Document NeLm80538G52b1a3GD33KKyvQ

Poster Session I CARBORUNDUM PNEUMOCONIOSIS R. BEGIN, M.D. A. Dufresne, Ph.D. A. Cantin, M.D. Masse, M.D. P. Sebastien, Ph.D. P. Durand, Ph.D. G. Perrault, Ph.D. Universite de Sherbrooke, Sherbrooke (QC), Dust Disease Unit, McGill School of Occupational Health, Montreal (QC) and Institut de Recherche en Sante et Securite' au Travail, Montreal (QC) INTRODUCTION Silicon carbide (SiC) also called carborundum is a universal ly used abrasive produced by die fusion of high-grade silica and finely ground carbon in electric furnace at 2400C. A re cent review of the subject in Parkes textbook6 led to the con clusion that there was no evidence that exposure to silicon car bide dust gave rise to a pneumoconiosis. Nonetheless, pneumoconiosis has been reported in long term workers engaged in die manufacturing of SiC and it was suspected that sick workers had been previously exposed to other dust hazards or to quartz dust in the raw materials of the manufactures. One pathological report raised the possibili ty of a carborundum pneumoconiosis.4 Recent investigations in the Quebec carborundum industry have documented an excess of radiographic abnormalities compatible with pneumoconiosis, particularly in older workers of the industry.7 In view of these findings, col laboration with die industry was established and a thorough multidisciplinary investigation was initiated. Pathological studies of available lung tissue from long term workers of the SiC industry were analyzed in detail.5 Recent chest radiographs of 1984 and 1979 of some 128 workers were reviewed.3 Evaluation of occupational exposures in the in dustry was conducted and reported in detail.li2 A review of the occupational hygiene led to the preparation and characterization of reference samples of respirable particles collected in the SiC production industry for use in this ex perimental research. The objectives ofthis study were to evaluate the in vivo lung biologic activity of the mineral dusts found in the carborun dum manufacturing industry, to identify the offending dust in order to establish appropriate control of dust level in the workplace. MATERIALS AND METHODS Experimental Design Seventy-two sheep were used in this study. The flock was divided into 9 groups of 8 sheep. Following pre-exposure (control) studies, the sheep tracheal lobe was exposed to: 100 ml saline = Sa group (control); 100 mg latex beads in 100 ml saline = latex group; 100 mg graphite in 100 ml saline = graphite group; 100 mg SiC raw particles in 100 ml saline -- SiCp group; 100 mg SiC ashed particles in 100 ml saline = SiCpa group; 100 mg Minusil-5 in 100 ml saline = Si group; 100 mg crocidolite fibers in 100 ml saline -- Cro group; 100 mg SiC raw fibers in 100 ml saline = SiCf group; 100 mg SiC ashed fibers in 100 ml saline = SiCfa group. Exposure to the tracheal lobe was carried out via bronchoscopic infusion ofthe suspension in the lobe. The animals were studied prior to exposure and post-exposure at month 2, 4, 6, and 8 by BAL and by histopathological methods at month 8. The Minerals The materials for exposure were obtained from the follow ing sources: Latex beads from Sigma Chemical Co., St-Louis, MO; these particles are uniform in size with a mean diameter of 1 p. Minusil-5 from Pennsylvania Glass Co., Pittsburgh, PA; the silica particles are well characterized with 99.9% of diameter < 5 jt,and 95% < 1 p. Crocidolite fibers from the Union Internationale Contre le Cancer (UICC); these fibers have a known diameter of0.17 .01 p with an average length of 3.9 0.2 ji95% of fibers with a length < 10 p, 82% < $P All other samples were obtained from the Quebec SiC in dustry, prepared and characterized. Briefly, these materials were collected from the production sites in the Acheson fur naces of two Quebec SiC plants. The non-fibrous SiC was col lected from the center of large lumps of produced materials. The SiC fibers were collected mainly from the outside part of the main cylindrical lump produced by the process. The graphite was extracted from the core of a fired Acheson fur nace. The raw particulate and fibrous SiC were, as expected, contaminated with graphite flakes on surface, which at least in theory, could alter biological activity. To eliminate these contaminants, reference samples offibrous and particulate SiC were ashed. Graphite particles were 98.8% < 5 p, particulate SiC raw or ashed were 99.5% <5 p. For the SiC fibers, seventy percent offibers were less than 5 p, with some longer than 20 p. The fibrous SiC raw or ashed were of an average of 0.27 p 0.27 diameter with an average length of 6.8 11.2 p. These morphometric data were considered in the 1193 Poster Session I selection ofthe asbestos fiber crocidolite, for comparison in these experiments. Assessment of Lung Reaction To evaluate the disease process induced by exposure to these respirable minerals, we looked at lung lavage cellularity and biochemistry as biologic indicators ofalveolitis. The severi ty oflung tissue damage was evaluated at autopsy, 8 months after exposure, by histopathology. To assess interstitial lung matrix changes we looked at the glycosaminoglycan ac cumulation in BAL fluid. We also measured the production of fibronectin by BAL cells in culture. Lung lavage fluid was analyzed for the presence ofmolecules capable of enhancing fibroblast proliferation. Histopathology At month 8 ofthe study, all sheep were sacrificedand the hmgs removed from the chest cavity. The tracheal lobe was iden tified and 9 samples ofdie lobe ofeach sheep were obtained each time for microscopic examination. RESULTS The Particulates In comparison to Sa group, all the particulate exposed groups had a slight and transient early increase in cellularity except for die Si group, which had an early 500% increase in cellularity which decreased to250% at month 4, but remained elevated to the end of experiment. This was largely due to increase in die macrophage population, but increases in lym phocytes and neutrophils were also significant and sustained in the Si group. Similarly, in die biochemical and cell culture analyses, only the Si group had significant increases in BAL lactate dehydrogenase, glycosaminoglycan, and increased production of fibronectin and fibroblast growth activity. The lung morphology of the sheep was normal in groups Sa and latex. The hmg tissue ofsheep in the graphite group, SiCpand SiCpa groups contained accumulation ofparticles in alveoli and interstitium without cellular reaction. In die graphite ex posed sheep, the morphologic changes are reminescent ofthe early simple pneumoconiosis ofcoal workers.6 In die Si ex posed sheep, the lung changes are characterized by a diffuse alveolitis with early nodular silicotic lesions as reported in our earlier studies. The pathological scores were 0 0 for Sa group, latex group, graphite group, SiCp group and 2.9 1.0 for die Si group (p < 0.01 for Si group vs others). The Fibers Briefly, cellularity of BAL was increased in all die fiber groups following exposure with a larger attenuation for die SiCfgroup. This effect was pancellular and was also seen in the pattern of response of LDH overtime. Fibronectin pro duction was significantly increased, again with some attenua tion for die SiCf group. Fibroblast growth activity was in creased significantly in all fiber groups. Pathologic analysis of lung tissue in the crocidolite exposed sheep revealed a peribronchiolar fibrosing alveolitis as previously reported in other asbestos exposure. In die fibrous carborundum exposed sheep, we found nodular lesions in the parenchyma which were not located around the bronchioles. These nodules were composed of multinucleated macro phages, monocytes and a few neutrophils and contained several carborundum fibers and "bodies.*' The intensity and profusion oflesions in the fiber groups were: 1.9 0.25 for Cro group, 1.2 0.21 for the SiCf and 1.6 0.2 for die SiCfa group (p > 0.05 between die 3). The slightly lower score (p > 0.05) in die SiCf compared to SiCfa could sug gest a partial inhibitory effect ofthe graphite on surface ofthe SiCf fibers. DISCUSSION Id recent years, several epidemiological and clinical investiga tions have suggested that carborundum workers may have a specific occupational lung disease. This experimental study of the airborne dust particles and fibers in die carborundum industry provides significant new information on the pathogenesis ofinterstitial lung disease in workers ofthat in dustry. It documents that of all the non-fibrous particulate minerals encountered on rite, only silica appears to be poten tially responsible for some ofthe lung injury, hi addition, this study documents clearly that fibrous SiC has significant biologic activity and can initiate a fibrosing lung disease. In SiC manufactures, SiC fiber inhalation can contribute to the genesis of an interstitial lung disease. Therefore, it is ap propriate to recommend that surveillance ofthe work environ ment in that industry should include an assessment ofairborne fiber levels. REFERENCES 1. Dufresoe, A., Lesage, J., Ferrauh, G.: Evaluation ofOccupational Ex posureto Mixed Dusts and Polycyclic Aromatic Hydrocarbons inSilicon Carbide Plants. Am bid Hyg. Assoc. J. 48:160-166 (1987). 2. Dufresne,A.,Pemuh,G.>Sebastien,P.,Adnot,A.,Baril,M.:Morpbology and Surface Characteristics of Particulates from Silicon Car bide Industries. Am bid Hyg. Assoc. J. 49: in press (1988). 3. Durand, P., Begin, R., Samson, L.,Canlin, A., Masse, $., Dufresoe, A., Renault, G., Laflamme, J.: SiliconCarbkfe Pneumoconiosis: Current ExposureLevels do not Changethe Radiographic AssessmemofDisease. Submitted for publication, 1988. 4. ftmahashi, A , Schhieter, D.P., Pirrtar, K., Siegesmumi, K.A., Manddr G.S., Mandel, N.S.: Pneumoconiosis in Workers Exposed to Silicon Carbide. Am Rev. Respir. Dis. 129:635-640 (1984). 5. Masse, S., Begin, R., Cantin, A.: Pathology of Silicon Carbide Pneumoconiosis. Modem Pathology 1:104-108 (1988). 6. Parkes, W.R.: Occupational Lung Disease, 2nd Ed. Butterworth, Lon don, U.K. (1982). 7. Peters, J.M., Smith, TJ., Bernstein, L., Wright, W.E., Hammond, S t: Pulmonary Effect nfErpnaires in Silicon Carbide Manufamrring. Br. J. bid. Med 41:109-115 (1984). 