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Pleural Plaques and Cigarette Smoking in Asbestos Workers William Weiu, M.D.; Richard Levin, M.S.; and Lawrence Goodman, M.D. In a survey of 45 men aged 40 or over who had worked five years or more in an asbestos manufacturing plant the prevalence of pleural plaques was studied with respect to age, duration of asbestos exposure, estimated cumulative asbestos dose, and smoking habit. Plaques were found in 38 to 53% of the men, depending on the interpretation of the chest film reader. Cigarette habit appeared to be the most important factor; the prevalence was lowest in non smokers. intermediate in current smokers, and particularly high in exsmokers. There was some confounding of this relationship by estimated cumulative asbestos dose but such confounding did not seem to be sufficient to explain lully the relationship between the prevalence of plaques and smoking habit. Both factors must be considered in studies of the risk of pleural plaques in asbestos workers. I n a previous report Weiss and Theodos1 described the results of a 1975 chest x-ray survey in two asbestos pro ducts manufacturing plants. Plant A had used only chry solite asbestos throughout its history while Plant B had used both chrysotile and amosite from 1950 to 1964 but only chrysotile before and after this period The preva lences of both pulmonary fibrosis and pleural disease were higher in Plant B. Cigarette smoking was a factor in the prevalence of pulmonary fibrosis and perhaps also of pleural disease at Plant B. Pleural thickening was found in only one of 10 non smokers and in 42% of the 36 current and exsmokers of cigarettes at Plant B. This difference was not quite statisti cally significant (p = 0.074 by Fisher's exact test), but it has stimulated further investigation of the problem by the authors. This paper analyzes the results of the 1977 and 1978 surveys with respect to the relationships between the prevalence of pleural plaques in men aged 40 or over and the factors of age. duration of asbestos exposure, esti mated cumulative dose of asbestos, and cigarette habit. hoffl (he Dtviwon of Oc<upiliOA*l Medicw*. DfpMmtAl of Medic**. MjhrN>mAft Mednil CoM*|f 4ftd Hospitjl 2)0 North Brod Si. PHtUdrlpM. PA 191(12 (IV Wrm snd Mr Itvinl *nd Ihe Department of Dugnotl* Pid*logv (Dr Coodmen) Addrett commonKihont to Dr Went Journal ol Occupational Medicine/Vol. 23, No. 6/June 1981 Method A detailed description of the products and processes in Plant B was provided in the previous report' a summary of which follows. In 1935 this facility was manufacturing asbestos tex tiles, compressed sheet packing, paper, millboard, and molded thermal insulations. Textiles were made of chrysotile asbestos in a dry, dusty process: this operation was discontinued in 1951 Sheet packing was also made only of chrysotile and. because of milling the asbestos, the operation was dustier before the 1950s than it was in later years. Paper and millboard operations were very dusty prior to 1960. but after 1960 process improvcnru-nts led to better conditions Molded insulation was made of chrysotile from 1935 to 1950, thereafter, amosite. which had to be milled dry, was added to the chrysotile until manufacture of these products was discontinued in 1964 In 1948 the plant began to produce corrugated and mono lithic asbestos cement boards made of chrysotile and Portland cement. Asbestos fiber counts were not made until 1972 but have been generally under 2/cm1 in recent years. Because of the lack of counts prior to 1972, the cumulative asbestos exposure (dose) for each employee in this study had to be estimated on a semiquantitative basis A |ob in dex was devised at a meeting of the industrial hygienist (R.L.) with three foremen who had begun work at this plant between 1941 and 1947. Each job was rated as to degree of asbestos exposure on a scale of 1 to 3 (largest exposure). To take into account the change in conditions over time, job ratings were multiplied by three during the period prior to 1951, by two during the period 1951 through 1963. and by one from 1964 on. The employment record of each man was reviewed and an index of cumu lative asbestos exposure was computed by multiplying the job rating, the period rating, and the number of years worked at each job during each period. The maximum in dex recorded in this group of men was 159. Pleural plaques were noted only in men aged 40 or over. There were 69 such employees eligible for examina tion between 1977 and 1978. and 56 (81 %) had 110 kv 3GX 43 cm postero-anterior chest films during one or both of 427 SCF-FA-7550 8004 2037 libit V -- Prevalence ol Pleural Plaques by Ruder. Age. Duration of Aibestos Exposure. Estimated Cumulative Dote ol Asbestos, and Cigarette Habit in Workers Aged 40 or Over. Characteristic Age - years 40-54 55. veers exposed 5 29 30. Cumuieiive dose index 0-19 70-59 60. Cigarette haon ' Nonsmoker Current smoker Exsmoker Total Prevalence et Plaoues Or Ruder w.w LG. * ol % ol Probability % ol Probability NO. Tout NO. Group (Chi Square) No. Group (Chi Squaiol 70 u 9 45 75 56 16 60 70 44 6 30 75 56 18 77 14 31 4 - 79 14 31 9 64 17 36 11 65 1? 