JONES. J.S.P., SMITH, P.G., POOLEY, F.D., BERRY, G., SAWLE, G.W., MADELEY, R.J., WIGNALL, B.K. The consequences of exposure to asbestos dust in a wartime gas-mask factory. In: Wagner, J.C. (ed.1. Biological Effects of Mineral Fibres. Vol. 2. IARC Scientific Pub. No. 30. Lyon, International Agency for Research on Cancer, 1980, pp. 637653. KAGAN, E., SOLOMON, A., COCHRANE, J.C., KUBA, P., ROCKS, P.H., WEBSTER, I. Immunological studies of patients with asbestosis: II. Studies of circulating lymphoid cell numbers and humoral immunity. Clinical and Experimental Immunology 28(2):268-275, May 1977. KAHN, H.A. The Dorn study of smoking and mortality among U.S. veterans: Report on eight and one-half years of observation. In: Haenszel, W. (ed.). Epidemiological Approaches fo the Study of Cancer and Other Chronic Diseases. National Cancer Institute Monograph No. 19. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, National Cancer Institute, January 1966, pp. l-125. KANDASWAMI, C., O'BRIEN, P.J. Pulmonary metabolism of benzo [alpyrene: Effect of asbestos. Biochemical Pharmacology 30(7):811-814, April 1,1981. KANG, K.-Y., SERA, Y., OKOCHI, T., YAMAMURA, Y. T lymphocytes in asbestosis. New England Journal of Medicine 291(14):735-736, October 3, 1974. KAPLAN, H., RENIER, A., JALJRAND, M.C., BIGNON, J. Sister chromatid ex- changes in mesothelial cells cultured with chrysotile flbres. In: Brown, R.C., Gormley, I.P., Chamberlain, M., Davies, R. (eds.). The In Vitro Effects of Mineral Dusts. London, Academic Press, 1980, pp. 251-253. KILBURN, K.H. Cigarette smoking does not produce or enhance the radiologic appearance of pulmonary fibrosis. American Journal of Industrial Medicine 2(31:305308, 1981. KOLONEL, L.N., HIROHATA, T., CHAPPELL, B.V., VIOLA, F.V., HARRIS, D.E. Cancer mortality in a cohort of naval shipyard workers in Hawaii: Early findings. Journal of the National Cancer Institute 64(4):739-743, April 1980. LAKOWICZ, J.R.. BEVAN, D.R. Effects of asbestos, iron oxide, silica, and carbon black on the microsomal availability of benzo[a]pyrene. Biochemistry 18(23):517& 5176, November 13,1979. LAKOWICZ, J.R., McNAMARA, M., STEENSON, L. Particle-mediated membrane uptake of chemical carcinogens studied by fluorescence spectroscopy. Science 199(4324):305-307, January 20,197s. LANDESMAN, J.M., MOSSMAN, B.T. Induction of ornithine decarboxylase in hamster tracheal epithelial cells exposed to asbestos and 1%O-tetradecanoylphor- bol-13-acetate. Cancer Research 42(9):3669-3675, September 1982. LANGE, A. An epidemiological survey of immunological abnormalities in asbestos workers: II. Serum immunoglobulin levels, Environmental Research 22(1):176183, June 1980. LANGLANDS, J.H.M., WALLACE, W.F.M., SIMPSON, M.J.C. Insulation workers in Belfast: 2. Morbidity in men still at work. British Journal of Industrial Medicine 28(3~:217-225. July 1971. LI, V.C., KIM, Y.J., TERRY, P.B., CUTHIE, J.C., ROTER, D., EMMETT, E.A., HARVEY, A., PERMUTT, S. Behavioral, attitudinal, and physiologic characteris- tics of smoking and nonsmoking asbestos-exposed shipyard workers. Journal of Occupational Medicine 25(123:864870, December 1983. LIDDELL, F.D.K., GIBBS, G.W.. MCDONALD, J.C. Radiological changes and fibre exposure in chrysotile workers aged 66-69 years at Thetford Mines. Annals of Occupational Hygiene 26(1/4):88%898,1982. LIDDELL, F.D.K., THOMAS, DC., GIBBS, G.W., MCDONALD, J.C. Fibre exposure and mortality from pneumoconiosis, respiratory and abdominal malignancies in chrysotile production in Quebec 192&75. Annals of the Academy of Medicine, Singapore 13(2, Supp.):340-344, April 1984. 276 MARSH, J.P., MOSSMAN, B.T. Ornithine decarboxylase (ODC) activity and mitogen- ic response in tracheal epithelial cells exposed to fibrous and nonfibrous analogs of asbestos and glass: Importance of serum and epidermal growth factor (EGFI. (abstract). Proceedings of the 75th annual meeting of the American Assoctatton for Cancer Research 25143, March 1984. MARX, J.L. Tumor promoters: Carcinogenesis gets more complicated. Science 201(43541:515-518, August 11, 1978. McCORD, J.M., WONG, K. Phagocyte-produced free radicals: Roles in cytotoxicity and inflammation. In: Fridovich, I. ced.1. Oqgen Free Radicals and Tissue Damage. Ciba Foundation Symposium 65. Amsterdam, Excerpta Medica, 1979. pp. 343-367. McDERMO'IT, M., BEVAN, M.M., ELMES. P.C.. ALLARDICE, J.T., BRADLEY, A.C. Lung function and radiographic change in chrysotile workers in Swaziland. British Journal oflndustrial Medicine 39(4):338-343. November 1982. MCDONALD, A.D., FRY, J.S., WOOLLEY, A.J., MCDONALD. J.C. Dust exposure and mortality in an American chrysotile textile plant. British Journal of Industrial Medicine 40(4):361-367, November 1983a. MCDONALD, A.D., FRY, J.S., WOOLLEY. A.J., MCDONALD, J.C. Dust exposure and mortality in an American factory using chrysotile, amosite, and crocidolite in mainly textile manufacture. British Journal of Industrial Medicine 40t4):368-374, November 1983b. MCDONALD, A.D., FRY, J.S., WOOLLEY, A.J., MCDONALD, J.C. Dust exposure and mortality in an American chrysotile asbestos friction products plant. British Journal of Industrial Medicine 41(2):151-157, May 1984. MCDONALD, J.C., LIDDELL, F.D.K., GIBBS, G.W.. EYSSEN, G.E., MCDONALD, A.D. Dust exposure and mortality in chrysotile mining, 191c75. British Journal of Industrial Medicine 37(11:11-24, February 1980. MCKAY, F.W., HANSON, M.R., MILLER, R.W. (eds.1. Cancer Mortality in the United States: 1950-1977. National Cancer Institute Monograph No. 59. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, NIH Pub. No. 82-2435, April 1982. McLEMORE, T.L., JENKINS, W.T., ARNOTT, MS., WRAY, N.P. Aryl hydrocarbon hydroxylase induction in mitogen-stimulated lymphocytes by benzanthracene or cigarette tars adsorbed to asbestos fibers. Cancer Letters 7(2/3):171-177, July 1979. McMILLAN, G.H.G., PETHYBRIDGE, R.J., SHEERS, G. Effect of smoking on attack rates of pulmonary and pleural lesions related to exposure to asbestos dust. British Journal of Industrial Medicine 37(3):26%272, August 1980. McMILLAN, G.H.G., SHEERS, G., PETHYBRIDGE, R.J. A radiological follow-up study of the effect of asbestos in dockyard workers in Portsmouth. Journal of the Rowval Naval Medical Service 6x21: 63-74, Summer 1979. MEDICI, T.C., BUERGI, H. The role of immunoglobulin A in endogenous bronchial defense mechanisms in chronic bronchitis. American Review of Respiratory Disease 103(6):784-791, June 1971. MEURMAN, L.O., KIVILUOTO, R., HAKAMA, M. Mortality and morbidity of employees of anthophyllite asbestos mines in Finland. In: Bogovski, P., Gilson, J. C., Timbrell, V., Wagner, J. C., Davis, W. (eds.). Biological Effects ofAsbestos. IARC Scientific Pub. No. 8. Lyon, International Agency for Research on Cancer, 1973, pp. 199-202. MEURMAN, L.O., KIVILUOTO, R., HAKAMA, M. Mortality and morbidity among the working population of anthophyllite asbestos miners in Finland. British *Journal of Industrial Medicine 31(2):105112, April 1974. MEURMAN, L.O., KIVILUOTO, R., HAKAMA, M. Combined effect of asbestos exposure and tobacco smoking on Finnish anthophyllite miners and millers. Annals of the Neu, York Academ.v of Sciences 330:491-495, December 14. 