1194 Poster Session l IMAGING THE PNEUMOCONIOSES IN 1988: A MULTIDISCIPLINARY APPROACH R. BEGIN, M.D. S. Masse, M.D. A. Cantin, M.D. G. Bisson, M.D. D. Bergeron, M.D. Centre Hospitalier Universitaire, Sherbrooke, Quebec, Canada J1H 5N4 INTRODUCTION In recent years, it has become increasingly clear, on die basis ofhuman and experimental data, that lung fibrosis associated with mineral dust inhalation was the end-stage phenomenon ofa long chronic inflammatory process initiated by die reten tion ofbiologically active mineral particles in the lung tissue. The early stages oflung tissue reaction to mineral dust deposi tion is characterized by an excessive accumulation and activa tion ofmacrophages in the peripheral bronchoalveolar tissue. This is well documented both in animal studies9 and in humans.4'3'16 Asbestos dust inhalation produces the fun damental early lesion ofasbestosis the peribronchiolar fibros ing alveolitis; quartz dust inhalation produces the more nodular, often perivascular accumulation ofmacrophages and lymphocytes in the alveolar spaces of lung tissue. As these mineral dust diseases progress, they are associated with extension ofdie process to the adjacent alveolar and in terstitial lung tissues which leads to diffuse interstitial lung fibrosis. However, we know now that this process can be limited to its early peribronchiolar reaction and leave the lung tissue nearly intact. This is particularly die case for asbestosinduced lung disease, hi silica-induced lung disease,11 after the initial nodular lesion, the process becomes less inflam matory, fibroblasts accumulate in the nodules with excessive deposition of reticulin and collagen in and between the cells in die nodule, and eventually the fibrotic collagenous process aggregates the individual nodules to form masses of fibrotic tissue. Knowing these fundamental pathological processes, strategies to detect these diseases at an early inflammatory stage have been developed. MODES OF DETECTION Rales The observation ofbilateral basilar end-inspiratory in asbestos workers with or without asbestosis suggest that auscultatory rales are found in most workers with asbestosis; their profu sion correlates fairly radiographic and functional parameters of severity of asbestosis.3 However, rales are die initial find ing ofdisease in asbestos workers in less than 5 % ofcases and when present, they likely reflect a fibrotic process already in place. In quartz exposed workers, rales are usually absent and of limited interest in detection of silicosis. Chest Radiograph The standard PA high kilovoltage chest radiograph is die definite indicator of die mineral dust pneumoconiosis and its value has been well established for die detection of both asbestosis and silicosis. However, it has been documented that the chest radiograph can be normal in up to 10% of symp tomatic patients with proven interstitial lung disease. In asbestosis, we have documented similar findings,3*3 and in silicosis substantial pathological changes in the lung tissues have been observed in stone cutters with normal chest radiograph.11 Thus, whereas chest radiograph is a useful mode of detection of disease, cannot be considered as a sen sitive indicator of early disease. Computed Tomograph of the Thorax In asbestos related pleuropulmonary diseases, earlier clinical studies13,14 on relatively small populations of patients have found that the CT scan was significantly more sensitive than conventional chest X-rays in die detection ofdisease. We ob tained a CT scan of die thorax in 127 long term asbestos workers who were also evaluated by conventional posteroanterior (PA), lateral and obliques (4-view) X-rays, and clinical and functional evaluations.2 Our analysis of the total scores ofdie pleuropulmonary changes and profusion of parenchymal opacities shows that the three methods can detect about the same total amount of abnormalities in each subset of workers, which is at variance with previous clinical reports.13,14 Pleural plaques were scored slightly higher on the four-view films than on die PA film, in agreement with a previous report comparing these methods,13,14 but pleural plaques were scored significantly lower on die CT scan, most ly because of die lower yields at die costophrenic angles and diaphragms. The largest discrepancies between the three methods were observed in die evaluation ofpleural calcifica tions. On PA films, calcified pleural plaques were often suspected, but could be confirmed by one offoe other methods in only two ofnine cases. Offoe 27 definite pleural calcifica tions detected in our 127 asbestos workers, however, 14 were detected only by CT scan and all those detected by the PA and four-view films were also observed on foe CT scan. Our data on asbestos workers without sufficient criteria for asbestosis but with rigid P-V curve and increased Ga-67 lung uptake show that foe CT scan does not detect significantly more pleuropulmonary abnormalities than PA films. With both methods, workers with early asbestos alveolitis could not be separated from those without asbestos alveolitis or asbestosis. 1195 Poster Session / In 58 silica-exposed workers, we have also used computed tomography of the thorax.7 On the basis of chest radiograph, 6 were without silicosis, 30 had simple silicosis without coalescence or large opacity, 13 had silicosis with coalescence and 9 had silicosis with large opacity. In the presence ofsim ple silicosis without coalescence or large opacity cm plain chest film, CT scanning ofdie thorax revealed conglomerations in 10/30 cases, 70% of which could not be seen with the addi tion of lateral and oblique chest films. This additional infor mation on the presence ofconglomeration is particularly im portant as it identifies the presence of a complicated disease which could be either early coalescence of silicotic nodules, tuberculosis or other lung processes such as lung tumor. Fur ther investigations documented that ofdie 10 conglomerations detected by CT scan only, 2 were tuberculous lesions, 1 was a carcinoma and 7 were ofsilicotic origin. It has been reported in the last year dial the use ofultra-thin CT scan cuts (1-2 mm) may improve die imaging of interstitial reticular or nodular lung lesions. However, these clinical observations by others and ourself have not been scientifically validated. Gallium-67 Scan Ga-67 scanning has been used in clinical medicine for over 15 years in the detection of tumors and sites of occult infec tion, two disease processes associated with chronic inflam mation. The mechanisms of localization of the radionuclide in die inflammatory site, however, has been only partially clarified recentiy. After intravenous injection of the ra dionuclide, Ga-67 is rapidly bound to serum proteins, transfer rin, haptoglobin and albumin, and less than 1 % is transferred to the leucocytes. Gallium-67 lung uptake is primarily associated with activated macrophages producing excessive amount of fibronectin4 and to correlate with histopafoological scores of inflammation in lung tissue and with BAL levels of Ga-67 radioactivity retrieval.4 In asbestos workers ofthe mines and milk ofQuebec, we have obtained routinely Ga-67 scans in over 300 workers who can be divided into 4 categories: A = workers without asbestosis and normal scan, B -- workers without asbestosis and abnormal scan, C -- workers with asbestosis and abnormal scan, D = workers with asbestosis and normal scan. The workers in groups A and B have chest radiograph in the ILO categories 0/1 or 0/0 and they do not have bilateral rales on auscultation. Their lung volumes are within normal predic tion but some 66% ofthe workers in group B have increased rigidity of the lung pressure-volume curve and exercise in duced hypoxemia.311 On lung biopsy, they have a peribron chiolar macrophagic alveolitis. The workers in groups C and D have radiographic changes ofcategory > 1/0, the majori ty ofthem have bilateral rales and a restrictive pattern oflung function. What differentiates groups C and D is that workers with asbestosis in group C have increased Ga-67 lung uptake whereas those in group D have a normal scan. These dif ferences between groups A and B or C and D are not related to pleural disease,15 but relate best to the rate of foil of vital capacity; the workers with enhanced Ga-67 lung uptake have increased rates of decline of vital capacity per year. We have obtained computer-based quantitative analysis of Ga-67 uptake in a group of46 long term workers exposed to silica dust at work in foe granite industry or in foundry and in a group of 13, age, sex and smoking habit matched con trols. In foe controls, Ga-67 scan index averaged 1.77 0.46; in the 11 workers exposed to silica dust without silicosis, the index was 3.05 0.69. In 12 workers with simple silicosis 3.75 0.70; in 8 workers with silicosis and coalescence it was 7.25 2.23 and in 15 workers with large opacities it was 7.97 1.03. These data therefore confirm the work of Siemsen in documenting that Ga-67 lung uptake is enhanced in silicosis and document that in long term silica-exposed workers with or without simple silicosis, Ga-67 lung uptake is increased at 200% control value and when the disease becomes complicated tty coalescence and/or large opacity, the Ga-67 uptake is further enhanced to 400% control value. Bronchoalveolar Lavage In the interstitial lung disease which could be related to asbestos exposure, BAL analyses are of interest: 1) to eliminate other etiologies of lung injury, 2) to document asbestos exposure, 3) to support other clinical information, 4) to study the biological mechanisms. Following our initial report ofa substantial number of long term workers with ab normal Ga-67 scan in foe absence of other criteria for asbestosis,1 we have investigated several asbestos workers and similar studies were conducted by Dr. Rom at NIH. In these studies, it was documented that macrophages of foe bronchoalveolar space of asbestos exposed workers demonstrated marked structural changes, were producing ex cessive amount of fibronectin, fibroblast growth factor and increase /-interferon which could participate in the pathogenesis ofasbestosis. In our experimental studies in foe sheep model, we have fully reported similar evidences ofac tivated macrophages producing excessive amount of fibronec tin, fibroblast growth factor and neutrophil chemotactic fac tors. Thus, these data document that in support ofa diagnosis ofearly asbestosis (asbestos alveolitis), BAL analyses can pro vide additional information which pertains to several mechanistic features of disease activity. Among our silica workers presented in foe Ga-67 scan sec tion of this paper, we obtained BAL in 17. In foe workers without silicosis (group 2), our results demonstrated increases in total cellularity ( x 2), macrophage (x 2), lymphocyte (x 1.5), neutrophil (X 4), eosinophil (x 2), albumin(x 2.5)and immunoglobulin IgM (x 5), without increases in fibronec tin or procollagen. These data in silica exposed long term workers without overt silicosis are essentially in agreement with the data of Christman et al10 in documenting foe presence of a sub-clinical quartz alveolitis in these workers. In foe workers with simple silicosis, cellularity ofBAL is fur ther increased, particularly for lymphocytes (x 4 control), neutrophils ( X 8 control) but with BAL biochemical results comparable to those of group 2. In foe workers with com plicated silicosis (coalescence and/or large opacity), cellularity is also increased but, whereas albumin in BAL is now com parable to control, immunoglobulins IgG, IgA, IgM are foe 1196 highest, fibronectin and procollagen are highly increased (P < 0.05), which would agree with the current concepts of an activated fibrotic process. Of