77 4 33 19 47 a 4? 14 31 17 86 45 too 74 63 >005 <0 05 >0.05 <0.075 6 40 9 36 5 75 17 40 7 14 1 57 7 41 7 17 6 37 9 64 17 36 >0 05 >0 05 >0 05 <0 05 these annual surveys. Eleven men who had worked for less than live years at this plant were eliminated to allow (or a minimal latent period of five years, leaving 45 in the study The chest films were read by two of the authors (W VV. and l.C) independently without knowledge of the individual's age. work experience, or smoking habit. Pleural plaques were recorded as present when pleural thickening of irregular width was noted along the lateral chest wall, provided it spared the apex and the costophrenic angle, or on the dome of the diaphragm, with or without calcification. A careful smoking history was recorded at each survey. For the purpose of this investigation, each employee was classified according to cigarette habit as a nonsmoker (had never smoked cigarettes), a current smoker, or an ex smoker (had stopped smoking one or more years ago) The statistical significance of differences was deter mined by calculating exact probability by the binomial distribution or by estimating probability by the t test, the chi square test (with Yates' correction when there was only one degree of freedom), one-way analysis of vari ance, or significance limits for the fourfold'table test based on the hypergeometric distribution. Results . There was 31% disagreement between the two chest film readers on the presence of pleural plaques In 11 (24%) of the 45 cases W.W. found plaques when L G. did not and in 3 (7%) L.G. found them when WW. did not This difference was not quite statistically significant at the 0 05 level (p = 0 0574 using the binomial distribution for paired observations). The prevalence of plaques is presented for each reader separately. Table 1 shows that the prevalence of plaques was 53% for W.W. and 38% for L C. Age was not a factor. The data suggest that both duration of asbestos exposure and cumulative dose of asbestos were factors although, be cause of small numbers, three of the four companions did not reach statistical significance at the 005 level However, cigarette habit was found to be an important factor, the prevalence of plaques being particulars high in exsmokers, and the differences were statistically sig nificant for both readers. Only two men had calc plaques (interpreted in both cases by L C) One must consider the possibility that the relationship between pleural plaques and cigarette habit was run founded by the other factors investigated, particularly Tibia 2 - Comparison of Cigarette Habit Groups by Ago, Duration of Asbestos Esposuro, and Estimated Cumulativi Dota of Aibistos In Workers Agsd 40 or Ovar. Charietorlitle Age - years Mean S D. Years ol exposure Mean S D. Cumulative dose index Mean S.D Nonimokors N- 17 Cipiretti Hiblt Current Smokers N It 53 9 6 67 74 SO 17.95 40.90 77.78 53 4 6.16 73 68 14.63 45.37 42.79 Eiimokers N - 14 563 5.17 37 43 907 63 36 28.72 Probability exsmokers vs others. t - 1.41. p > 0 05 exsmokers vs. others t 2 09. P < 0 05 eismokers vs. omers t - 1.76. P > 0 05 AN0VA* lor 3 groups F 1.56. p >0 05 *0ne-wiy analysis ol veriince 426 Pleural Plaques and Cigarette Smoking/Weiss, Levin, and Coodman 8004 2038 t I (, V- dvgree and duration of asbestos exposure. Table 2 shows tK.it the smoking groups were similar in age. With respect to duration of asbestos exposure, nonsmokers and current smokers were similar but exsmokers averaged eight years more of work at the plant this difference being statisti cally significant. With respect to cumulative asbestos dose, the same pattern appeared: current smokers were similar to nonsmokers, but exsmokers had an average indpx which was 40 to 55% higher than the average index for the other two groups Although these differences may be ini|K>rtant, they are not statistically significant by two different methods of analysis. When the men were distributed according to both cumulative dose of asbestos and cigarette habit the prev alence of plaques read by W.W. varied with respect to both factors (Table 3). The data suggest that the preva lence of plaques is high in exsmokers at any asbestos dosage but that in nonsmokers and current smokers the prevalence increases with increasing asbestos dose. Un fortunately. cross-classification by the two factors results in cells with very small numbers. However, if the data in the two lower asbestos dose categories are combined, then plaques were found in 6 of 21 nonsmokers and cur rent smokers compared with 6 of 7 exsmokers. This differ ence is statistically significant at the 0.05 level using sig nificance limits for the fourfold table test based on the hypergeometrical distribution.