1979. 277 MITRLJKA, B.M., RAWNSLEY, H.M., VADEHRA, D.V. Animals for Medical Research: Models for the Stud:4 of Human Disease. New York, John Wiley and Sons, 1976,591 pp. MILLER, L., SMITH, W.E., BERLINER, S.W. Tests for effect of asbestos on benzo[a]pyrene carcinogenesis in the respiratory tract. Annals of the New York Academy of Sciences 132:489-500,1965. MILLER, L.G., GOLDSTEIN, G., MURPHY, M., GINNS, L.C. Reversible alterations in immunoregu!atory T cells in smoking: Analysis by monoclonal antibodies and flow cytometry. Chest 82(51:526-529, November 1982. MILLER, L.C., SPARROW, D., GINNS, L.C. Asbestos exposure correlates with alterations in circulating T cell subsets. Clinical and Experimental Immunology 51(1):11Ck116, January 1983. MOSSMAN, B.T., CRAIGHEAD, J.E. Use of hamster tracheal organ cultures for assessing the cocarcinogenic effects of inorganic particulates on the respiratory epithelium. Progress in Experimental Tumor Research 24~37-47, 1979. MOSSMAN, B.T., CRAIGHEAD, J.E. Mechanisms of asbestos carcinogenesis. Enui- ronmental Research 25:269-280,1981. MOSSMAN, B.T., CRAIGHEAD, J.E. Comparative cocarcinogenic effects of kaolin, hematite, carbon and crocidolite asbestos in implanted tracheal organ cultures. In: Znhaled Particles, Vol. 5. London, Pergamon Press, 1982, pp. 553-568. MOSSMAN, B.T., CRAIGHEAD, J.E., MacPHERSON, B.V. Asbestos-induced epitheli- al changes in organ cultures of hamster trachea: Inhibition by retinyl methyl ether. Science 207(4427):311-313, January 18, 1980. MOSSMAN, B.T., EASTMAN, A., BRESNICK, E. Asbestos and benzo[a]pyrene act synergistically to induce squamous metaplasia and incorporation of [3H]thymidine in hamster tracheal epithelium. Carcinogenesis 5(11):1401-1404, November 1984. MOSSMAN, B.T.. EASTMAN, A., LANDESMAN, J.M., BRESNICK, E. Effects of crocidolite and chrysotile asbestos on cellular uptake and metabolism of ben- zo[a]pyrene in hamster tracheal epithelial cells. Environmental Health Perspec- tives 51:331-335, September 1983. MOSSMAN. B.T., HALLERON, P.A., CRAIGHEAD, J.E. Stimulation of Na+-K- ATPase activity in tracheal epithelial cells after exposure to crocidolite asbestos. (abstract). Journal of Cell Biology 83(3):288a, December 1979. MOSSMAN, B.T., LANDESMAN, J.M. Importance of oxygen free radicals in asbestos- induced injury to airway epithelial cells. Chest 83(5):5OS-515, May 1983. MOSSMAN, B., LIGHT, W.. WEI, E. Asbestos: Mechanisms of toxicity and carcinoge- nicity in the respiratory tract. Annual Retlieu of Pharmacology and Toxicology 23:595-615, 1983. MULDOON. B.C.. TURNER-WARWICK, M. Lung function studies in asbestos workers, Brrtlsh Journal of Diseases of the Chest 66:121-132, April 1972. MURPHY, R.L.H., Jr., FERRIS, B.G., Jr.. BURGESS, W.A., WORCESTER, J., GAENSLER, E.A. Effects of low concentrations of asbestos: Clinical, environmen- tal, radiologic and epidemiologic observations in shipyard pipe coverers and controls. LVeu EngIand Journal of Medicine 285(231:1271-1278, December 2, 1971. MURPHY, R.L.H.. Jr., GAENSLER. E.A., FERRIS, B.G., FITZGERALD, M., SOLLI- DAY. N., MORRISEY, W. Diagnosis of "asbestosis": Observations from a longitudi- nal survey of shipyard pipe coverers. American Journal of Medicine 65(3X488-498, September 1978. MURPHY, R.L.H.. Jr., GAENSLER. E.A., REDDING, R.A.. BELLEAU, R., KEELAN, P.J.. SMITH, A.A., GOFF, A.M., FERRIS, B.G., Jr. Low exposure to asbestos: Gas exchange in ship pipe coverers and controls. Archives of Environmental Health 2514):253-264, October 1972. NATIONAL RESEARCH COUNCIL. Asbestiform Fibers: Nonoccupational Health Risks. National Research Council, Committee on Nonoccupational Health Risks of Asbestiform Fibers. Washington, D.C., National Academy Press, 1984,334 pp. 278 NATUSCH, D.F.S., WALLACE, J.R., EVANS, CA., Jr. Toxic trace elements: Preferential concentration in respirable particles. Science 183(4121):202-204, January 18,1974. NEWHOUSE, M.L., BERRY, G. Patterns of mortality in asbestos factory workers in London. Annals of the Xew York Academy of Sciences 33053-60, December 14, 1979. NICHOLSON, W.J., PERKEL, G., SELIKOFF, I.J. Occupational exposure to asbestos: Population at risk and projected mortality-198G2030. American Journal of Industrial Medicine 3(4):259-311, 1982. NICHOLSON, W.J., SELIKOFF, I.J., SEIDMAN, H., LILIS. R., FORMBY, P. Long- term mortality experience of chrysotile miners and millers in Thetford Mines, Quebec. Annals of the New York Academ.v of Sciences 330:11-21, December 14, 1979. ONTARIO, ROYAL COMMISSION. Report of the Ro.val Commission on Matters of Health and Safety Arising From the Use of Asbestos In Ontario. Vol. 1. Toronto, Ontario Ministry of the Attorney General, 1984,313 pp. OSHIMURA, M., HESTERBERG, T.W., TSLJTSUI, T., BARRE'IT, J.C. Correlation of asbestos-induced cytogenetic effects with cell transformation of Syrian hamster embryo cells in culture. Cancer Research 44(111:5017-5022, November 1984. PEARLE, J.L. Smoking and duration of asbestos exposure in the production of functional and roentgenographic abnormalities in shipyard workers. Journal of Occupational Medicine 24(11:37-%0, January 1982. PETO, J. Dose-response relationships for asbestos-related disease: Implications for hygiene standards: Part 2. Mortality. Annals of the Neu York Academy of Sciences 330:195-203, December 14,1979. PETO, J. Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. In: Wagner, J.C. ted.). Biological Effects of Mineral Fibres. Vol. 2. IARC Scientific Pub. No. 30. Lyon, International Agency for Research on Cancer, 1980, pp. 829836. PETO, J., DOLL, R., HOWARD, S.V., KINLEN, L.J., LEWINSOHN, H.C. A mortality study among workers in an English asbestos factory. British Journal of Industrial Medicine 34(3):169-173, August 1977. PYLEV, L.N., SHABAD, L.M. Some results of experimental studies in asbestos carcinogenesis. In: Bogovski, P., Gilson, J.C., Timbrell, V., Wagner, J.C. (eds.1. Biological Effects of Asbestos. IARC Scientific Pub. No. 8. Lyon, International Agency for Research on Cancer, 1973, pp. 99-105. REEVES, A.L. The carcinogenic effect of inhaled asbestos fibers. Annals of Clinical and Laboratory Science 6(5):459-466, September-October 1976. REEVES, A.L., PURO, H.E., SMITH, R.G. Inhalation carcinogenesis from various forms of asbestos. Environmental Research 8(21:178202, October 1974. REGAN, G.M., TAGG, B., WALFORD, J., THOMSON, M.L. The relative importance of clinical, radiological and pulmonary function variables in evaluating asbestosis and chronic obstructive airway disease in asbestos workers. Clinical Science 41(6):569-582, December 1971. REISS, B., SOLOMON, S., TONG, C., LEVENSTEIN. M., ROSENBERG, S.H., WILLIAMS, G.M. Absence of mutagenic activity of three forms of asbestos in liver epithelial cells. Environmental Research 27:389-397, April 1982. ROBINSON, C., LEMEN, R., WAGONER, J.K. Mortality patterns, 194(X1975, among workers employed in an asbestos textile friction and packing products manufactur- ing facility. In: Lemen, R., Dement, J.M. (eds.). Dusts and Diseases. Park Forest South, Illinois, Pathatox Publishers, Inc., 1979, pp. 131-143. RODRIGUEZ-ROISIN, R., MERCHANT, J.E.M., COCHRANE, G.M., HICKEY, B.P.H., TURNER-WARWICK, M., CLARK, T.J.H. Maximal expiratory flow volume curves in workers exposed to asbestos. Respiration 39(3):158-165. 1980. 279 ROM, W.N. LIVINGSTON, G.K., CASEY, K.R., WOOD, S.D., EGGER, M.J, CHIU, G.L., JEROMINSKI, L. Sister chromatid exchange frequency in asbestos workers. Journal of the National Cancer Institute 70(1):45-48, January 1983. ROSSITER, C.E., BERRY, G. The interaction of asbestos exposure and smoking on respiratory health. Bulletin Europeen de Physiopathologie Respiratoire 14(21:197- 204,1978. ROSSITER, C.E., COLES, R.M. HM Dockyard, Devonport: 1947 mortality study. In: Wagner, J.C. (ed.). Biological Effects of Mineral Fibres. Vol. 2. IARC Scientific Pub. No. 30. Lyon, International Agency for Research on Cancer, 1980, pp. 713-721. ROSSITER, C.E., HARRIES, P.G. UK naval dockyards asbestosis study: Survey of the sample population aged 50-59 years. British Journal of hdustrial Medicine 36(41:281-291, November 1979. ROSSITER, C.E., WEILL, H. Synergism between dust exposure and smoking: An artifact in the statistical analysis of lung function? Bulletin de Physio-Pathologic Respiratorre 10(5):717-725, September-October, 1974. RUBINO, G.F., PIOLA'ITO, G., NEWHOUSE, M.L., SCANSE'ITI, G., ARESINI, G.A., MURRAY, R. Mortality of chrysotile asbestos workers at the Balangero mine, northern Italy. British Journal of Industrial Medicine 36(3):187-194, August 1979. SAMET, J.M., EPLER, G.R., GAENSLER, E.A., ROSNER, B. Absence of synergism between exposure to asbestos and cigarette smoking in asbestosis. American Review of Respiratory Disease 120(1):75-82, July 1979. SEIDMAN, H., SELIKOFF, I.J., HAMMOND, E.C. Short-term asbestos work exposure and long-term observation. Annals of the New York Academy of Sciences 330:61-89, December 14,1979. SELIKOFF, I.J., HAMMOND, E.C., CHURG, J. Asbestos exposure, smoking, and neoplasia. Journal of the American Medical Association 204(21:104-112, April 8, 1968. SELIKOFF, I.J., HAMMOND, E.C., SEIDMAN, H. Mortality experience of insulation workers in the United States and Canada, 1943-1976. Annals of the New York Academy of Sciences 330:91-116, December 14,1979. SELIKOFF, I.J., HAMMOND, E.C., SEIDMAN, H. Latency of asbestos disease among insulation workers in the United States and Canada. Cancer 46(12):27362740, December 15,198O. SELIKOFF, I.J., LEE, D.H.K. Asbestos and Disease. New York, Academic Press, 1978, 549 pp. SELIKOFF, I.J., NICHOLSON, W.J., LILIS, R. Radiologicai evidence of asbestos disease among ship repair workers. American Journal of Industrial Medicine 1(11:9-22, 1980. SELIKOFF, I.J., SEIDMAN. H., HAMMOND, E.C. Mortality effects of cigarette smoking among amosite asbestos factory workers. Journal of the National Cancer Institute 65(31:507-513, September 1980. SHABAD, L.M., PYLEV, L.N., KRISVOSHEEVA, L.V., KULAGINA, T.F., NEMEN- KO. B.A. Experimental studies on asbestos carcinogenicity. Journal of the .VafionaZ Cancer Znsfitute 52~41:11751187. April 1974. SHATOS, M.. MOSSMAN, B.T. Macrophage-mediated transfer of asbestos to tracheal epithelium in vitro. American Retlieu! of Respiratory Disease 127:168,1983. SILVERMAN, N.A., POTVIN. C., ALEXANDER, J.C., Jr., CHRETIEN, P.B. In vitro lymphocyte reactivity and T-cell levels in chronic cigarette smokers. Clinical and Experimental Immunology 22(2):285-292, November 1975. SIRACLJSA, A., FIORE, M., SCIELZO, R., CANALICCHI, P., ROSSI, L., FRENQUEL- LUCCI, A.. CALCAGNI, A.M., CICIONI, C. Small airways disease after short term occupational asbestos exposure. La Medicina del Lavoro 74(1):13-22, January- February 1983. SKERFVING, S., KORSGAARD, R., STIKSA, G., SIMONSSON, B.G. AHH inducibili- ty in Swedish workers exposed to asbestos. IRCS Medical Science: Social and Occupational Medicine 8(7/91:532-533, July-September 1980. SLAGA, T.J., FISCHER, SM., WEEKS, C.E., KLEIN-SZANTO, A.J.P., REINERS, J. Studies on the mechanisms involved in multistage carcinogenesis in mouse skin. Journal of Cellular Biochemistry 18(1):99-119,1982. SMITH, M.A., EVANS, J., STEEL, CM. Age-related variation in proportion of circulating T cells. Lancet 2(7886):922-924, October 19. 1974. SMITH, W.E., MILLER, L., CHURG, J. Respiratory tract tumors in hamsters after intratracheal benzo[a]pyrene with and without asbestos. (abstractt. Proceedings of the American Association for Cancer Research 9:65, March 1968. TEASDALE, C., THATCHER, J., WHITEHEAD, R.H., HUGHES, L.E. Age depen- dence ?f T lymphocytes. Lancet 1(79741:141C-1411, June 26,1976. THOMAS, H.F., BENJAMIN, I.T.. ELWOOD, P.C.. SWEETNAM, P.M. Further follow-up study of workers from an asbestos cement factory. British Journal of Industrial Medicine 39(3):273-276, August 1982. TOPPING, D.C., NETTESHEIM. P. Two-stage carcinogenesis studies with asbestos in Fischer 344 rats. Journal of the National Cancer Institute 65(3):627-630, Septem- ber 1980. TOPPING, D.C., NETTESHEIM, P., MARTIN, D.H. Toxic and tumorigenic effects of asbestos on tracheal mucosa. Journal OfEnvironmental Patholoa, and Toxicology 3(5/6):261-275, June-July 1980. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE. Smoking and Health; A Report of the Surgeon General. U.S. Department of Health, Education, and Welfare, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health, DHEW Pub. No. (PHS17950066, 1979, 1136 pp. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. The Health Conse- quences of Smoking for Women: A Report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health, 1980,359 pp. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. The Health Conse- quences of Smoking: The Changing Cigarette. A Report of the Surgeon GeneMl. U.S. Department of Health and Human Services, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health, DHEW Pub. No. (PHS)81-50156,1981,252 pp. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. The Health Conse- quences of Smoking: Cancer. A Report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health, DHEW Pub. No. (PHS)82- 50179,1982,322 pp. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. The Health Conse- quences of Smoking: Cardiovascular Disease. A Report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health, DHEW Pub. No. (PHS)8&50204,1983,388 pp. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. The Health Conse- quences of Smoking: Chronic Obstructive Lung Disease. A Report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service, Office of the Assistant Secretary for Health, Office on Smoking and Health, DHEW Pub. No. (PHS)84-50205,1984,568 pp. U.S. PUBLIC HEALTH SERVICE. Smoking and Health. Report of the AdLlison Committee to the Surgeon General of the Public Health Sewice. U.S. Department of Health, Education, and Welfare, Public Health Service, Centers for Disease Control, PHS Pub. No. 1103,1964,387 pp. 281 VARPELA, E., SAVILAHTI. E., LOKKI, 0. Serum immunoglobulin A in chronic bronchial inflammation. Scandinavian Journal of Respiratoq Diseases 58(1):33- 40, 1977. VORWALD, A.J., DURKAN, T.M.. PRATT, P.C. Experimental studies of asbestosis. Archives of Industrial Hygiene and Occupational Medicine 3(1):1-13, January 1951. WAGNER, J.C. Asbestosis in experimental animals. British Journal of Industrial Medicine 20:1-12, 1963. WAGNER, J.C., BERRY, G., SKIDMORE, J.W., TIMBRELL, V. The effects of the inhalation of asbestos in rats. British Journal ofcancer 29(3):252-269, March 1974. WAGNER, M.M.F., CAMPBELL, M.J., EDWARDS, R.E. Sequential immunological studies on an asbestos-exposed population: I. Factors affecting peripheral blood leukocytes and T lymphocytes. Clinical and Experimental Immunology 38(2):323- 331, November 1979. WALKER, A.M. Declining relative risks for lung cancer after cessation of asbestos exposure. Journal of Occupational Medicine 26(6):422-426, June 1984. WARR, G.A., MARTIN, R.R. Histochemical staining and in vitro spreading of human pulmonary alveolar macrophages: Variability with cigarette smoking status. Journal of the Reticuloendothelial Society 23clk53-62, January 1978. WEBSTER, I. The pathogenesis of asbestosis. In: Shapiro, H.A. (ed.1. Pneumonoco- niosis: Proceedings of the ZnternationaL Conference, Johannesburg, 1969. London, Oxford University Press, 1970, pp. 117-119. WEHNER, A.P., BUSCH, R.H., OLSON, R.J., CRAIG, D.K. Chronic inhalation of asbestos and cigarette smoke by hamsters. Environmental Research 10(3):368-383, December 1975. WEILL, H., HUGHES, J., WAGGENSPACK. C. Influence of dose and fiber type on respiratory malignancy risk in asbestos cement manufacturing. American Review ofRespiratory Disease 120(2):345-354, August 1979. WEILL, H.. ZISKIND, M.M., WAGGENSPACK, C., ROSSITER, C.E. Lung function consequences of dust exposure in asbestos cement manufacturing plants. Archioes of Environmental Health 3@2):88-97, February 1975. WEISS, W. Cigarette smoking and diffuse pulmonary fibrosis: A preliminary report. Archioes of Environmental Health 14(43:564-568, April 1967. WEISS, W. Cigarette smoking and diffuse pulmonary fibrosis. American Review of Respiratory Disease 9%1):67-72, January 1969. WEISS, W. Cigarette smoking, asbestos, and pulmonary fibrosis. American Review of Respiratory Disease 104(21:223-227. August 1971. WEISS, W. Cigarette smoke, asbestos, and small irregular opacities. American Review of Respiratory Disease 130(2):293-301, August 1984. WEISS, W.. LEVIN, E., GOODMAN, L. Pleural plaques and cigarette smoking in asbestos workers. Journal of Occupational Medicine 23t6k427-430, June 1981. WEISS, W., THEODOS, P.A. Pleuropulmonary disease among asbestos workers in relation to smoking and type of exposure. Journal of Occupational Medicine 20(51:341-345, May 1978. WERNER, J.B. Problems with the measurement of radiological change. In: Wagner, J.C. red.). Biological Effects of Mineral Fibres. Vol. 2. IARC Scientific Pub. No. 30. Lyon, International Agency for Research on Cancer, 1980, pp. 571-577. WHITWELL, F., NEWHOUSE, M.L., BENNETT, D.R. A study of the histological cell types of lung cancer in workers suffering from asbestosis in the United Kingdom. British Journal of Industrial Medicrne 31(4):298-303, October 1974. WOODWORTH, C.D., MOSSMAN, B.T., CRAIGHEAD, J.E. Squamous metaplasia of the respiratory tract: Possible pathogenic role in asbestos-associated bronchogenic carcinoma. Laboratoq Investigation 48(5):578-584, May 1983a. 282 WOODWORTH, CD., MOSSMAN, B.T., CRAIGHEAD, J.E. Induction of squamous metaplasia in organ cultures of hamster trachea by naturally occurring and synthetic fibers. Cancer Research 43(10):4906-4912, October 1983b. WOOLCOCK, A.J., VINCENT, N.J., MACKLEM, P.T. Frequency dependence of compliance as a test for obstruction in the small airways. Journal of Clinical Znvesligation 48(6):1097-1106, June 1969. WRIGHT, J.L., CHURG, A. Morphology of small-airway lesions in patients with asbestos exposure. Human Pathology 1X1):68-74, January 1984. ZOLTAI, T., WYLIE, A.G. Definitions of asbestos-related mineralogical terminology. Annals of the New York Academy of Sciences 330:701-709, December 14, 1979. `283 CHAPTER 7 RESPIRATORY DISEASE IN COAL MINERS CONTENTS Introduction Prevalence of Smoking in Coal Miners Coal Workers' Pneumoconiosis Prevalence of Coal Workers' Pneumoconiosis Pulmonary Function Abnormalities in Simple and Complicated Coal Workers' Pneumoconiosis Relationship of Small Opacities to Emphysema and Airways Obstruction Lung Function in Subjects With Rounded or Regular Opacities Lung Function in Subjects With Irregular Opaci- ties Respiratory Symptoms and Exposure to Coal Dust Bronchitis and Dust Exposure Respiratory Mortality in Coal Miners Lung Function in Coal Miners Emphysema, Exposure to Coal Dust, and Cigarette Smoking Dust Exposure, Cigarette Smoking, and Ventilatory Function Summary and Conclusions References 287 Introduction An association between respiratory disease and coal mining has been recognized since the 16th century, when Agricola and Paracel- sus wrote of the diseases of miners (Hunter 1978). The first description of coal workers' pneumoconiosis (CWP! was given in the early 1800s by Laennec (Meiklejohn 1951) when he described cystic and noncystic melanotic masses in the lung, and in addition, melanotic parenchymal infiltrates in the lung. The melanotic masses were almost certainly progressive massive fibrosis (PMF) and the black infiltrates, simple CWP. It is clear from Laennec's description