interest, we have also documented that when the disease was radiographically detec table, there was a significant increase in fibroblast growth fac tor which was observed even in the absence of coalescence and/or conglomeration.8 Pulmonary Function Tests In the evaluation ofearly disease in asbestos workers, several investigators have suggested that spirometry, diffusion and gas exchange studies could identify workers with asbestosis as well as chest radiograph. Futhermore, it has been documented by Jodoin et al,12 and confirmed in our own in vestigations that rigidity of the lung pressure-volume curve could be seen in several workers without radiograph changes.3 4 We have further documented that this finding was usually associated with enhanced gallium-67 lung uptake and when a lung biopsy was obtained, it showed the fun damental early macrophagic peribronchiolar alveolitis associated with early asbestosis. Also we found that early peribronchiolar disease did not significantly reduce the spirometric flow rates but caused a slight increase in upstream resistance only at low lung volumes.6 In silica-exposed workers, we have also obtained the usual lung function tests as well as pulmonary mechanics. This is the subject of distinct report. DISCUSSION Recent researches in the biology of the mineral dust pneumoconioses have substantially increased our understand ing of the sequence of events leading to fibrosis of die lung. Fibrosis in the mineral dust pneumoconioses is an end-stage result ofa chronic inflammatory process which is continuously activated by the chronic retention of the mineral particles in the lung tissue. In parallel, in-depth clinical investigations of mineral dust exposed workers with or without pneumoconiosis have identified workers without the classical findings of the pneumoconiosis but with significant abnormalities of CTscan, lung lavage, Ga-67 lung scan and lung pressure-volume curves similar to those of early disease in the animal studies. These abnormalities can detect the early inflammatory lesion of mineral dust pneumoconioses before its fibrotic stage. Newer approaches to prevent fibrosis of die lung tissue are currently under animal investigation in several laboratories. Poster Session I REFERENCES 1. Begin,R.,Cantin,A.,Drapeau,G.,Lamoureux, G.,Boctor,M.,Masse, S., Rola-Pleszczynski, M.: Pulmonary Uptake ofGallium-67 in Asbestos Exposed Human and Sheep. Am. Rev. Respir. Dis. 127:623-630 (1983). 2. Be'gin, R., Boctor, M., Bergeron, D., Cantin, A., Berthiaume, Y., Peloquin, S., Bisson, G., Lamoureux, G.: Radiographic Assessment of Pleuro-pulmonary Disease in Asbestos Workers: Postero-anterior, Four View Films and Computed Tomograms ofthe Thorax. Brit. J. Indust. Med. 41:373-383 (1984). 3. Be'gin, R., Cantin, A., Berthiaume, Y., Boileau, R., Bisson, G., Lamoureux, G., Rola-Pleszczynski, M., Drapeau, G., Masse, S.,BoctoT, M., Breault, J., Peloquin, S., Dalle, D.: Clinical Features to Stage the Alveolitis in Asbestos Workers. Am. J. Indust. Med. 8:521-536 (!985). 4. Begin, R., Bisson, G., Lambert, R., Cote, Y., Fabi, D., Martel, M., Lamoureux, G., Rola-Pleszczynski, M., Boctor, M., Dalle, D., Masse, S.: Gallium-67 Uptake in the Lung of Asbestos Exposed Sheep: Early Association with Enhanced Macrophage-derived Fibronectin Accumula tion. J. Nucl. Med. 27:538-544 (1986). 5. Begin, R., Martel, M., Desmarais, Y., Drapeau, G., Boileau, R., RolaPleszczynski, M., Masse, S.: Fibronectin and Procollagen in Levels in Lung Lavage of Asbestos Exposed Humans and Sheep. Chest 89:237-243 (1986). 6. Begin, R., Masse, S., Sebastien, P., Bosse, J., Rola-Pleszczynski, M., Boctor, M.,Cote, Y., Fabi, D., Dalle, D.: Asbestos Exposure and Reten tion as Determinants ofAirway Disease and the Asbestos Alveolitis. Am. Rev. Respir. Dis. 134:1176-1181 (1986). 7. Begin, R., Bergeron, D., Samson, L., Boctor, M., Cantin, A.: CT Assessment of Silicosis in Exposed Workers. Am. J. Roent. 148:509-14 (1987). 8. Begin, R., Cantin, A., Boileau, R., Bisson, G.: Spectrum ofthe Alveolitis in Quartz-exposed Humans. Chest 92:1061-1067 (1987). 9. Brody, A.R., Hill, L.H., Adkins, B., O'Connor, R.W.: Chrysotile Asbestos Inhalation in Rats: Deposition Pattern and Reaction ofAlveolar Epithelium and Pulmonary Macrophages. Am. Rev. Respir. Dis. 123:670-679 (1981). 10. Christman, J.W., Emerson, R.J., Graham, W.G.B., Davis, G.S.: Mineral Dust and Cell Recovery from the Bronchoalveolar Lavage of Healthy Vermont Granite Workers. Am. Rev. Respir. Dis. 132:393-399 (1985). 11. Craighead, J.E., Vallyathan, N.V.: Cryptic Pulmonary Lesions in Workers Occupationally Exposed to Dust Containing Silica. JAMA 244:1939-1941 (1980). 12. Jodoin, G., Gibbs, G.W., Macklem, P.T., McDonald, J.C., Becklake, M.R.: Early Effects ofAsbestos Exposure on Lung Function. Am. Rev. Respir. Dis. 104:525-535 (1971). 13. Jost, R.G., Sagel, S.S., Stanley, R.J., Levitt, R.G.: Computed Tomography of the Thorax. Radiology 126:125-136 (1978). 14. Kreel, L.: Computed Tomography ofthe Lung and Pleura. Semin. Roent genol. 13:213-225 (1978). 15. Lambert, R-, Bisson, G., Lamoureux, G., Begin, R.: Gallium-67 Thoracic Scan and Pleural Disease in Asbestos Workers. J. Nucl. Med. 26:600-603 (1985). 16. Rom,W.N., Bitterman, P.B., Rennard, S.I., Cantin, A., Crystal, R.G.: Characterization of the Lower Respiratory Tract Inflammation of Nonsmoking Individuals with Interstitial Lung Disease Associated with Chronic Inhalation of Inorganic Dusts. Am. Rev. Respir. Dis. 136:1429-1434(1987). 1197 Poster Session I EXPERIENCE WITH THE ILO CLASSIFICATION (1980) IN RELATION TO EXPOSURE TIME IN $ COAL MINES IN THE FRG W.T. ULMER (I. Bengtsson H.L. Reischig B. Speckmann * H.-J. Vautrin I. ZImmermann Pneumoconiosis Research Institute, Bochum (FRG) abstract 2347 coal miners were examined in 4 coal mines. The relation between exposure time and X-ray changes follow ing the ILO-classificadon 1980 is relatively linear. Therefore, for a single coal miner as for the mean value of a mine, an ``ILO-classification-step-time'' can be determined. Assessed according to ILO-classification categories, on die X-rays die increase shows the same augmentation after termination after 15 years of ex posure time as the group ofworkers still active. In the ILO-classification-step-time, there are tremendous dif ferences (1:10) between different coal workers as well as between mean values ofdifferent mines (1:7). From the ILO-classification-step-time, die useful time interval of X-ray reexaminations of coal workers can be detected, too. No Paper provided. Poster Session I LUNG FUNCTION MEASUREMENTS ON COAL MINERS W.T. ULMER 0. Bengtsson H.L. Reischig B. Speckmann H.-J. Vautrin Pneumoconisis Research Institute, Bochum (FRG) ABSTRACT We performed measurements of airway resistance, thoracic gas volume and arterial blood gases at die same time as X-ray examination with 2496 coal miners. The reagibility of airways was controlled by metacholinechallenge tests, too. There are age-dependents in 2 to 6,5% miners with signs of an obstructive airway disease. 9,5% showed a hyperreagibility of airways. The hyperreagibility was not age-dependent. There was no correlation between these lung function disturbances and X-ray changes. For the health situation of miners it is important to find out persons with obstructive airway disease in order to avoid a further deterioration of this affection. No Paper provided. 1199 Poster Session I VISCERAL PLEURAL THICKENING IN ASBESTOS EXPOSURE: THE OCCURRENCE AND IMPLICATIONS OF THICKENED INTERLOBAR FISSURES S. DAVID ROCKOFF,* M.D., F.A.C.R. Arnold Schwartz,* M.D. William Hix,*M.D. Prashant Rohatgl,* M.D. Elliot Kagan,t M.B., BCh, MRCPath David Kriebeht Sc.D. The George Washington University Medical Center (GWUMC), Washington, DC, USA tGeorgetown University Medical School, USA ^School of Public Health, Harvard Medical School, USA INTRODUCTION The interlobar fissures are lined by visceral pleura. We have noticed, radiographically, die frequent occurrence of thick ened interlobar fissures in asbestos exposed individuals, even when the lungs have been normal otherwise. Visceral pleural thickening in asbestos exposure has not received much atten tion in the diagnosis ofasbestos-related thoracic disease, hav ing been considered mainly to be an extension ofa more dif fuse pleural reaction to asbestos dust.1 However, indie 1980 revision of the I.L.O. classification, provision was made to indicate fissural thickening as being present or absent. We studied the significance of such thickening2 and describe the potential practical application of fissural thickening on radiographs as an early sign of asbestos exposure. The peripheral deposition of inhaled asbestos fibers in die lung3-5 and the fact that visceral pleural thickening is the usual find ing histologically in asbestosis,6 provides a reasonable ex pectation for a relationship between asbestos exposure and visceral pleural thickening radiographically. METHODS A control group of 100 adult male patients with no known asbestos exposure, with good quality posterior-anterior (PA) and lateral chest radiographs read as "no active disease" and admitted for non-thoracic problems were selected from 257 consecutive admissions, after 157 were excluded for inade quate radiographs and/or radiographic evidence of obvious cardiopulmonary disease. The radiographs were classified as to the presence and degree of fissural thickening. All had otherwise normal appearing lungs. The study group was comprised of 220 asbestos-exposed workers drawn from 241 consecutively encountered in dividuals participating in an occupational screening program, with 21 being eliminated for absence ofadequate radiographs or the presence of cardiopulmonary disease which could in terfere with the interpretation. The number ofyears since first occupational contact was recorded as a measure of asbestos exposure. The radiographs ofthe study group subjects were analyzed for die following factors:1 1. Parietalpleuralplaqueformation was noted to be pres 1200 ent, absent or questionable. 2. Interstitialpulmonaryfibrosis was noted as the presence or absence ofaccentuation ofthe nonvascular, fine linear hing markings ofthe type generally referred to as "small irregular opacities," without an attempt to grade die degree of profusion. 