* The findings were similar for plaques read by L.C. but the differences were not as clear-cut and were not statistically significant at the 005 level Discussion Several investigators have noted an association be tween pleural thickening and smoking in workers exposed to asbestos In a large survey of English naval dockyard workers exposed to chrysotile, amosite, and crocidolite, P C Harries et al! found pleural thickening in 2.7% of 5.552 nonsmokers. 4 9% of 12.798 smokers, and 6.4% of 4.990 exsmokers The prevalence of pleural thickening tended to fall slightly with increasing cigarette dosage In recent published reports of the studies of these dotkyard workers. Rossiter et al'* have provided more details for segments of this population In a sample of 1.2IX) men who were aged 50 to 59, pleural thickening was separated into diffuse disease and. plaques.1 Only the presence of plaques was related to the duration of expo sure to asbestos and there was an excess of plaques in ex smokers (29 5%) compared with the prevalence in smokers (23 9%) and in nonsmokers (231%) The preva lence of pleural calcification was different 8 8% among nonsmokers. 3 5% among smokers, and 61 % among ex smokers A nine-year (1966-1975) follow-up study of 253 dockyard workers* found increases in the prevalence of diftuM- pleural thickening, almost entirely limited to those men who had stopped smoking after 1966, and of pleural plaques, with the greatest increase (from 10% to 23%) in smokers, but little change in the prevalence of calcified plaques HillerdaP reported a study of pleural plaques in chest s-r.i\ surveys of the general population in the Swedish *| li .imeiil.i I nmi'iIii Mil I il |H I**' 1*1 journal ol Occupational Medictne/Vol. 23. No. 6/June 1981 Table 3. -- Prevalence ol Pltunl Plaquis (Read by W.W.) by Estimated Cumulative Dose ol Asbestos and Cigarette Habit in Men Aged 40 or Over. Asbestos Dose and Cigarette Habit Asbestos inoex under 20 Nonsmoker Current smoker Exsmoker Asbestos index 20-59 Nonsmoker Current smoker Exsmoker Asbestos index 604 Nonsmoker Current smoker Exsmoker Total No. ot Man In Croup 5 6 1 3 5 6 4 6 7 45 No. ot Mm with Plaques 1 2 1 2 5 2 5 5 24 county of Uppsala. Of 492 men with plaques, 354 were in terviewed and it was found that 79% were or had been smokers. The expected frequency in men of the same age and occupation is 55%. In a survey of 197 Swedish asbes tos workers. Hedenberg et al* found pleural plaques in 30% of 103 smokers and 19% of 94 nonsmokers Thus, there is general consistency between the reports from England and Sweden and the data reported m the present study, especially with respect to exsmokers in those studies in which these have been separated from current smokers Unfortunately the studies cited from the literature have no information on the possible confound ing of this relationship by degree of asbestos exposure The data in this study suggest that there may be some confounding While the association between the preva lence of plaques and smoking was somewhat stronger than that between plaques and cumulative asbestos dosage, it must be remembered that the estimates oi dosage were crude. It is uncertain whether the finding of 40 to 55% greater asbestos exposure in exsmokers could account fora prevalence of plaques which was more than double that in the other groups Conclusions an- nStrained by the small number of workers in this mvestig.i tion. A clear-cut answer to the question as to whether tinassociation between plaques and smoking is spurious will require a much larger research effort, preferably in a cohort study. The hypothesis that smoking is a factor m the patho genesis of asbestos-related pleural plaques is a plausible one despite the fact that the mechanism by which inhaled asbestos fibers produces fibrous plaques in the parietal pleura is unknown Smoking is detrimental to carious aspects of pulmonary function although the effect on the clearance of particulate matter is not clear7 A recent study by Cohen et al* shows, by the use of inhaled mag netic dust (magnetite), that long-term dust clearance is impaired in smokers: 50% retention compared to 10% in nonsmokers It might well be that once smoking has damaged the clearance mechanisms, cessation of smok ing could be more harmful in this type of defense than continued smoking because the short-term eftec t of < iga rette smoking is to enhance deep bronchial clearance transiently in some people* and smokers mav become dependent on this effect to maintain clearance I his 429 8004 2039 could explain an increaxd frequency of pleural plaques in exsmokers because damaged clearance mechanisms unaided bv continued smoking may lead to higher "effec tive ' doses of asbestos in the tissues. The clinical significance of a relationship between the prevalence of pleural plaques and smoking depends on the clinical significance of plaques. The immediate impor tance of these lesions is negligible but there is some sus picion that plaques may be indicators of an enhanced risk of lung cancer'" " and mesothelioma " With respect to lung cancer risk the evidence is equivo cal Kiviluoto et al' found 700 cases of calcified plaque in 6.000 adults during a mass chest x-ray survey in Tuusniemi commune, Finland, in 1962. The lung cancer incidence between 1962 and 1977 was almost identical to the incidence in controls without plaques in Maaninka commune. 