence of moderate to severe pulmonary emphysema. These findings indicate that in the absence of hepatic disease, the impaired diffusion of former alcoholics is the result of pulmonary emphysema. There is one important consideration that should be mentioned. Although alcoholics and former alcoholics as a group were similar in important respects ( ie, consumption of cigarettes and alcohol and the hematocrit reading), the two groups might have been different in other characteristics. Therefore, comparisons between the two groups have limitations. The effect of sobriety for a given individual patient cannot be determined from these comparisons, since the pulmonary function of the subjects in the present study was not evaluated while they were alcoholics. It is possible that the impaired function of certain individuals may improve or be restored to normal with abstinence. It is also possible that once a certain degree of pulmonary injury takes place, the abnormal function of some alcoholics may progressively deteriorate, in spite of sobriety. In conclusion, the data show that former alcoholics have a high incidence of obstructive pulmonary disease, usually associated with an abnormally elevated RV /TLC and occasionally with an impaired Dsb. This high incidence suggests that obCHEST, 72: 1, JULY, 1977
structive pulmonary disease of former alcoholics is, in part, a result of their previous chronic alcoholism. ACKNOWLEDGMENT: We are indebted to Ms. Philomena Adinaro, Ms. Pattie Baskette, Ms. Catherine Doyle, Ms. Kathleen Kaplan, Ms. Sandra Kaplan, Ms. Trudy Singer, and Ms. Deborah Telesco.
1 Banner AS: Pulmonary function in chronic alcoholism.
Am Rev Respir Dis 108:851-857, 1973 2 Emirgil C, Sobol BJ, Heyman B, et al: Pulmonary function in alcoholics. Am J Med 57:69-77, 1974 3 DuBois A, Botelho S, Cornroe J: A new method for measuring airway resistance in men using a body plethysmograph: Values in normal subjects and in patients with respiratory disease. J Clin Invest 35:327-335, 1956 4 Sobol BJ: Methods for simplifying constant volume body plethysmograph. J Appl Physiol 27:259, 1969 1) Ogilvie C, Forster R, Blakemore W, et al: A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest 36:1-17, 1957 ~ Boren H, Kory R, Syner J: The Veterans Administration-Army cooperative study of pulmonary function: 2. The lung volume and its subdivisions in normal men. Am J Med 41:96-114, 1966 7 Goldman HI, Becklake MR: Respiratory function tests: Normal values at median altitudes and the prediction of normal results. Am Rev Tuberc 79:457-467, 1959 ~ Sobol BJ, Park S, Emirgil C: Relative value of various spirometric tests in the early detection of chronic obstructive pulmonary disease. Am Rev Respir Dis 107:753-762, 1973
CHEST, 72: 1, JULY, 1977
9 Sobol BJ: Pulmonary function survey in Westchester County. Tubercology 23:6-12, 1965 10 Read J, Selby T: Tobacco smoking and ventilatory function of the lungs. Br Med J 2: ll04-ll08, 1961 ll Anderson DO, Ferris BG Jr: Role of tobacco in the causation of chronic respiratory disease. N Eng! J Med 267:787-794, 1962 12 Woolf CR, Suero JT: The respiratory effects of regular cigarette smoking in women. Am Rev Respir Dis 103:2637, 1971 13 Grimes CA, Hanes B: InHuence of cigarette smoking on the spirometric evaluation of employees of a large insurance company. Am Rev Respir Dis 108:273-282, 1973 14 Casier H: Accumulation of alcohol metabolites in the form of total lipids and fatty acids in the organism. Q J Stud Alcohol 23:529-548, 1962 15 Burch GE, DePasquale N: Alcoholic lung disease: An hypothesis. Am Heart J 73:147-148, 1966 16 Laurenzi G, Guarneri J, Carey J, et al: Bacterial clearance from the lungs of mice. Fed Proc 22:255, 1963 17 Green G, Kass E: Factors inHuencing the clearance of oacteria by the lung. J Clin Invest 43:769-776, 1964 18 Van Ganse WF, Ferris BG Jr, Cotes JE: Cigarette smoking and pulmonary diffusing capacity (transfer factor). Am Rev Respir Dis 105:30-41, 1972 19 Cotes JE, Field GB: Impairment of lung function after portacaval anastomosis. Lancet 1:952-955, 1968 20 RuH F, Hughes JMB, Stanley N, et al: Regional lung function in patients with hepatic cirrhosis. J Clin Invest 50:2403-2413, 1971 21 Stanley NN, Woodgate DJ: Mottled chest radiograph and gas transfer defect in chronic liver disease. Thorax 27:315-323, 1972 22 Daoud FS, Reeves JT, Schaefer JW: Failure of hypoxic pulmonary vasoconstriction in patients with liver cirrhosis. J Clin Invest 51:1076-1080, 1972
PULMONARY FUNCTION IN FORMER ALCOHOliCS 51