3. Fissural thickening was graded as 0 = Normal fissures, being <0.5 mm throughout; +/- = Questionable thickening, with areas of apparent thickening (>0.5 mm), which could represent either localized fissural thickening or superimposed fissures; 1 + = Minimal fissural thickening with definite, localized thickening of >0.5and <1.0 mm; 2 + = Moderate fissural thicken ing with definite, diffuse fissural thickening >0.5 and <1.0 mm, involving the equivalent of a large portion ofdie length ofa major or minor fissure, with or without localized plaques; 3 + = Marked fissural thickening was extensive, diffuse involvement of the fissure(s) as evidenced by thickening of virtually all of the major and/or minor fissures and/or thickening predominant ly >1.0 mm. In addition to the control and study groups, a series of in dividuals with clinically and/or histologically diagnosed asbestosis were studied to see whether asbestos-induced fissural thickening occurs in the absence ofpulmonary fibrosis and, regardless of the presence of radiographically-evident pulmonary fibrosis, to analyze die plain film and computed tomographic appearances ofvisceral pleural thickening in in terlobar fissures. STATISTICAL METHODS Group means were examined with Student's "t" test and the relationship between years since first exposure to asbestos and the occurrence of pleural abnormalities was investigated by fitting logistic models, as described in our earlier paper.2 These models corrected for die effect of the person's age on the data. RESULTS A. Control Group: Combining fissural thickening of0 and +/-degrees as "normal" and 14- to 3+ as abnormal, 84% had "normal" fissures while 16% had fissural thickening. Of those with fissural thickening, none was marked (i.e., 3+) with an equal distribution between "slight" and "moderate" thickening. B. Study Group: Definite fissural thickening was observed inS4.5% while 45.5% had radiographically "normal" fissures. The relationship between fissural thickening and years from first exposure is shown in Figure 1 where it is seen that the 50% probability of having fissural thickening occurs at 21 years after first ex posure. With regard to parietal pleural plaques, 38.2% had definite plaque formation while 61.8% had none. As shown in Figure 2, the 50% probability of having pleural plaques occurs 31 years after first exposure. Both the pleural plaques and die fissural thickening were associated with die length oftime since first exposure. These data show not only that fissural thickening oc curs some 10 years earlier than pleural plaque forma tion, but also that it is a more common lesion (i.e., 54.5% vs. 38.2%). However, the two types ofpleural changes generally occurred together with 85 % ofthose with parietal pleural plaques also having fissural thickening. Further, it was relatively uncommon to see radiographic evidence of pulmonary fibrosis in the absence of fissural thickening. C. Fissural Thickening in Clinical Asbestosis: In studying our series ofasbestosis patients, the radiographic find ing of fissural thickening was uniformly found even in die absence of diffuse chest wall pleural thickening. Pulmonary asbestosis was found histologically in the absence of radiographic changes in the lungs. (Figure 3) The uncalcified fissural thickening as seen on plain chest radiographs and on computed tomograms is demonstrated in Figure 4. In one of our cases, the fissure was calcified on CT only.7 DISCUSSION AND CONCLUSIONS The data presented suggest some interesting possibilities with regard to the earlier radiographic diagnosis of pulmonary asbestosis. While the relationship between radiographically visualized fissural thickening and underlying asbestos-induced pulmonary fibrosis has yet to be clarified definitively, the visceral pleura is part of the lung (unlike parietal pleural plaques) and thickening of it has been shown to be related to die concentration of asbestos fibers and bodies.8 A few comments are in order about radiographic techniques. The I.L.O. method9 uses only the frontal view, on which on ly the minor fissure of the right lung is routinely visualized. To achieve the results presented in our work, the lateral as well as the frontal view is required in order to visualize the major as well as die minor fissures. Based upon the observations we have marfo using frontal (PA) and lateral chest radiographs, we conclude the following:1 1. Fissural thickening is common in asbestos exposed in dividuals (54.5%) although it is not specific, being also Poster Session I seen in 16.0% of an unexposed control group. 2. Fissural thickening was found to be more common than pleural plaque formation in the asbestos-exposed popula tion (i.e., 54.5% vs. 38.2%). 3. An age adjusted analysis using logistic models showed that fissural thickening occurs, on an average, 10 years earlier after asbestos exposure than does pleural plaque formation (i.e., 21 years vs. 31 years). This means that fissural thickening can serve as an earlier, if not more specific, sign ofasbestos-related disease of the thorax. 4. The severity of the fissural thickening, when adjusted for age, increases with length of time since first exposed to asbestos, suggesting its direct relationship to the asbestos exposure. 5. The plain film and computed tomographic appearances ofthe fissural thickening ranges from isolated visceral pleural plaques to thickening involving entire fissures. Our cases rarely showed any relationship to diffuse, generalized pleural thickening. There are two potential practical clinical applications of the finding of fissural thickening on radiographs. First, if a per son is known to have been exposed to asbestos, it could be a marker ofearly involvement ofthe lungs as the result ofthe exposed and lead to appropriate inquiries. In individuals without known occupational exposure, the finding of unex plained fissural thickening could lead to inquiries which might indicate unusual spousal or environmental contact with asbestos dust, bearing in mind that isolated fissural thicken ing is a non-specific finding. REFERENCES 1. McLoud, T.C., Woods, B.O., Carrington, C.B., Epler, G.R., Gaensler, E.A.: Diffuse pleural thickening in an asbestos-exposed population: Prevalence and cause. Amer. J. Roentgenol. 144:9-18 (1985). 2. Rockoff,S.D., Kagan, E., Schwartz, A., Kriebd, D.,Hix,W.,Rohatgi, P.: Visceral pleural thickening in asbestos exposure: The occurrence and implications ofthickened interiobar fissures. J. Ihorac. bnag. 2(4):58-66 (1987). 3. Churg, A., Wright, J.L.: Small airways disease and mineral dust ex posure. Pathol. Ann. 18:233-252 (1983). 4. HiUerdal, G.: The pathogenesis of pleural plaques and pulmonary asbestosis: Possibilities and impossibilities. Ear. J. Respir. Dis. 61:129-138 (1980). 5. Deposition and clearance ofinhaledfibrous minerals in the rat. Studies using radioactive tracer techniques. Walton WH Ed., pp 259-274. In haled Particles IV Proc. Ini. Symp., Pergamon Press (1975). 6. Parkes, W.R.: Asbestos-related disorders. Br. J. Dis. Chest 67:261-300 (1973). 7. Rockoff, S.D.: CT Demonstration of Interlobar Fissure Calcification Due to Asbestos Exposure. J. Comput. Assist. Tomogr. 11 (6): 1066-1068 (1987). 8. Warnock, M.L., Kuwahara, TJ., Woleiy, G.: The relation ofasbestos burdento asbestosis and lung cancer. Pathol. Ann. 18:109-146(1983). 9. Guidelinesfor the Use cflLObuenuaional Classification ofRadiographs ofPneumoconioses. Occupational Safety and Health Series No. 22 (rev). Geneva, International Labour Office (1980). Note: Consult with author for figures. 1201 Poster Session I PREVALENCE OF CLINICAL AND RADIOGRAPHIC ABNORMALITIES IN 150 WORKERS EXPOSED TO NON-CALCINED DIATOMACEOCIS EARTH IN CENTRAL CALIFORNIA JOHN HOWARD,* M.D. B. Dwight Culver,* M.D. E. Nicholas Sargent,t M.D. Southern Occupational Health Center, University of California, Irvine, CA, USA tDepartroent of Radiology, University of Southern California, Los Angeles, CA, USA INTRODUCTION Diatomaceous earth, or diatomite, is a siliceous sedimentary rock composed essentially of the skeletal remains of microscopic single-celled aquatic plants called diatoms. Diatomite is a valuable material with a range ofindustrial uses. World production is approximately 1.6 million short tons, 45 % ofwhich is from the United States. California accounts for more than half of United States production.1 Diatomite consists primarily ofan amorphous silica contain ing a small percentage ofcrystalline silica detectable by con ventional X-ray diffraction analysis. In the past, diatomite pro cessing included calcination which involves beating die natural diatomite to high temperatures, with or without an alkaline flux, thereby converting the amorphous silica into a fibrogenic crystalline form called cristobalite. The cristobalite content of natural (unealcined) diatomite in typically less than 1%; that of straight-calcined 10-20%; and that of flux-calcined products 40-60%. Pneumoconiosis in the diatomite industry has been associated with exposure to calcined products containing cristobalite. In 1953, a United States Public Health Service survey in Califor nia demonstrated a 25% prevalence rate ofpneumoconiosis among diatomite workers who had been employed for five years or more.2 Since that time, dust control measures have been instituted throughout the diatomite industry and calcination ofthe natural diatomite has largely been eliminated. Subsequent surveys of the diatomite industry have demonstrated the effectiveness of dust control measures.3 In 1983, a medical surveillance program was begun at Excel Mineral Company, which processes sedimentary rock (characterized as diatomaceous earth) into cat litter absorbent. This report summarizes data on the respiratory symptoms, pulmonary function studies and chest roentgenograms of 150 employees with at least five years ofcontinuous employment at Excel Mineral Company. SUBJECTS AND METHODS Study Population Excel Mineral Company is located in the southern San Joa quin Valley ofCalifornia and operates two plants at Taft and McKittrick. All current employees at both plants participated 1202 intwo medical surveillance surveys done by the Southern Oc cupational Health Center ofthe University ofCalifornia at Ir vine. Only employees with at least five years of continuous employment at Excel were included in this report. Exposure Index Since only scant personal monitoring dataexisted on the level of past dust exposure, an exposure index (E.I.) was con structed. First, employee tasks were subdivided into eight categories: (1) mining; (2) milling; (3) packaging; (4) loading dock; (5) delivery; (6) administration; (7) maintenance (in side plant); (8) maintenance (outside plant). Next, these eight job categories were divided into "dusty" 1,2,3,7 and "nondusty"4,5,6,8jobs based on the results ofa 1977 personal hygiene study. A dustyjob was one in which dust concentra tions exceeded 10 mg/cc3. A year spent at a dusty job prior to 1971 (when dust controls were nonexistent) was counted as the equivalent of two dust-years of exposure after 1971. A year spent in a non-dustyjob either before or after 1971 did not contribute to the exposure index. Therefore, die E.I. represents the sum of twice a pre-1971 dust-year plus a post-1971 dust-year. Study Protocol All current employees participated in medical surveillance surveys done in 1983 and 1988 which included a selfadministered health history questionnaire, pulmonary func tion studies and chest roentgenograms. The questionnaire elicited information about general medical conditions, specific respiratory system complaints and a com plete occupational history. The presence of any one of the following respiratory complaints ofcough, wheezing, chest