13 and 14. respectively. It may be important to note that this study was limited to calcified plaques. In a case-control study of 69 lung cancer cases there was an elevated risk of lung cancer of 2.8 only when there was pulmonary fibrosis in addition to calcified plaques. Infor mation on smoking habits was not provided. Edge" has reported an increased incidence of lung cancer in 429 older British shipyard workers with pleural plaques unassociated with pulmonary fibrosis found be tween 1964 and 1971 who were compared with a matched control group of 429 men in another city where there was neither known asbestos exposure nor plaques. After excluding six men with lung cancer who had clinical evidence of tumor at the time observation was begun in the men with plaques, the relative risk was 3.25 (13 cases in the men with plaques compared to 4 in the controls, chi square with Yates' correction = 3.84, p = 005). How ever. this comparison is probably invalid because only 231 of the 429 men with plaques were discovered by routine chest films and the remaining 198 were found by clinic or hospital films whereas all 429 controls had routine films. Thus, there was undoubtedly some selec tion bias operating to increase the incidence of lung can cer in the men with plaques. Comparing only the groups that had routine films, six (2.6%) of 231 men with plaques and four (09%) of 429 controls developed lung cancer, a difference which is not statistically significant at the 0.05 level Furthermore, half the lung cancer cases in the men with plaques were diagnosed in the first two years of follow-up and therefore these individuals presumably had their tumors at the time observation began. After ex clusion of the early cases, the relative risk, as compared to the incidence of lung cancer in the general population. remained at 1.0 until after six years of follow-up it rose to 2.1 (6 cases compared to 2.6 expected), which also u not statistically significant at the 0.05 level Most importantly, no smoking habit information was available for adjust ment of the relative risk. A similar problem indicating selection bias in the men with plaques operated with respect to the incidence of mesothelioma: most of the cases occurred early in the follow-up period and only two developed alter six yr.ir-, of follow-up. However, mesothelioma is so rare m tlv general population that even two cases in the mm wnii plaques is suspicious, especially since mi-soihrlKiiii.i is not related to smoking. Thus, at present the prognostic significance of pleural plaques with regard to the risk of lung cancer is doubtiol In the absence of smoking-habit data, no conclusions are warranted. If plaques are related to smoking as well as to asbestos exposure and if lung cancer is similarly related, then any association between plaques and lung cancer is likely to be spurious. References 1 Weisi W and Theodos PA Pleuropulmonary disease among asbeitos workers in relation to smoking and type of exposure / Occvp Med 20 341-34$, 1976 2 Harries PC. Rossiter CE. and Coles RM: Royal Naval Dockyards Asbestosis Research Project. Report No 1. December 1975 3. Rossiter CE and Harries PC: U K Naval Dockyards Asbestosis Study. Survey of the sample population aged S0-S9 years Sr I ind Med 36 281-291.1979. 4 Rossiter CE. Heath IR. and Harriet PC Royal Naval Dockyards Asbestosis Research Protect Nine-year <ollow-up study of men e>posed to asbestos in Devonport Dockyard / Roy Soc Med7} 3)7144 1980 $ Hillerdal C Pleural plaques in a health survey material Scant/ / Resprr Du S9 257-26). 1978 6 Hedenberg l, Hermansson l, Liden MA. and Thunnger C Directed health survey of workers exposed to asbestos Ltk.irudmr.gen 78 4151-4152, 1976 (Abstract in International Cancer Research Data Bank Cancergram on Environmental and Occupational Carcmo genesis. Series CK02, No 4, April 1979. p 6. National Cancer Institute! 7 Smoking and Health. A Report of the Surgeon General U 5 Department of Health. Education, and Welfare. DHfM Puhluatinn No (PHSl 79-50066.1979. Section 6. pp 6-32 and 6-33 6 Cohen D. Arai SF. and Brain ID. Smoking impairs long-term ilust clearance from the lung Science 204 514-517. 1979 9 Albert RE. Peterson HT. Bohning DE. and lippmann M Slwi term effects of cigarette smoking on bronchial clearance in humanArch Environ Health 31 361-3b7.1975 10 Kiviluoto R. Meurmin LO. and Hakama M Pleural plaaurs and neoplasia in Finland Ann NY Acad id 330 31-3). 1979 11 Edge IR Incidence of bronchial carcinoma in shipyard workers with pleural plaques Ann NY Acad Sci 330 289 294. 1979 430 Pleural Plaques and Cigarette Smoking/Weiss, Levin, and Goodman