that he recognized an association between coal mining and the deposition of "la matiere noire pulmonaire." An excellent history of coal miners' lung disease in Great Britain can be found in a series of articles by Meiklejohn (1951, 1952a, 195213). Over the years, a large number of names have been attached to the conditions that affect the lungs of coal miners. Many early physi- cians assumed that there was a single respiratory condition arising from coal dust exposure, which was variously referred to as spurious melanosis, miners' asthma, anthracosis, miners' phthisis, and silico- sis. With the passage of time, it became evident that, aside from the lung diseases that commonly affect the general population, coal miners are prone to develop occupationally related lung diseases, namely coal workers' pneumoconiosis, silicosis, and chronic bronchi- tis (Morgan and Lapp 1976). Silicosis is covered elsewhere in this Report; therefore this chapter discusses coal workers' pneumoco- niosis and chronic bronchitis. The paramount importance of exposure to coal dust in the development of CWP is generally accepted, and complicated CWP is clearly associated with significant and often disabling chronic airflow limitation as well as with other respiratory impairments (Morgan and Seaton 1984; Morgan and Lapp 1976). Less certain is the magnitude of the role of coal mine dust as a cause or contributory factor in the development of bronchitis and emphyse- ma. The effects of long-continued inhalation of coal and other dusts are currently of major interest to epidemiologists and to those practicing occupational medicine. Clearly the results of the studies designed to characterize the effects of coal dust on lung function are of vital importance to officials concerned with compensation for occupationally related pulmonary disability. In these studies it is important to evaluate as potentially independent effects the role of coal dust in producing radiologic CWP and the role of coal dust in producing physiologic airflow obstruction (Weeks and Wagner 1986). This separation of the radiologic and physiologic responses to coal dust is even more critical when considering the effects of combined exposure to coal dust and cigarette smoke. 289 The respective contributions of cigarette smoking, dust exposure, and other environmental and occupational factors in the develop- ment of respiratory impairment in coal miners are examined in this chapter by reviewing the evidence currently available from mortali- ty and morbidity studies of coal miners compared with appropriate reference populations and the evidence on the frequency and extent of pulmonary impairment in coal miners. The roles of dust, cigarette smoking, and various confounding factors are taken into account and apportioned where possible. At the present time, there are approximately 150,000 underground coal miners in the United States. Ten years ago, the figure was about 170,000, but the closure of a number of mines in Appalachia has reduced the number of employed underground miners, In addition, 60,000 to 70,000 workers are employed in open cast or surface mines, but this number is constantly changing. Exposure to coal mine dust is greater in those employed underground; miners working at the face or in transportation are the most heavily exposed. Miners employed underground on maintenance and other activities are less exposed, and surface miners are the least exposed (Doyle 19701. Prevalence of Smoking in Coal Miners The prevalence of smoking for various populations of miners in different countries and during different time periods is presented in Table 1. In general, the prevalence of smoking among U.S. coal miners is currently similar to, or slightly higher than, the rates in the overall U.S. male population. However, coal mining as an occupation introduces a distortion in the pattern of smoking because of the prohibition against smoking while in the mine. As a result, the entire consumption of cigarettes by miners is limited to those periods when they are not underground; for a given number of cigarettes smoked per day, the pattern among miners would consist of periods of more intense smoking interspersed with long periods of not smoking (i.e., during working hours), in contrast to the more even consumption of cigarettes throughout the day that characterizes most cigarette smokers. Coal Workers' Pneumoconiosis Coal workers' pneumoconiosis (CWP) is defined as the deposition of coal mine dust in the lungs and the reaction of tissue to its presence (Morgan and Seaton 1984). However, the term is commonly applied only to the chest roentgenographic changes produced by coal dust, and the other tissue responses to coal dust are classified by their symptomatic, physiologic, or pathologic manifestations (e.g., chronic bronchitis, airflow obstruction, or emphysema). The radiologic 290 TABLE l.-Smoking characteristics of coal workers Study Higgins et al. (1968) Number and type of population 755 mining town residents. Great Britain Smoking characteristics (percent) SM NSIEX 15 25 Cammenta Tokuhata et al. (1970) 801 anthracite coal miners, Pennsylvania Ashford et al. ( 1970) 30.@30 underground and surface workers. Great Britain SM NS EX 78.7 15.3 6 Rae et al. 3,379 workers, 20 SM NS (1971) colleries. Great Britain 19.2 208 Large colleries Age 140 40-49 250 Independent Age <40 40-49 250 64.1 15.9 74.0 26.0 71.6 28.4 76.4 23.6 60.5 19.5 71.3 22.7 Ex-smokers not differentiated from smokers SWIG and Pelaic 119711 Lignite and brown coal miners, Yugoslavia SM NS EX 64.7 23.6 11.7 M TABLE k-Continued Study Number and type of population Smoking characteristics (percent1 Comments Mlnette (1972) 204 cd miners, Belgium SM 70.6 NS' 29.4 o Nonsmokers include smoken who did not inhale Phelpe (1972) 256 miners, U.S. Rocky Mountain region SM 65.6 Skrabski-Kopp et al. (1972) 1,066 coal miners, Hungary SM 75.6 Lowe and Khosla (1972) 3.012 excoal miners, 9,361 controls, Great Britain Ex-miners 86.6 Controls 80.7 NS 34.3 NSIEX 24.4 KibdstiE et al. (1973) Bituminous coal miners. United States SM NS 50.8 25.4 Ortmeyer et al. Coal miners and ex-miners, Coal miners, 60.9 19.7 (1974) Appalachia Ex-miners 47.1 52.3 EX 23.8 19.4 2039year-old miners smoked at a rate above 65% Fairman et al. (1977) 987 surface coal miners, six U.S. states 70.7 29.3 TABLE l.