tightness and dyspnea was included in calculation of a total respiratory symptom score. The symptom score ranged from zero (no symptoms present) to four (all four symptoms present). Spirometric pulmonary function studies were done on site and consisted of a forced vital capacity (FVC) and forced ex piratory volume in one second (FEVj). Spirometry was per formed by a NIOSH-trained technologist on an 8-L Collins portable recording spirometer (Warren E. Collins, Braintree, MA) which met NIOSH apparatus criteria. Predicted values were based on Knudson's regression equations.4 A single posteroanterior chest roentgenogram was obtained at a nearby physician's office and was interpreted blindly by one ofthe authors (ENS) according to the ILO Classification of the Pneumoconioses (1980).5 Mineral Analysis Ore from the opencast mine was sent to Clayton Environmen tal Consultants, Inc. (Southfield, Michigan) for complete mineral content analysis. In addition, dust from several areas in both plants was sent for microscopic particle sizing and mineral analysis including a determination ofdie proportional content of amorphous and crystalline silica (alpha-quartz, cristobalite and tridymite). Statistical Analysis Comparisons between exposure groups were done with Stu dent's two-tailed, chi-square test with and without Yates' con tinuity correction, and Fisher's exact test. RESULTS One hundred fifty (121 males and 29 females) employees pres ent for the 1983 survey who were continuously employed at Excel and present for the 1988 survey were included in this analysis. All subjects were subdivided into three approximate ly equal categories based on exposure index. Group I (n=82) had an E.I. of zero to eight years. Group n (n=47) had an E.I. of nine to sixteen years, and Group IQ (n=21) had an E.I. of seventeen or more years. All three groups were com parable (P >.13) in sex, age, race, and tobacco smoking history. Respiratory Symptoms Respiratory symptom scores increased with exposure index. Group I had a symptom score of0.8, Group n 1.0 and Group TTI 1.4. (P=.048) In all three Groups, a large proportion of employees complained of wheezing (Group 126%, Group II 23% and Group HI 43%). Pulmonary Function Tests Spirometry revealed no obstructive or restrictive defects. Group I had an FVC of 90.6%, and FEV! of 78.9% of predicted. Group n had an FVC of 88.0%, and FEVi of 79.8% of predicted. Group HI had an FVC of 87.9%, and FEV i of 79.1 % of predicted. There was no significant dif ference in pulmonary function among the three groups. Roentgenographic Findings Eleven employees (7%) had chest roentgenograms which demonstrated parenchymal abnormalities of doubtful significance for pneumoconiosis (profusion score of 0/1 or 1/0). Three employees (2%) had parenchymal abnormalities on chest roentgenograms consistent with pneumoconiosis (profusion score of 1/1 or greater). Of the three employees with films consistent with pneumoconiosis, one employee's film in Group II had a pro fusion score of2/1 and two employees' films in Group in had scores of 2/1 and 2/2. Of note, the three employees whose films demonstrated pneumoconiosis were employed for a total of9,20,21 years, respectively. There were no parenchymal Poster Session I abnormalites suggestive ofirregular or large opacities. In ad dition, no pleural findings were seen. Mineral Analysis Microscopic sizing of dust samples taken from the mill area at both plants revealed a respirable dust content (two microns or less) of 91 % of particles. Mineral analysis by X-ray dif fraction of both ore and dust samples revealed a mean pro portional silica content of 75 %, chiefly in the form of amor phous silica (mean 69%) and crystalline silica (mean 6%). Crystalline silica was present in two forms: alpha-quartz (mean 2%) and cristobalite (mean 4%). The mineral content of ore and area dust samples did not differ appreciably. DISCUSSION In the past, the prevalence rate of pneumoconiosis in the diatomite industry in California was 25 %. Recent surveys of employees in the California diatomite industry have demonstrated a steadily decreasing pneumoconiosis prevalence rate. In fact, a survey in 1984 revealed that only 6 employees out of473 (2.3%) had films which were classified 1/2 or higher and these employees had been employed in diatomite processing for more than 25 years.3 In our survey, we expected to find an even lower pneumoconiosis prevalence rate than previously published surveys for several reasons. First, calcining at Excel antedated the employment of nearly all members of the current workforce. Second, control measures at Excel have reflected the industry standard for a number of years. Third, we ex pected that mineral analysis of the natural, uncalcined diatomite would yield a crystalline silica content lower than the 6% mean figure obtained. In our survey, we found a pneumoconiosis prevalence rate (2%), which was slightly less than previous surveys. Of con cern, however, is the fact that employees with positive films had worked in the diatomite industry for much shorter periods of time than those employees with positive films described in other studies. Mineral analysis of the ore and dust may provide some ex planation for the pneumoconiosis prevalence rate found. Since the content of fibrogenic crystalline silica seen in the Excel ore and dust exceeds what is generally found in uncalcined diatomite, employees at Excel may be at greater risk than other employees in the diatomite industry. Further study of this population is planned. REFERENCES 1. Villota, R., Hawkes, J.G.: Food Applications and the Toxicologica] and Nutritional Implications of Amorphous Silicon Dioxide. CRC Crit. Rev. in FoodServ. andNutrit. 23:289-321 (1987). 2. Cooper, W.C., Craiiey, L.S.: PneumoconiosisinDiaiomiteMiningand Processing. Public Health Service Publication 601. Washington, D.C. (1958). 3. Cooper, W.C., Sargent, E.N.: A 26-Year Radiographic Follow-Up of Workers in A Diatomite Mine and Mill. J. Occ. Med. 26:456-460 (1984). 4. Knudson, R.J., Slatin, R.S., Lebowitz, M.D., Burrows, B.: The Max imal Expiratory Flow-Volume Curve: Normal Standards, Variability and Effects of Age. Am. Rev. Respir. Dis. 113:567 (1976). 5. Guidelines for the Use of ILO International Classification of the Radiographs ofPneumoconioses. International Labor Office. Geneva (1980). 1203 Poster Session / PROGRAM TO PREVENT ASBESTOS-INDUCED HEALTH HAZARDS IN FINLAND--ASBESTOS PROGRAM IN FINLAND M.S. Huuskonen H. Koskinen H. Valnio A. Tossavainen J. Rantanen Institute of Occupational Health, SF-00250 Helsinki, Finland The Institute ofOccupational Health (IOH) started a program to prevent asbestos-induced hazards in 1987. Special emphasis is placed on primary and secondary prevention of asbestosrelated cancers. The program involves die dissemination of information, training, services, and research. The IOH is car rying out the program together with the authorities, industry, unions, the health care system, and insurance companies. The program aims to prevent asbestos-related health hazards (by minimi?ing exposure to asbestos and by educating workers already exposed), to assess the risks caused by exposure to asbestos, and to improve die diagnosis of asbestos-related diseases in Finland. EXPOSURE TO ASBESTOS IN FINLAND The use of asbestos in new production was highest between 1965-1975 (about 12,000 tons annually). Some asbestos prod ucts are still produced, but the authorities have stipulated that the manufacture ofall asbestos products should cease by 1995. This stipulation, however, does not mean that exposure to asbestos will cease, because asbestos is present in nearly all buildings, ships, etc. built beforel975-1980. More and more old buildings are being renovated. Potential asbestos sources have been assessed only in a few cases. Because of this in sufficiently controlled, and on-going, situation, both direct and indirect exposure to asbestos has been more common than is generally realized. Besides occupational environments there are many non-occupational sources of asbestos exposure: refitting schools, hospitals, garrisons, and other public buildings. The goal is to stop using asbestos in new produc tion and to assess die potential asbestos exposure before plan ning work to renovate old buildings. When asbestos is pres ent, work should always be done so that neither workers nor the environment is exposed. According to a rough estimate, there are more tnan 200,000 currently active or retired workers in Finland who have been exposed to over 2 fb/ml for a period of at least two months. Altogether some 50,000 workers (mainly from the construc tion industry) over 40 years ofage have been working in the construction branch for more than 10 years. Thus, on the basis ofwhat is known about the exposure situation in Finland, in cidence of asbestos-related diseases will reach its peak dur ing the first decade of the next century. ASBESTOSIS A total ofabout 550asbestosis cases were diagnosed between 1938-1987. In die last few years, 30-40 cases of asbestosis have been diagnosed annually. Preliminary data from the screening of about 1,000 construction workers suggest that 1204 there are many more undiagnosed asbestosis cases. The mean age ofthe surveyed groups was 59 years, and die workers had been employed in the construction branch in 1967. One in four screened construction workers had positive parenchymal and/ or pleural findings; almost all ofdiem were ignorant of their clinical status. When interviewed, they reported an average of3.7 years ofasbestos exposure. Halfofthem were retired. The routine health care system had been unable to trace the subjects for further clinical evaluation. It can be inferred that the number of undiagnosed cases of asbestosis is thus equal to or even higher than the number of diagnosed cases. ASBESTOS AND CANCER A large proportion ofthose who develop asbestosis will even tually die of cancer. Of the previously diagnosed Finnish asbestosis patients, about 40% have died of lung cancer, 5-10% of mesothelioma, and 10% of other cancers. At the IOH 130 asbestosis patients have been followed from 1980 to 1985. Eighteen ofthese 130 patients have contracted lung cancer within this observation period. The rough annual lung cancer incidence is thus 2.3/100. About 2,000 incident lung cancers are found annually in Finland. Smoking is the most important etiological factor. The etiologic fraction ofoccupational exposures in the rise ofhing cancer varies between 13% and 35%. Asbestos is the most important single occupational cause oflung cancer.5,6 In one study it was estimated that 23% of lung cancers could have been prevented by eliminating asbestos exposure.6 About 50 pleural mesothelioma cases are diagnosed in Finland each year. The number has tripled in foe last 10-15 years. More than 80% of foe diagnosed mesothelioma cases have been exposed to asbestos.12 Only a few peritoneal mesotheliomas have been diagnosed in Finland. TIME FACTORS IN ASBESTOS-INDUCED CANCER