Document vVYJ2gNO77oVJLoB46bo97E8Z

J. W. U)eU</ Airway Disease in Non-Smoking Asbestos Wbrkers KAYE H. KILBURN, M.D. RAPHAEL H. WARSHAW KENNETH EINSTEIN, M.D.* JONINE BERNSTEIN, M.A.* USC Laboratory for Environmental Sciences USC School of Medicine 2025 Zonal Avenue Los Angeles, California ABSTRACT. Ninety-seven non-cigarette-smoking white male insulators from the midwestem United States had significantly reduced forced expiratory volume in 1 second (FEV,,) (P < .0017) and forced expiratory flow from 75 to 85% of expired volume (FEF7S^,) (P < .042) when compared to a reference population of Michigan male nonsmokers. There were parenchymal opacities with a profusion of 1/0 or greater in 7 and pleural changes in 13 of these 97 nonsmokers. Asbestos, in the absence of cigarette smoke effects and other diseases, appears to decrease airflow, probably by the distortion of small airways (< 2mm) by peri bronchiolar fibrosis. This stiffening of the lung parenchyma protects midflow <FEFIS_7S) as the fibrosis increases the lung's radial traction on airways larger than 2 mm. This observation contributes to the natural history of physiological impairment due to asbestos disease. IT IS generally agreed that severe asbestosis reduces lung volume and that it reduces air flow only late in the course of the disease. This picture of asbestosis is derived from studies in which 75% to over 90% of workers studied had smoked cigarettes. Too few nonsmokers have been available to examine the effect on pulmo nary function of asbestos alone. Reductions in air flow as measured by the forced expiratory volume in one second (FEV, 0) have been regarded as a late sequelae of severe loss of volume or as reflecting the effects of cigarette smoking or of chronic bronchitis due to in dustrial or other exposures. Recently, attention has been focused on the earlier diagnosis of asbestosis, par ticularly its detection by radiography of the chest * Or. Einstein and (onine Bernstein are currently at Tufts University Medical Center and Ml. Sinai School of Medicine, respectively. employing the pneumoconiosis criteria of the Interna tional Labor Organization (ILO).1 Screening programs have provided opportunities to detect and study early disease associated with asbestos exposure. One of the questions is whether asbestosis produces physiological abnormalities of the lung prior to its causing disease which is radiographically detectable. The second ques tion is whether the airways are primarily involved early in asbestos disease. The latter issue is important in ap portioning causal responsibility for impairment be tween asbestos exposure and cigarette smoking. This study examines the degree to which the airways obstruction, particularly small airways obstruction, was present in non-cigarette-smoking workers who were ex posed to asbestos as insulators. It also uses smoking-spe cific comparisons and predicted values, to subtract the effect of smoking to determine whether smoker's pulmo nary functions show additive or even synergistic effects. November/December 1985 [Vbl. 40, (No. 6)| 293 I I < \' < METHODS We studied 416 white asbestos insulators from six midwestern cities: Cleveland, Akron, Dayton and Youngs town, Ohio; Detroit, Michigan; and South Bend, In diana. Ninety-seven subjects had never smoked ciga rettes, 172 were ex-cigarette smokers, and 147 were cur rent smokers. The nonsmokers were analyzed in detail for evidence of airway obstruction unconfounded by the effects of cigarette smoking. Ages of the nonsmokers ranged from 19 to 69 yr, with a mean age of 40.0 yr. They were actively employed at the time of study. We administered a respiratory questionnaire derived from the Medical Research Council bronchitis question naire with additional questions on asthma and on occu pational exposures. It defined the time of initial asbes tos exposure, duration and intensity of exposure, and exposure to other dusts, fumes, and aerosols. Chest radiographs were standard posteroanterior 14' x 17' films taken at a 6-ft distance at full inspiration and were read for asbestosis according to the ILO classification1 by an American College of Radiology-certified "B" reader. Spirometry was performed using methods and equipment which met the American Thoracic Society criteria.2 Reference values were those of Miller et al.J Thus, the insulator's spirometric values were