-Continued Study Number and type of population Smoking characteristica (percent) Comments Armstrong et al. Cod and gold miners, (1979) Australia Szymaykiewia (1979) Miners, Poland Potkonjak 970 cd nunera, 536 (1979) controls with no dust exposure Cochrane and Moore Coal miners, Great Britain (1960) Ram et al. 242 active and retired (1981) miners, Utah Love and Miller 1,677 colliery workers, (1982) Great Britain Cod miners Gold miners Miners Controls Age 2x34 SM/cigs 1-14 b 14 Age 55-64 SM/cigs 1-14 `-a 14 54 52.1 NSIEX 24.3 Pipe only 3.6 16 SM NWEX 56.7 41.3 66.3 33.7 13.7 46 47.9 SM 71.3 32 39.3 60 32 2a SM NS EX 38 23.6 36.4 SM NS EX 66.1 12.8 4.5 16.5% were intermittent smokers NCYIIC SM=Smoker; EX=Exsmoker: NS=Nonsmoker. manifestations of CWP are classified into two forms: simple, and complicated (often known as progressive massive fibrosis, PMF). Simple CWP is a reaction solely to the inhalation of coal dust. Although the efficiency and integrity of the lung defenses are important factors in the development of disease, cumulative dust exposure is of paramount importance. Characteristically, after a period of exposure, i.e., 10 to 15 years, small rounded opacities begin to appear in the upper lung fields of some miners. With continued exposure, they gradually spread to the middle and lower zones, and the increasing profusion of these opacities is used to categorize simple CWP on a 0 to 3 scale. The opacities are indistinguishable from those seen in silicosis. Simple CWP does not progress in the absence of further exposure. Moreover, increasing category of simple CWP is not associated with a decrement in ventilatory capacity (Cochrane et al. 1961; Gilson and Hugh-Jones 1955; Morgan et al. 1974). Complicated CWP is defined as the presence of an opacity greater than 1 cm in diameter on the chest radiograph of a subject who already has simple CWP (IL0 19801, and the volume of lung occupied by the large opacities on the radiograph is used to categorize complicated CWP into category A, B, or C. For the most part, complicated CWP develops on a background of category 2 or category 3 simple CWP. Necessary for its development is the presence of a fairly high dust burden in the lungs, plus some other factor or factors as yet not fully recognized or understood. Prevalence of Coal Workers' Pneumoconiosis In 1969 the National Coal Study was commenced by the National Institute for Occupational Safety and Health (NIOSH) (Morgan et al. 1972). Selected for study were workers at 31 coal mines, of which 2 were anthracite and 29 were bituminous. In the initial survey, an overall CWP prevalence of nearly 30 percent was found; 2.5 percent had PMF. A decreasing prevalence was noted from east to west, and there was a clear-cut relationship between the years spent under- ground and radiographic category. The disease was much more common in workers at the face than in surface workers. The prevalence of CWP in this study was undoubtedly overestimated, however. Part of the reason was that the early films were interpre- ted according to the 1958 International Labour Office (ILO) classifi- cation. In addition, some of the readers were inexperienced and tended to overread. The second round of the National Coal Study revealed a prevalence of 8 percent; the findings at the third round were just under 5 percent, with 3.85 percent having category 1; 0.48 percent, category 2; 0.04 percent, category 3; and 0.17 percent, PMF. The decline in the prevalence of pneumoconiosis noted between the first and third rounds of the National Coal Study is partly 294 accounted for by the use of different readers, partly by more stringent reading criteria, partly from the use of the IL0 standard films as yardsticks, and partly from improved coal dust control. An exodus of workers with higher categories of disease between the first and subsequent accumulations of subjects with radiographic evi- dence of pneumoconiosis also played a role, since those with CWP qualified for compensation. Both simple CWP and PMF are related to cumulative lifetime exposure to coal dust. The reduction or elimination of category 2 and category 3 simple CWP through effective dust control not only is possible but is rapidly being achieved in the United States and Great Britain (Jacobsen 1980). Since complicated pneumoconiosis develops almost entirely in subjects who have the higher categories of simple CWP (i.e., those with a high dust burden), the effective prevention of category 2 and category 3 simple CWP should almost completely eliminate PMF as well. The removal from further coal dust exposure of miners with early categories of simple CWP should also aid in reducing the incidence of PMF. Pulmonary Function Abnormalities in Simple and Complicated Coal Workers' Pneumoconiosis The radiologic changes of simple CWP are associated with the development of certain relatively minor pulmonary impairments. These include an increased alveolar-arterial gradient for oxygen, abnormalities of the distribution of inspired gas, and a modest increase in lung volumes (Morgan and Lapp 1976). The increase in lung volumes is a consequence of the focal emphysema that is an integral part of the pathology found with simple CWP (Morgan and Seaton 19841. Complicated pneumoconiosis is associated with a reduction in lung volume and diffusing capacity, ventilation perfusion mismatching, an obliteration and destruction of the pulmonary vascular bed that leads to nonhypoxic pulmonary hypertension and car pulmonale, and with the presence of generalized airways obstruction (Gilson and Hugh-Jones and Seaton 1955; Lyons et al. and Seaton 1981; Morgan and Seaton 19841. Relationship of Small Opacities to Emphysema and Airways Obstruction The small opacities present in the lung in the various pneumocon- ioses can be classified as either rounded (regular) or irregular. Small rounded opacities have a fairly rounded and regular margin. They are classified according to their size into p, q, and r types: p is up to 1.5 mm in diameter, q is between 1.5 and 3 mm, and r is between 3 and 10 mm. Usually only one type of opacity is present, 295 but mixtures are occasionally found in the same lung. The reading of the film should be based on the predominant opacity noted. Irregular opacities are also classified according to size: s opacities are up to 1.5 mm in width, t opacities are between 1.5 and 3 mm wide, and u opacities are between 3 and 10 mm. Irregular opaciti,s are characteristically seen in asbestosis. In some smokers scanty irregular opacities may be observed. Rounded and irregular opacities occasionally occur together, usually in a person who has experienced various exposures or in a person with either silicosis or coal workers' pneumoconiosis who also is a heavy smoker. Lung Function in Subjects With Rounded or Regular Opacities A number of investigations have shown that the p, or punctate, type of opacity seen in simple CWP is associated with a reduced diffusing capacity (Sartorelli et al. 1963; Lyons