The studies on asbestos insulation workers suggest that the risk of lung cancer may decline as foe length offoe observa tion period increases. In a cohort of 17,800 asbestos insula tion workers, Selikoff A al11 found that foe relative risk of lung cancer begins to increase ten years from foe first such employment, rises to a maximum at 30 to 40 years from foe first employment, and then falls. A symmetrical bell-shaped curve with a peak at 35 years from foe first employment is a good representation of this relationship.8 Asbestos and smoking increases foe risk of lung cancer multiplicatively; asbestos increases foe relative risk of lung cancer similarly among both smokers and nonsmokers.2,3'4 Peto et al9 have shown that, among asbestos-exposed work ing, die mesothelioma death rates are proportional to the third and fourth power of time from the first exposure. This rela tionship occurs in a wide range ofconditions ofexposure and is independent of the worker's age when initially exposed. These findings suggest that asbestos induces mesothelioma by acting in the early stages ofcarcinogenesis, while asbestos in duces lung cancer by acting in the late stages of car cinogenesis. This means that slight exposure at early age could have an important effect in inducing mesothelioma but a negligible effect in inducing lung cancer. In contrast, a high exposure level when middle-aged has an important effect in inducing lung cancer after a relatively short period which is approximately linearly proportional to die dose. Time considerations may have an important bearing on calculations to determine the amount of asbestos-related malignant disease that can be expected to occur in the future. It may also be important with respect to chemoprevention, especially chemoprevention of lung cancer caused by asbestos. CANCER CHEMOPREVENTION AMONG ASBESTOS-EXPOSED WORKERS Vitamin A and beta-carotene (provitamin A) have attracted attention as possible cancer prevention agents.1*13 In retrospective epidemiological studies, subjects with low serum concentrations or low estimated dietary intakes ofcarotenoids, beta-carotene, or retinol have had an increased incidence of developing cancers as compared with matched cohorts hav ing high to normal serum concentrations of these micronutrients. Vitamin E is able to act as a radical trap in lipid membranes. Some experimental studies have suggested that vitamin E has an inhibitory effect on the development of tumors in ex perimental animals induced by chemical carcinogens. Rele vant epidemiological studies are limited, hi two cohort studies, no relationship was found between vitamin E levels and risk of cancer at all sites combined13 or for various sites.10 However, in two other cohorts, significandy lower vitamin E levels were observed among women14 and men7 who subsequendy developed cancer than among their controls. A prospective intervention trial involving administration of beta-carotene and vitamin E to asbestosis patients and subjects heavily exposed to asbestos is presently being planned. The aim is to determine whether daily treatment with beta-carotene (20 mg) and/or vitamin E (SO mg) could result in a lower in cidence of(lung) cancer in groups receiving the active treat ment as compared to the incidence in the group receiving a placebo. DIAGNOSTICS AND COMPENSATION Asbestos-related diseases, including malignancies, have been known for decades. According to die Finnish occupational health legislation, all those with asbestos-induced diseases are eligible for compensation. The information on occupational exposures should therefore be gathered for every mesothelioma and lung cancer patient, hi every case die causal importance ofasbestos should be evaluated from die medical point of view. Poster Session I SUMMARY There is no known safe level of exposure to asbestos at work. Primary prevention is the main goal of die asbestos program ofthe IOH. Primary prevention carried out today can reduce the disease incidence in future decades. The present disease panorama is die consequence of past exposures (mainly before the 1970s). The peak in asbestos-induced diseases will be reached 15-20 years from now. The annual number of asbestos-related premature deaths is estimated at present to be about 150, which exceeds the annual number of fatal oc cupational accidents. The number of pleural mesotheliomas has tripled in the last 10-15 years, and is now about 50/year. Only in a few cases of mesothelioma has there been no rele vant asbestos exposure. However, clinicians have paid very litde attention to exposure to asbestos. Therefore most cases are not registered as occupational diseases, and no claims are filed with insurance companies. Informing and training hospital medical staff is essential to improve the situation. The termination of exposure, antismoking campaigns, improved diagnostics, and careful attention to compensation issues, as well as clarifying the potential for chemoprevention, are the central points of the asbestos program of the IOH. REFERENCES 1. Committee on Diet, Nutrition and Cancer. Assembly ofLife Sciences, National Research Council: Diet, Nutrition and Cancer. National Academy Press, Washington, D.C. (1982). 2. Blot, W.J., Harrington, J.M., Toledo, A., et al.: Lung cancer after employment in shipyards during World War n. N. Engl. J. Med. 299:620-624 (1978). 3. Blot, WJ., Morris, L.E., Stroube, R., etal.: Lung and laryngeal cancers in relation to shipyard employment in coastal Virginia. J.N.C.l. 65: 571-575 (1980). 4. Hammond, E.C., Selikoff, I.J., Seidman, H.: Asbestos exposure, cigarette smoking and death rates. Ann. N. . Acad. Set. 330: 473-490 (1979). 5. Kjuus, H., Skjaerven, R., Langard, S., et al: A case-referent study of lung cancer, occupational exposures and smoking, n. Role ofasbestos exposures. Scand. J. Work Environ. Health 12:203-209 (1986). 6. Kjuus, H., Langard, S., Skjaerven, R.: A case-referent study of lung cancer, occupational exposures and smoking. DI. Edologic fractions of occupational exposures. Scand. J. Work Environ. Health 12:210-215 (1986). 7. Knekt, P., Aromaa, A., Maatela, J., et al.: Serum vitamin E and risk ofcancer among Finnish men during the 10 year follow-up. Am. J. Epid. 127(1988) 28-41. 8. Nicholson, W.J., Perkel, G., Selikoff I.J.: Occupational exposure to asbestos: Population at risk and projected mortality, 1980-2030. Am. J. Ind. Med. 3:259-311 (1982). 9. Peto,J.,Seidman,H.,Selikoff,I.J.:Mesotheliomamortalityinasbestos workers: Implications for models ofcarcinogenesis and risk assessment. Br. J. Cancer 45:124-135 (1982). 10. Salonen, J.T., Salonen, R., Lappetelainen R., Maenpaa, P.H., Alftan, G., Puska, P.: Ride of cancer in relation to serum concentration of selenium and vitamins A and E: matched case-control analysis of pro spective data. Br. Med. J. 290 (1985) 417-420. 11. Selikoff, I.J., Hammond, E.C., Seidman, H.: Mortality experience of insulation workers in the United States and Canada 1943-1976. Ann. N. Y. Acad. Sci. 330:91-116 (1979). 12. Tossavainen, A., Huuskonen, M.S., Tuomi, T., et al.: Asbestos ex posure among Finnish Mesotheliomapatients. Presented at VTIth Inter national Pneumoconioses Conference. Pittsburgh, August 23-26 (1988). 13. Willett, W.C., Polle, B.F., Underwood, B.A., et al.: Relation ofserum vitamins A and E and carotenoids to risk of cancer. N. Engl. J. Med. 310:430-434 (1984). 14. Wald, N.J., Boreham, J., Hayward, J.L., Bulbrook, R.D.: Plasma retinol, carotene and vitamin E levels in relation to the future risk ofbreast cancer. Br. J. Cancer 49:321-324 (1984). 1205 Poster Session / STUDY ON HAEMOLYTIC ACTIVITIES OF 10 TYPES OF COAL MINE DUSTS AND THEIR EFFECT FACTORS XING GUO-CHANG LuiTie-Min LuiZung-Qi Zhou Chen Institute for Occupational Medicine of Ministry of Coal Industry, Beijing, China INTRODUCTION Prevalence rate ofC.W.P. differs not only in different coun tries, but also in different coal mines in one country.1,2,3 It is so in China. Of course, die difference is due to many fac tors. Walton, et al4 and Reisner, et als suggested that an unknown factor or factors must play a major role in determin ing die pneumoconiotic potential of individual dusts. The haemolytic test is a simple and reliable method for estimating cytotoxicity ofsilica mineral dusts, which was one of the first systems used for exploring mineral dust cytotoxicity6 and later on for cytotoxicity of colliery dust.7 Reisner, et al5 found that cytotoxicity or coal dust was cor related with the pneumoconiosis risk obtained by epidemiological survey. In the present study, a vitro haemolytic technique was used to estimate preliminary cytotoxicity ofmost colliery dusts in China, providing scientific basis for fibrogenic potential of different colliery dusts. MATERIALS AND METHODS Preparation of Erythrocyte Suspensions Healthy male New Zealand rabbits weighing 3 Kg were used for this study (provided by Animals Centre of Academy of Medical Sciences ofChina). Blood was drawn from the heart, centrifuged at 2000 rpm for 20 min., diluted with sterile physiological saline to make a 2% erythrocyte suspension. Preparation of Dust Suspensions 10 types ofcoals used in this study were Fat Coal, Anthracite, Cindery Coal, Meagre Coal, Candle Coal, Weak Caking* Coal, Gas Coal, Lignite, Non-Caking Coal and Lean Coal, provided by Academy ofCoal Science ofChina. The elemen tal compositions were listed in Table I and Table n. These coal samples were crushed in agate mortar to die particle size distribution less than 3 inn in dia. accounting for over 95%. Standard quartz dust less than 5 pm in dia. accounts for over 99 %, provided by Academy of Preventive Medical Science of China. A series ofdust samples were dried, sterilized tty ultraviolet ray for 30 min., suspended in sterile physiological saline to make the certain concentration and shaken in a high-speed water bath shaker for complete suspension. 1206 Experiment Groups Coal groups: 10 types ofcoals were divided into 10 groups. 3 ml erythrocyte suspensions were added into 2 ml of20 mg/ml to 10 types of coal dust suspensions respectively and then incubated in IDI Water Bath Oscillator (at 37 0.S temperature, 120 times per min, cyclo-oscillation) for 60 min. The suspensions were centrifuged at2000 rpm for 60 min and the optical density of the suspensions was measured at 540 nm in a 721 Spectrophotometer. Quartz control groups: Quartz control I: 0.16 mg/ml. Quartz control II: 1.25 mg/ml. Different Concentrations of Coal Groups A series of Anthracite, Candle Coal and Non-Caking Coal were used as different doses ofcoal-groups (5,10,20 and 40 mg/ml). Completely Lysed Control and Erythrocyte Fragility Control 3 ml of 2 % erythrocyte suspension was centrifuged at 2000 rpm for 20 min and added with 5 ml distilled water to make a complete lysis control. 