compared with those of geographical controls obtained in a crosssectional study of a stratified random sample of Michi gan and expressed as percent predicted. The compari sons were made to all white male Michigan subjects in each smoking category, including those with cough and sputum, not just to normal subjects. RESULTS The mean values for age, height, forced vital capacity (FVC), FEV, 0, forced expiratory flow from 25 to 75 per cent of expired volume (FEF25_75), and forced expiratory flow from 75 to 85 percent of expired volume (FEF75.85), together with percent predicted are shown in Table 1. In asbestos-exposed nonsmokers, FEF7S^5 and FEV,,, were reduced. The current smokers showed lower val ues despite being compared to smokers as did the ex smokers whose values were lowest. The composite flow-volume diagram in Figure 1 shows the reduction in terminal flow and in FEV, 0 with an apparent increase in midflow, FEF2S_75. Fig. 1. Dished line represents a composite flow volume curve for non smoking asbestos workers. Solid line is a normal flow volume curve. F75-k is decreased but FEFjj.^ is increased in these workers. Table 2.--Age and Height Adjusted Differences in Nonsmokers Insulators Minus Reference Population of Michigan Men FVC vl0 Log FEFJWS Log flfjS-K Adjusted Difference Standard Error of Difference -0.124 -0.221 0.061 -0.101 0.084 0.070 0.039 0.049 P 0.1400 0.0017 0.1170 0.0420 The age- and height-adjusted differences of the spiro metric indices (asbestos workers minus Michigan) for nonsmokers are presented in T ble 2. Values for the in sulators were significantly smaller than those for the Michigan population's nonsmokers in FEV, ,, and in log FEF7S^. In modelling the Michigan comparison group Table 1.--Mean Values and Percentage Predicted for Midwestern Insulators as Compared to Michigan Men Variable Number Age Height FVC (L) FEV, 0 (L) FEF2s_75 (L/sec) fef75-ss (Vsec) Nonsmokers Observed (111 Predicted) Ex-smokers Observed (% Predicted) Current Smokers Observed (% Predicted) 97 40.0 69.3 4.90 3.81 4.09 1.08 (97.7) (92.4) (105.4) (92.4) 172 44.0 69.0 4.45 3.27 3.10 0.77 (90.5) (86.7) (96.7) (74.5) 147 48.2 69.1 4.47 3.38 3.28 0.73 (92.5) (90.5) (101.6) (81.5) 294 Archives of Environmental Health 10003220 I 0 log FEF-S_,,S and log FEF,, .7, were related linearly to age and height just as FVC and FEVI0 were direct linear functions of age and height. There were parenchymal ir regular opacities with a profusion of 1/0 or greater in 7 and pleural changes in 13 of the 97 nonsmokers. The only measure we had of exposure intensity was self-re ported by questionnaire, and it was not predictive of either radiographic or spirometric abnormality. Twentyone of the 97 nonsmokers (21.6%) had a history of chronic bronchitis. As a group, asbestos-exposed nonsmoking insulators had significantly lower (P < .042) terminal airflows as indicated by FEF75_85 than a comparison population from the same geographic area. FEV, ,, was significantly lower (P < .0017) for the insulators as well, and was 92.4% of the percent predicted. Although the mid-flows in this group were slightly greater than those of the con trols, the FVC was smaller by 0.124 L. These differences were not statistically significant. The decreases in FEF7S^S and FEV, ,, in current smokers and ex-smokers exceeded those in nonsmokers because these were smoking-spe cific comparisons. Thus, subtraction of smoking effect revealed that smokers exposed to asbestos still had greater average decreases than nonsmokers. past, i.e., up to 85%, it has been difficult to compile suf ficient data on litolong nonsinokers exposed to asbes tos to examine the effects of asbestos alone on airways This study adds to the evidence that asbestos alone produces a small airway lesion which not only can be seen pathologically as was observed 50 years ago by Gloyne,4 but can be measured physiologically. Further studies of larger numbers of insulators covering a broader array of physiologic changes, an increased profusion of irregular opacities, and perhaps, examin ing those with asbestos pleural thickening and plaques are needed to resolve the stages of physiological im pairment as asbestosis progresses. The natural history of asbestosis resulting from the exposure levels of the last two decades, of which this study contributes, re mains to be completed. Submitted for publication March 24. 