et al. 1967; Seaton et al. 1972; Musk et al. 1981). In addition, an increased parenchymal air space size has also been observed in subjects with a p type of opacity (Hankinson et al. 1979). No detectable difference in lung function between subjects with the p, q, or r type of opacity was observed in this study. These physiological changes have also been demonstrated in nonsmoking miners with simple CWP (Hankinson et al. 1979; Seaton et al. 1972). The indices of lung function that were tested in the miners with the p and q opacities were similar (Hankinson et al. 1979) except for the diffusing capacity, which was significantly lower in those with the p type of lesion (Seaton et al. 1972). Static compliance was reduced marginally, but not significantly, with the q type of opacity. The type of opacity was not significantly related to differences in dynamic compliance at increased rates of breathing (Seaton et al. 19721. Musk and colleagues (1981) examined the lung function in 125 coal miners identified in 1968 as having the simple pneumoconiosis of coal workers and reexamined 9 years later. Pulmonary function was related to both smoking history and coal dust exposure. Miners who smoked in 1978 had lower forced expiratory volume in 1 second (FEVJ, forced vital capacity (FVC), and FEV,/FVC ratio and a higher ratio of residual volume to total lung capacity (RV/TLC) compared with nonsmokers. Ex-smokers had a lower carbon monox- ide diffusing capacity (DLCO) than nonsmokers. Total dust exposure was inversely related to FVC and lung elastic recoil at TLC. After correcting for the effects of age, height, and smoking category, miners whose radiographs showed predominantly p and r types of opacities had a reduced DLCO when compared with miners with the q type of opacity. In the researchers' experience, irregular opacities were also associated with a reduced DLCO, and were thought to 296 reflect the presence of both emphysema and diffuse fibrosis. In addition, the r type of opacity, but not the p type, was associated with reduced maximal recoil at TLC, and reduced recoil at 50 percent of TLC and at 1 L below TLC, and with an increased RV and RV/TLC percent compared with miners with the q type of opacity. The decreased compliance in subjects with the r type of opacities noted by Musk and colleagues (1981) may be a consequence of the exposure of some of these subjects to silica. Irregular opacities were not associated with increased obstruction or with smoking; here the results of Musk and colleagues differ from almost all other studies. Lung Function in Subjects With Irregular Opacities The significance of irregular opacities in the lungs of coal miners has been the subject of a number of investigations. Lyons and colleagues (1974) pointed out that there was a positive association between the presence of irregular opacities and emphysema and impairment of FEV,. Unfortunately, this was a post-mortem study in which no smoking histories were available. Subsequently, Aman- dus and colleagues (1976) investigated the significance of irregular opacities in the lungs of 6,166 working U.S. coal miners for whom complete smoking histories were available. Irregular opacities on the chest radiographs were shown to be associated with smoking, bronchitis, age, and years worked underground. Smoking was not associated with the presence of regular opacities. Although irregular opacities were observed in nonsmokers, they were 2.5 times more common in those who smoked. Among nonsmoking miners, there were no significant differences in the lung volumes or flow rates of the men with normal chest x rays, irregular opacities, rounded opacities, or mixed opacities. Smokers had similar FVCs in each of the radiologic categories when compared with nonsmokers, but FEV, and FEV,/FVC were lower and RV and TLC were higher. In addition, smokers with irregular opacities had a lower FEV, and a higher RV and TLC than smokers with normal chest x rays or rounded opacities. A study by Cockroft, Berry, and colleagues (1982) of coal workers and ex-workers showed that irregular opacities were related to age, smoking, and underground exposure in those receiv- ing disability benefits. Cockcroft, Seal, and colleagues (1982) examined the relationships among lung function tests, irregular opacities on chest radiograph, and the pathologic changes of emphysema in 46 men who had been referred for lung function tests during life and who had died between 1970 and 1979. Irregular opacities on radiograph were associated with a reduced DLCO and reduced TLC, an increased pathologic score for emphysema, and to a lesser extent, an increased pathologic score for fibrosis. Smoking histories were obtained in all but five of these workers, and there was no association of smoking with any 297 157-964 0 - 86 - 11 particular lung function or pathologic finding. However, almost all of the subjects in the study were current smokers (two were nonsmokers and two were former smokers), which limited the ability of the study to examine the effects of smoking. The majority of the evidence indicates that simple CWP is associated with mild overdistension or hyperinflation of the lungs. There is some evidence, especially in miners with the p type of opacity. that there is also a reduction in DLCO. The decreased DLCO does not appear to be associated with increasing airways obstruction, but with focal dust emphysema. The available data indicate that cigarette smoking plays a much greater role in reducing DLCO than does the presence of simple CWP (Frans et al. 1975). Irregular opacities occur occasionally in the lungs of coal miners and former miners. For the most part, they are associated with smoking, age, bronchitis, and years spent underground. Bronchitis may be the common denominator in the production of irregular opacities, and the increased prevalence of bronchitis in smoking coal miners may be the reason for the increased prevalence of irregular opacities found among smokers in some studies. Irregular opacities are seen in nonoccupationally exposed groups (Carilli et al. 1973), in subjects exposed to silica, in asbestos miners and millers (Morgan 1978), in workers who manufacture manmade fibers (Weill et al. 1983), and in workers with other conditions, suggesting that irregu- lar opacities may be a nonspecific response associated with the presence of bronchitis, regardless of its etiology. Respiratory Symptoms and Exposure to Coal Dust The relationship between dust exposure and bronchitis was noted by Thackrah (1832) and Greenhow (1860) in the 19th century. Although these pioneer workers noted a higher prevalence of bronchitis and other respiratory ailments