2 ml of2% erythrocyte suspension was mixed with 2 ml physiological saline to make an erythrocyte fragility control. % of haemolysis = ODS40 Test Sample - OD540 Fragility Control x ^ OD340 Fully Lysed Control RESULTS Comparison of Haemolytic Activities among 10 Types of Coal Dusts Results of tests done repeatedly 17-20 times are shown in Figure 1 and Table m. It is clearly seen that haemolytic ac tivities of 10 types of coal dusts were different. Degree of haemolysis by Lean Coal and Fat Coal was respectively lowest and highest (range 10-35 %). Statistics showed that haemolytic activities ofquartz control I and II were significantly higher than those of coal dust-groups and that haemolytic activities of different doses of coal dust-groups were significantly Table I Composition of 10 Types of Coals Types of Ash Volatility Coal (g * ) Anthracite 22.962 77571 > of ja Of Carbon Hvdroeen 79.944 l.obo ia Of Nitrogen 0.715 Lean Coal lb.390 16.067 73.293 3.776 1.111 Cindery Coal 2*4.79b lb.623 b4.671 3.74b 1.012 Gas Coal 11.244 29.332 76.436 4 .640 1.323 Candle Coal 11-369 35-763 70.424 4.593 0.723 Lignite 10.042 41.623 63.925 4.020 O.96O Weak Caking Coal 10.3^0 26.150 71.680 4.380 Non-Caking 5.940 Coal Fat Coal 35-780 26.550 22.290 63.430 57.380 3.430 3.700. 1.040 Meagre Coal 23.640 14.800 67.200 4.300 1.560 Poster Session I Types of CoaJ s Anthracite Lean Coal ft of Sio^ 52.67 or 5.31 46.59 13.83 C.imiery Coal Gas Coal 46.47 59.42 11.33 5.42 Cartd 1 e Coal 4 9,08 7.94 Lignite 50.42 12.25 Weak Caking Coal 52.16 21.47 Fat Coal 48.67 4.90 Meagre Coal 49.77 3.34 Table n Composition of Ashes of 10 Types of Coals > of At2'i 30.89 30.08 > of Cao 4.13 3.40 > of MgO 0.99 0.67 '0 of SU3 1.08 1.96 % of Ti02 1.13 1.57 25.05 26.75 7.07 2.367 1.59 O.67 4.59 1.61 1.12 1.16 32.81 22.18 3.49 6.68 1.26 1.16 1.23 3.58 1.44 1.06 17.15 35.04 2.38 3.78 35.71 3.95 1.09 1.92 1.54 2.54 2.90 O.54 1.92 1.48 1.31 it of K20 1.46 O.76 0.89 1.26 1.13 1.52 1.06 % of Na20 0.80 0.45 i vf P?5 0.47 o.n 0.75 0.33 0.09 0.08 0.42 0.552 0.34 0.18 0.12 1207 Poster Session I Mean P e rc e n t o f H a e m o lysis 1208 Figure 1. Mean percent of haemolysis of 10 types of coals--(1) Fat Coal, (2) Anthracite, (3) Cindery Coal, (4) Meagre Coal, (5) Candle Coal, (6) Weak Caking Coal, (7) Gas Coal, n.(8) Lignite, (9) Non-Caking Coal, (10) Lean Coal, (11) Quartz I, (12) Quartz Table HI Endangerment Levels of Coal Dusts Types of Coals Haemolysis Fat Coal Anthracite Cindery Coal 33-26 Meagre Coal Candle Coal Weak Caking--Coal Gas Coal 21-16 Lignite Non-Caking Coal Lean Coal 13-10 Levels Highest High Low different (P <0.01, analysis of Variance). Further F-Test showed that except for Anthracite and Candle Coal, Lignite and Lean Coal, haemolytic activities of remaining coal dusts showed statistical significance. Therefore, 10 types of coal dusts were divided into three levels by haemolytic activities, listed in Table HI. Comparison of Haemolytic Activities by the Different Doses of Coal Dusts Anthracite, Candle Coal and Non-Caking Coal were selected as representatives ofthree levels ofcoals as defined above for dose-response test. The results are shown in Figure 2. Haemolytic activities of Anthracite, Candle Coal and Non Caking Coals were respectively highest, high and low. But at die dust dose less than 10 mg/ml, their haemolytic activities were not significantly different. Starting from die dose of 10 mg/ml, their haemolytic activities increased with increasing dust doses. Analysis of Effect Factors on Cytotoxicities of Coal Dust Experimental data were analysed by multiple regression technique using computer to investigate die relationship among % Carbon content (Xi), % Ash content (X2), % SiO^ content (X3) and % AIO3 content (X4) in dusts and Poster Session I haemolytic activities of dusts (Y). The analysis results were as follows. Relationship between Y and Xj, r = 0.89 Relationship between Y and X2, r = 0.98 Relationship between Y and X3, r = 0.92 Relationship between Y and X4, r = 0.94 Where r is Correlation coefficient. Maximum amount comtributing variance were put into the equation. The result was: Y = -2.382418 + 1.651106X2 + 2373641X3 Statistics showed that % of Ash content and SiC>2 in dusts made the largest contribution to variance. DISCUSSION Many scholars suggested a lot ofhypothesis to explain the dif ference of C.W.P incidence rate in different coal mines with same dust concentration and similar workers' exposure time to dust. Some5 thought that it was related to geological age and coal rank. Some2 have identified rank and volatility of coal as factors associated with pneumoconiosis. Others10 thought that it was related to non-coal mineral component and Figure 2. Relation between concentration and percent of haemolysis. 1209 Poster Session I Types of* Coals Fat Coal Table IV Statistical Analysis of Mean Percent of 10 Types of Coals Number of* Replicates 20 % of Haemolysis Mean Standard Error 33.04 3-95 Anthracite 17 32.30 12.41 Cindery Coal 18 26.17 3.23 Meagre Coal 19 21.10 2.22 Candle Coal 18 19.43 2.43 Weak Caking Coal Gas Coal Lignite 20 17 19 18.48 16.39 13.1^ 6.92 3.04 4.21 Non-Caking Coal Lean Coal 19 18 11.60 10.63___ 4.46 2.74 15.60 154.01 10.43 4.93 5.91 47.89 9.24 17.72 19.89 2.51, ash content. Others7 thought rank and chemical composition ofcoal were important. A must be pointed (Hit that unanimity of opinion has not been reached on die role played tty Si02 in the development of pneumoconiosis. Some scholars11,12 think that quartz, even if a small amount ofit exists in dust, plays a role in developing pneumoconiosis, but others13 don't agree with this opinion. Our experiment showed that from large to small sequence ofhaemolytic activities ofcoal dusts were Fat Coal, Anthracite, Cindery Coal, Meagre Coal, Can* die Coal, Weak Caking Coal, Gas Coal, Lignite, Non-Caking Coal, and Lean Coal. The mean haemolytic activities of 10 types of coals were listed in Table IV. It was clearly seen that haemolytic activity ofcoal was associated with coal type which is related to the geological age. Although times and conditions of coal formation and country rock component have an effect on coal quality, i.e. ash content and component, coal rank and carbon and ash con tent in 10 types ofcoals are in above order ofhaemolytic ac tivity but volatility increased. Therefore, we think that SiC>2 in coal dusts plays an important role in cytotoxicity, which effect of coals themselves is related to period ofcoal forma tion. But other factors such as coal rank, volatility carbon con tent, ash content and SiC>2 content etc. are related to period or coal formation and are affected by condition of coal for mation and country rock component. REFERENCES 1. National Coal Board: Medical Service and Medical Research Annual Report 1979-1980. Lorion (1982). 2. Costantino, J.P.: BCR Pamphlet No. 2. Facts about Coal Worter's Pneumoconiosis. Bituminous Coal Research, INC, Pittsburgh (1982). 3. Morgan, WJLC.: OccupationalLungDiseases,2od&L,pp. 397, WJ. Saunders Co., Philadelphia (1975). 4. InhaledPanicles, IV. pp. 669-690. W.H. Wallin, Ed- Fergamoo, Ox ford (1977). 5. tV International Pneumoconiosis Conference. Relation between Pneumoconiosis and Dust Exposure in West-German Coal Mine, Geneva, ILO (1984). 6. bi Vitro Effect ofMineral Dusts, p.2. E.G. Beck and J. Bignon, Eds. NATO ASL Services, Springer-Verlay, Berlin (1985). 7. Davis, J.M.C. et al: Studies on the Cytotoxicity ofCoal Dust Samples, Including the Effect ofAbsorbed Nitres Fumes. Pathology Branch, In stitute of Occupational Medicine, Final Report on CEC Countreat 6244-00/8/105. Edinburgh ( ). 8. Morgan, W.K.C. et al: The Prevalence of Coal Worker's Pneumoconiosis in U.S. Coal Mines. Arch. Environ. Heath 27:221-226 (1973). 9. Hurley, J.F. et al: Coal Worker's Simple Pneumoconiosis and Exposure to Dust at 10 British Coal Mines. Brit. bid. Med. J. 39:120-127 (1982). 10. Reisner, M.: Pneumoconiosis and Dust Exposure Epidemiological Studies in the Ruhr Coal Miner During A Period of 14 Tears. Silikosebericfat Nordrhein-West Falen. 10:209-231 (1973). 11. Spencer, H.: Pathology ofthe Lung, 4th Ed. pp. 443-445, Perganxm Press, Oxford (1985). 12. WHO: Recommended Health-BasedLimits in Occupational Exposure to SelectedMineral Dusts (Silica, Coal). WHO Technical Report Scries 734. Geneva (1986). 1210 Poster Session I HIGH-SPEED, HIGH-RESOLUTION X-RAY COMPUTED TOMOGRAPHS IN THE DIAGNOSIS OF PNEUMOCONIOSIS HISAO SHIDA,* M.D. Keizo Chiyotani,f M.D. Yutaka Hosoda,^ M.D. *Div. of Radiology, Rosai Hospital for Silicosis, Japan |Div. of Internal Medicine, Rosai Hospital for Silicosis ^Radiation Effect Foundation INTRODUCTION Improvement in CT scanner technology now allows imag ing ofthe lung with excellent anatomic detail demonstrating both normal and abnormal intersdtium, patterns ofpulmonary abnormalities caused by dust inhalation and morphologic characteristics of localized or generalized parenchymal pro cesses, by circumventing the summation of lung structures in complex anatomic regions such as apices, paratracheal, perihilar, pericardiac, lateral margin of chest walls and diagphragmatic regions. The Fourth generation CT (TOSHIBA TCT 900S) can confirm the presence of pneumoconiotic nodular or interstitial fibrosis associated with areas of lung destruction and disorganization of lung architec tures results in a cystic appearance to the lung, bulla, bleb, pulmonary emphysema, broncho-bronchiolectasis, pneumothorax, pleural thickening or plaque and effusion, even if conventional plain chest radiographs cannot visualize these abnormalities. METHOD A comparative study between CT and P-A view ofcomputed radiography or conventional chest radiography was made of 108 cases of pneumoconiosis including silicosis, asbestosis, welder's lung, foundry worker's lung and activated carbon pneumoconiosis, the profusion of which ranged from 0/1 to 3/3 according to the ILO 1980 International Classification of Pneumoconiosis. Special filter function of FC3 and FC4 were provided to visualize detailed images of pulmonary parenchymal or in terstitial abnormalities. RESULTS The high-speed, high-resolution CT has a high detectability for the abnormalities of pulmonary parenchyma or interstitium and pleura. The presence of emphysematous changes including bulla, bleb, honeycombing, pleural thickening or plaque, septal thickening, subpleural strand, broncho-bronchiolectasis and very small rounded or very fine irregular opacities, can be confirmed, as shown in Table I. It is considered drat the CT will greatly increase die sensitivity of imaging techniques in detecting pneumoconioses and it is a useful procedure in the diagnosis of pulmonary disease at present. DISCUSSION In some cases of pneumoconiosis, very small rounded opacities can be difficult to distinguish from vessels seen in the thin cross-section. As general use it is recommended to take image with 5.0 to 10.0 mm in slice thickness. 1211 Poster Session I Table I Detectability of CR and CT in 108 Cases of Pneumoconiosis bulla bleb 10 FT 3 (3%) h 2 (2%) chest radiograph computed tomographs 20 30 40 50% _l 24 (22%) 28 (26%) pula, eaphyseaa boneycoabing pneuaotborax 0 13 (12%) 1 5 (5%) 9 (8%) h 2 (2%) pleural thickening and plaque coalescense of nodules 16 (15%) egg. shell calcification 1 7 (6%) 14 (14%) 1212 Poster Session / Figure 1. Case 1. 