1985; accepted lor publication April 15. 1985. Requests for reprints should be sent to: Kaye H. Kilburn. M.D.. USC Laboratory for Environmental Science, USC School ot Medicine. 2025 Zonal Avenue, Los Angeles, CA 90033. DISCUSSION The reduction in flow is small airways is consistent with the observation of distortion of these airways by peribronchial fibrosis in asbestos-exposed individuals observed 50 yr ago4 and recently extended.5 The modest reduction in FEV, ,, reflects the contribution of small airways to the volume expired in the first second. The apparent increase in midflow is consistent with in creased radial traction resulting from fibrosis holding open airways larger than 2 mm in diameter. The rela tive preservation of FEF25.75 in the nonsmoking insula tors and in the smokers as well, seems to confirm the fact that, in general, insulators have stiffer lungs. Thus, in the nonsmoking insulators FEF25_7S was not decreased, in contrast to the overall decrease in flows found in "indus trial bronchitis."6 This was despite a high prevalence of chronic bronchitis (21.6%) in these men. The pattern which emerges for these nonsmoking as bestos-exposed workers is one of decreased airflow in small airways and stiffening of the lung parenchyma (Fig. 1). None of the nonsmokers in this study had severe asbestosis, i.e., a profusion of opacities of 2/2 or greater by ILO criteria. Because of limited data on more ad vanced stages of the disease in nonsmokers, additional subjects with more severe asbestosis will be required to complete this analysis. However, it is predicted that the physiologic course should be that of other interstitial diseases, such as sarcoidosis,7 at least as revealed by spirometry. Other studies of workers have shown that the FVC and FEF2S_7S decrease with increasing exposure measured in particle years and with increasing radiographic change.8'11 These studies included smokers and nonsmokers. Because insulators and shipyard workers included a high proportion of smokers in the REFERENCES 1. ILO International classification of radiographs of pneumoconio ses. 1980, 1981. Occupational Safety and Health Series. Geneva. Switzerland: International Labour Office. 2. ATS Statement. 1979. Snowbird workshop on standardization of spirometry. American Thoracic Society, Medical Section of Amer ican Lung Association. Am Rev Respit Dis 119: 831-38. 3. Miller, A.; Thornton,). C.; W&rshaw. R.; Anderson. H.; Teirstein. A. S.; and Selikoff, I.J. 1985. Mean and instantaneous expiratory flows. FVC and FEV,. Prediction equations for nonsmokers and smokers from a random sample of Michigan, a large industrial state. Sub mitted for publication. 4. Gloyne, S. R. 1933. The morbid anatomy and histology of asbesto sis. Tubercle 14: 550-58. 5. Wright,). L.. and Churg, A. 1984. Morphology of small airway le sions in patient with asbestosis. Human Pathol 15: 68-74. 6. Hankinson,). L.: Reger, R. B.; and Morgan. W. K. 1977. Maximal expiratory flows in coal miners. Am Rev Rcspir Dis 116: 175-80. 7. Miller, A.; Teirstein, A. S.; lackler, I.: Chung. M.: and Silzbach, L. E. 1974. Airways function in chronic pulmonary sarcoidosis with fibro sis. Am Rev Rcspir Dis 109: 179-89. 8. Becklake, M. R.; Fournier-Massey, G.; McDonald. ). C.; Siemiatydki,).; and Rossiter. C. E. 1979. Lung function in relation to chest radiographic changes in Quebec asbestosis workers. I. Methods, re sults and conclusions. Bull Physio-Pathol Resp 6: 637-59. 9. Muldoon, B. C., and Turner-Warwick, M. 1972. Lung function studies in asbestos workers. 8r) Dis Chest 66: 121-32. 10. )odoin, G.; Gibbs, G. W.: Macklem, P. T.; MacDonald. |. C.; and Becklake, M. R. 1971. Early effects of asbestos exposure on lung function. Am Rev Resptr Dis 104: 525-35. 11. Wfeill, H.: Ziskind, M. M.; Waggenspack, C.: and Rossiter, C. E. 1971. Lung function consequences of dust exposure in asbestos cement manufacturing plants. Arch Environ Health 30: 88-97. 12. Rodriquez-Roiin, R.; Merchant, |. E. M.; Cochrane, G. M.; Hickey. B. P. H.; Turner-Warwick, M.; and Clark. T. ). H. 1980. Maximal expiratory flow volume curves in workers exposed to asbestos. Respiration 39: 158-65. 13. Harless. K. W.; Watanabe. S.; and Renzetti |r,, A. D. 1978 The acute effects of chrysotile asbestos exposure on lung function. En viron Res 16: 360-72. November/Oecember 1985 [Viol. 40, (No. 6)1 10003221 295