in the dusty trades as a whole, they particularly emphasized the importance of textile dust as a cause of bronchitis. Until recently the use of the terms "chronic bronchitis" and "emphysema" implied that these two conditions were invariably associated and that both, for the most part, were related to cigarette smoking. In this context, "bronchitis" implied a condition character- ized by cough and sputum, usually associated with a reduction in ventilatory capacity or frequently leading to one (Fletcher et al. 1959). Subjects with these symptoms who also had concomitant chronic airflow obstruction were usually diagnosed as having chronic bronchitis and emphysema, assuming from the association of the two diseases that they were part of the same process. At the time the committee appointed by the Medical Research Council (MRC) of Great Britain published its statement (British Medical Journal 298 1966), it was known that not all subjects with chronic bronchitis showed an associated reduction of FEV1, but the committee did not elaborate fully on the implications of the term "bronchitis." It was assumed, moreover, that there was a relationship between the symptoms of cough and sputum and a decreased ventilatory capaci- ty, and that sooner or later most or all subjects with chronic bronchitis would develop some degree of irreversible airways ob- struction. The MRC's (1965) division of bronchitis into obstructive bronchitis and simple bronchitis, a condition characterized by the presence of cough and sputum in the absence of airways obstruction, was the first step taken toward a better understanding of the implications of a diagnosis of bronchitis. Subsequently, the general use of the MRC questionnaire on chronic bronchitis for symptoms without reference to lung function led to an appreciation of the pathophysiology of this condition (MRC 1965), and the pathological features of bronchitis as described by Reid (1960) in her studies provided a means of quantitating the severity of the condition. Bronchitis and Dust Exposure Many of the studies showing an association between dust exposure and an increased prevalence of chronic bronchitis have been carried out with coal miners. Coal miners represent a clearly defined and relatively large group of subjects who seldom change their occupa- tion, and thus present an ideal study population. Ashford and colleagues (1970) showed that the prevalence of cough and sputum increased with age and, it may be inferred, with cumulative dust exposure. Shortly thereafter, Rae and colleagues (1971) demon- strated a relationship to dust exposure. Kibelstis and colleagues (1973) showed, in a U.S. population of more than 9,000 working coal miners, that cough and sputum were related to dust exposure and also to cigarette smoking. When only nonsmokers were considered, there was a gradient in the prevalence of bronchitis from the least to the most dusty jobs. This occurred independent of age. In smokers, the effect of cigarette smoking almost completely overwhelmed the effects of dust and age, at least as far as symptoms were concerned. Similar findings have been reported in Belgian coal miners (Minette 1976; Vuylsteek and Depoorter 1978). The effect of dust and cigarette smoke on bronchial gland dimensions in coal miners has recently been investigated (Douglas et al. 1982). These investigators demonstrated that both dust and cigarette smoking had an effect on the Reid index and that they led to mucous gland hypertrophy. There is thus a fairly widespread acceptance that the long-continued inhalation of coal dust and other dusts may lead to an increased prevalence of cough and sputum in the absence of cigarette smoking. Moreover, it has been demon- strated that the prevalence of dust-induced bronchitis is related to cumulative dust exposure (Rogan et al. 1973; Kibelstis et al. 1973). The topic of industrial bronchitis is more fully discussed in another chapter of this Report, but the data suggest that there is an independent and additive effect of coal dust exposure and cigarette smoking on the prevalence of chronic bronchitis. Respiratory Mortality in Coal Miners Early mortality data of coal miners showed a high death rate from respiratory disease. This was true for both Great Britain (Registrar General 1958) and the United States (Enterline 1964; Guralnick 1963). Although there may be some doubt as to the precise accuracy of such data, it is probably true that there was an increased standardized mortality ratio (SMR) for respiratory disease among coal miners. There was, however, little convincing evidence to establish that coal dust was a major causative factor in this increase. Tuberculosis, emphysema, and bronchiectasis were more common in coal miners, and most of the increased mortality could be explained by an increased prevalence of these diseases. In addition, Enterline (1964, 1972) had shown in a series of retrospective analyses that the SMR for coal miners as a group was elevated, but a substantial portion of the excess was a consequence of trauma and accidents. When deaths due to these excesses were excluded, excess mortality still persisted. Much of the excess was due to respiratory disease, and although the death rate for chronic bronchitis and emphysema was reported to be increased, so also were the death rates for tuberculosis and lung cancer. While it is easy to postulate a relationship between occupation and bronchitis, it is also clear that bronchitis and lung cancer have a common causative agent, namely cigarette smoke. In addition, coal miners, particularly in the United States, constituted a distinctly underprivileged group during the early part of this century, and as such suffered from overcrowding and poor medical care, both of which contributed significantly to a higher death rate from bronchiectasis and tuberculosis and other infectious diseases. Over the past two decades, a number of well-controlled epidemio- logical studies of morbidity and mortality of coal miners have been carried out in both Great Britain and the United States. Liddell (1973a) looked at the frequency of time off from work because of illness in a cohort of 29,084 men. He showed that miners spent more time off work than nonminers. The highest rate of incapacity was present in the lowest paid workers; this applied as much to coal face miners as to surface workers. Pneumoconiosis was associated with greater time off work. An additional investigation of the mortality of 5,362 British miners who died in 1961 showed that they had higher death rates for accidents and pneumoconiosis than the general population, but lower death rates for cancer in general and for lung 300