55 year-old, male, silicosis 1/1, P. CT images demonstrate dense dissemination offine silicotic nodular high densities throughout lungs. It is noteworthy that these nodules are more clearly and densely distributed than the conventional chest radiograph. 1213 Poster Session I Figure 2. Case 2. 60 year-old, male, silicosis 2/2, q. CT images reveal dense dissemination ofsilicotic nodular high densities throughout lungs ofwhich diameter is larger than thatofthe case 1. Subpleura] blebs andbullae are characterized on the CT images, (arrow) 1214 Poster Session I Figure 3. Case 3. 67 year-old, male, silicosis 2/2, q, es, px. A chest computed radiograph shows dissemination of silicotic nodular high den sities throughout lungs and minimal pneumothorax ofdie left lower lateral margin (white arrow) associated with collapsed lobe, (black arrow) 1215 Poster Session l Figure 4. CT images ofdemonstrate more evident pneumothorax, the collapsed lower hing and bullae, (arrow) These bullae and blebs are not visualized on the conventional chest radiograph. Dissemination ofsilicotic nodular high densities are also clear ly visualized which are located in the middle and posterior lung regions. 1216 Poster Session 1 Figure 5. Case 4. 59 year-old, welder's lung, 2/2, s. A chest computed radiograph shows densely distributed fine irregular opacities throughout lungs and the left lung is more hyperlucent than the right. 1217 V Poster Session I Figure 6. CT images evidently demonstrate strand or streak like interstitial fibrosis, pulmonary emphysema and bullae. On the left super resolution mode images taken by 1.0 mm slice thickness clearly demonstrate impaired lung parenchyma and pulmonary vessels caused by emphysema. The presence oflarge bullae ofthe left lung posterior region shows hyperlucency on the chest radiograph. 1218 Poster Session I Figure 7. Case 5. 42 year-old, male, foundry worker's lung 2/2, s. A chest computed radiograph reveals densely distributed fine irregular opacities throughout lungs and on die left upper lung hyperlucency is noted. 1219 Poster Session I Figure 8. CT images demonstrate strand or streak like interstitial fibrosis associated with pulmonary emphysema, bullae (arrow) and honeycombing. 1220 Poster Session / A CASE CONTROL STUDY OF PNEUMOCONIOTIC COAL MINERS IN BRAZIL* EDUARDO ALGRANTI, MSc FUNDACENTRO, Sao Paulo, SP, Brazil INTRODUCTION Coalworkers' pneumoconiosis (CWP) has been known for ap proximately 150 years. It is one of the respiratory diseases which coal miners are at risk. It is generally accepted that die development of pneumoconiosis depends on a number of variables such as die amount of inhaled dust, the dust com position, the number ofyears ofexposure, the residence time ofdust in die lungs and die individual susceptibilities. Except this latter, the other factors are quantifiable, and to date there are reliable studies on the probability of acquiring CWP.6 In Brazil, it is known that dust exposure conditions in underground coal mines are critical. Moreover, the dust com position differs from that of die countries where classical studies on CWP were carried out. Brazilian coal has plenty of ashes. Only approximately 60-70% ofdie mined material is coal. Quartz concentrations are high, often above 10%,8 making us assume that CWP in Brazil is distinct from classic CWP. The high quartz content makes dose-response relations (dose = quantity of dust retained in the lungs; response = pneumoconiosis) to be not so strong since the pathogeny of classic CWP and silicosis is different. With the purpose of identifying discriminant variables be tween pneumoconiotic and oon-pneumoconiotic miners a case control study was carried out with die coal miners--studied in the Projeto Mineragao, 1984 (Mining Project--Brazil). METHODS A random sample of about 50% of the underground miners in six mines (manual, semimechanized and mechanized) was selected. The chosen miners were engaged in different underground jobs. Out of die 956 miners investigated, 816 had their radiographs read independently by three experienced readers in the ILO Radiological Classification of pneumoconiosis.5 One hundred and eight (108) radiographs were considered to be inadequate for reading. From the 708 analysed radiographs, 40 cases of pneumoconiosis (Profusion 1/0 or above) were found, and 80 cases of suspicious radiographs were detected (Profusion 0/1). For analysis the cases were divided in two groups: Group 1: Single job underground miners (pure exposure) IA) Profusion 1/0 or above (cases: 12; controls: 33). IB) Profusion 0/1 or above (cases: 37; controls: 102). Group 2: Multiple-job underground miners 2A) Profusion 1/0 or above (cases: 32; controls: 91). 2B) Profusion 0/1 or above (cases: 80; controls: 227).* 1 Supported by grant from the Brazilian Ministry ofLabour (SSMT/MTb No. 014/83). These cases were matched in the ratio of 1:3 or 1:2 based in tiie following parameters: 1. Years worked underground 1 2. Age 2 3. Control subjects with profusion 0/0 4. Non-repetitive control subjects 5. Control subjects working in the same mine. Additionally, for groups 1A and IB, we selected control sub jects performing the same job groups, i.e. supervision, face and maintenance. These matching criteria excluded 20% to 30% of the cases, due to the lack of controls or only one control. The analysed variables were cough, phlegm, breathlessness, recent acute respiratory episodes (RARE), FEV j, FVC and FEVi/FVC. Cough and/or phlegm were considered positive, when present for more than 3 months. Breathlessness was con sidered positive, if related to great efforts. The respiratory functional parameters were calculated by us ing a dry spirometer (Vitalograph, Vitalograph Limited, Buckingham, UK) and transformed into BTPS. Other data were obtained through a questionnaire on respiratory symp toms, adapted from the questionnaire on Chronic Bronchitis (MRC, UK, 1976). For calculating the differences concerning cough, phlegm, breathlessness and RARE, we used chi-squared tests from contingency tables 2x2. For FEVj, FVC, FEVi/FVC and pack years, we analysed the difference between the means through tiie Student "t" value. With both tests we rejected the null hypothesis at tiie 5% level. 1221 Poster Session I RESULTS The results are shown in Tables I and II. The mean of pack years ofthe four subgroups ofcases and controls did not dif fer significantly. In subgroup 1A, only FEVj was significant ly lower in the cases. In subgroup 2A the FVC was significant ly lower in die cases and the occurrence ofRARE was more frequent in die cases. The inclusion ofminers having radiographs 0/1 or above as cases (subgroups IB and 2B) made all the differences among the variables of cases and controls non-significant. Table I X2 Values of Contingency Table of Cases and Controls with Cough, Phlegm, Breathlessness and Recent Acute Respiratory Episodes (RARE) SUBGROUP COUGH PHLEGM BREATHLESSNESS RARE 1A 0.02 1.02 1.70 0.50 IB 0.15 0.15 0.01 1.02 2A 0.09 0.69 3.74 4.68* 2B 1.07 1.07 0.47 3-30 * p* 0.05 SUBGROUP 1A Ca Co Table n Means and Standard Deviations of Lung Function Parameters+ FEV1 FVC FEV/FVC 3.33 - 0.28"] 3-62 - 0.57J 4.21 - 0.66 4.63 - 0.79 0.80 - 0.12 0.79 - 0.11 IB ^ Co 2A Ca Co 3-69 - 0.73 3.71 * 0.67 3.44 0.59 3.72 - 0.62 4.70 t 0.78 4.67 i 0.78 4.19 0.7ll * 4.62 t 0.67J 0.79 - 0.12 0.79 - 0.11 0.82 - 0.11 0.80 ^ 0.11 2B ^ CO 3-66 ~ 0.71 3.74 - 0.66 4.59 - 0.73 4.69 - 0.75 0.80 0.11 0.81 0.09 * p $ 0.05 + The number of cases and controls are about 20% less than Table I because of rejected spyrcmetries. Ca s Cases Co = Controls 1222 DISCUSSION The studied variables were somewhat discriminating as to dif ferentiate pneumoconiotic from non-pneumoconiodc miners. The findings in die group of pure miners (FEVj) did not repeat in the multiplejob undergroup miners, who in their turn presented FVC and die occurrence of RARE different from that ofthe control. As approximately 20% ofthe lung func tion tests in the original group of 956 miners have been re jected, 1 this may have contributed to die inconsistency ofthe differences found in theFEVi and FVC ofsubgroups 1A and 2A, as miners with rejected tests (188/956), showed a significantly higher mean ofyears ofexposure than those with accepted tests (p < 0.01). The presence ofbreathlessness was nearly significant in subgroup 2A. Breathlessness, together with the number of years of exposure, FEVi/FVC, and FEVj, were die variables most closely associated with pneumoconiosis, when subgroup 2A was analysed through a probit regression analysis.1 When the suspected subjects (profusion 0/1) were included as cases there was no difference between cases and controls in both groups. This is an indirect indication that they were probably classified correctly as category 0. Respiratory symptoms are related to both dust exposure and cigarette smoking.7 The average pack years of the analyzed groups did not differ between cases and control subjects, and the effect of dust exposure was also controlled. The low capacity of discrimination presented by the variables cough and phlegm reinforces that pneumoconiosis is independent of die effects of dust on the bronchial tree.4 Autopsy studies on coal miners showed that pneumoconiosis Poster Session I did not correlate with hypertrophy of the bronchial glands, which was related to both cigarette smoking and dust exposure.2 Although case control studies are often inappropriate for con clusive analyses of the cause-effect relationships,3 especial ly when we are studying highprevalence diseases, these find ings concerning pneumoconiosis and respiratory symptoms are in accordance with classic studies on respiratory disease in coal miners. This group of miners will be followed up in 1989. REFERENCES 1. Algrami, E.: Comprometimenxo Respiratoxyo em Mineiros de Carvao de Subsolo Ativos. Relatorio Interno, FUNDACENTEO Sao Paulo (1988). 2. Douglas, A.N., Lamb, D., Ruckley, V.A.: Bronchial Gland Dimen sion in Coal Miners: Influence ofSmoking and Dust Exposure. Thorax 37:760-764 (1982). 3. Florey,C.deW.,Leeder,S.R.:MethodscfCohortStudiescfChronic Airflow Limitation. WHO Regional Publications, European Series No. 12 (1982). 4. Hyatt,R.E.,Kistin,A.D.,Mahan, T.K.:RespiratoryDiseaseinSoutheraWest VirginiaCoal Miners. Am. Rev. Resp. Dis. 89:387-401(1964). 5. International Labour Office: Guidelinesforthe Use ofILO International CUusifiaaioncfRadiographsqfPneumoconiosis. Revised Edition 1980. Occupational Safety and Health Series No. 22. Geneve (1980). 6. Jacobsen, M.: Dust Exposure and Pneumoconiosis at 10 British Coal Mines, pp. 99-107. Wth International Pneumoconiosis Conference, Caracas, 1978. Bremerhaveo (1985). 7. Morgan, W.K.C.: Industrial Bronchitis. Br. J. bid. Med. 35:285-291 (1978). 8. Valenti, F.I.: Izvantamentodas Condigdesde Seguran&ie Wgie nedas btdustrias Carboniferas, SC. Relatorio Intemo, FUNDACENTRO, Sao Paulo (1986). 1223