Document 3Gnz8LaMv4vB6g5JgXLQwpDy

Pulmonary Changes among Vinyl Chloride Polymerization Workers* R. Lilis, At.D.; II. Anderson, M.D.; A. Miller, M.D.; and I. J. Selikoff, M.D. Soon after the emergence of vinyl chloride as a new and potent carcinogen, producing hemangiosarcoma of the liver, clinical studies of three groups of exposed workers were undertaken in order to assess the preva lence of vinyl chloride-induced adverse health effects. The spectrum of clinical and laboratory tests was broad.1 with the main focus on a possible hepatotoxic effect and/or portal hypertension, on the abnormalities of peripheral circulation of the extremities with possible associated bone lesions in the distal phalanges (acroosteolysis), and on the history of prenarcotic symptoms during overexposure. In the absence of appropriate VC measurements in the past, such acute episodes were interpreted as reflecting significant toxic exposure. Methods Chest x-ray films were included in the examination proto col, as a routine procedure, as was a complete smoking history and the chrome bronchitis questionnaire. Pulmonary function tests were also included.2 A Systems Research Lab oratories predictive pulmonary screener was used for spirom etry and a Vertek 3500 Fleisch pneumotachygraph for ob taining flow volume curves. At the time this study was undertaken, there were only a few reports in the literature of lung changes in PVC workers. One case of pneumoconiosis in a 30-year-old worker who had inhaled PVC dust had been reported.3 The lung biopsy had shown granulomatous lesions (foreign body type) to be present. Fibrotic lung changes and altered pulmonary func tion tests had been reported in 96 workers exposed to polyvinyl chloride dust; the changes were more pronounced in persons with long exposure.4 While all three groups of workers had been active in PVC polymerization facilities (vinyl chloride and polyvinyl chloride exposure), there were obvious differences insofar as the degree and pattern of exposure were concerned. The first plant (Group A) was characterized by a very uniform and constant technology, consisting only of the polymerization of vinyl chloride to polyvinyl chloride. VC exposure levels had been significantly elevated in the past, to the point that most of the examined workers had experienced repeated episodes of prenarcotic symptoms, especially during the reactor clean ing operation. PVC dust had also been abundant, especially in the bagging area. Most of the workers started their activity in tin's area, and there was no adequate enclosure of the area, so that the entire examined group was practically exposed to vinyl chloride and polyvinyl chloride dust. The second plant (Croup B) was studied because it was the first PVC polymerization facility, so that long exposure effects could be expected. While VC and PVC exposure levels had probably been of the same order as in the first plant in the past, the diversification of the technology intro ducing copolymers (with vinyl acetate, vinylidene chloride, acrylonitrile) with a relatively low component of vinyl chloride, and the relocation of some production lines in new "From Mount Sinai School of Medicine, New York City. CHEST, 69: 2, FEBRUARY, 1976 SUPPLEMENT Table 1---- Chest X-ray Film Abnormalities in VC-l*VC Exposed Workers (Croup A)* Duration of Exposure (years) Total No. Examined ,------------------- *---------------- Abnormal Chest X-ray Number Percent /fju-/' /) r,.s- XI V v. < Less than 2 48 7 14.6 2.1-5 fifi 12 18.2 5.1-10 54 8 14.8 10.1-20 81 27 33.3" 20.1 -- 41 12 30.0" Total 290 G6 22.7 `After exclusion of all persons with any past asbestos, silica or coal dust exposure. "Chi'test showed the difference in prevalence of chest x-ray abnormalities in workers with exposure of more than 10 years to be significantly higher than in those with shorter exposure. buildings, with modem equipment, had led to a decrease of exposure levels in recent years, for both VC and PVC. The third plant (Group C) was studied because it was known that industrial hygiene surveys and monitoring of the VC exposure levels had made it possible to achieve a relative ly low exposure level. A panel of five physicians read the chest x-rays. For statistical reporting, a consensus reading was used. The chest x-ray films were read after the completion of each clinical survey. Information on age, job (degree of exposure), length of exposure or any other specifics were not known at the time the x-ray films were read. The only data available to the readers were identification by study number and name. After the completion of the chest x-ray readings, special attention was given to any other possible occupational expo sure which may be associated with abnormal findings. The complete occupational histories, taking into account previous jobs, make it possible to exclude from this analysis all cases in which there had been any asbestos ((even slight), silica or coal dust exposure. Most of these cases were clustered in the B group, the plant being located in the vicinity of a coal mining area (West Virginia). Results The finding of linear reticular, and less often nodular. Tabic 2--Chest X-ray Abnormalities in VC-PVC Exposed Workers (Group B)* Current Exposure Past Exposure Duration of Total Abnormal Total Abnormal Exposure No. Chest X-ray No. Chest X-ray (years) Examined No. % Examined No. % Less than 2 2.1-10 10.1-20 20.1--- 22 39 22 74 3 13.6 5 13 5 22.7 15 20.3 12 35 15 31 2 16.6 9 25.7 3 20 5 16.1 Total 157 28 17.8 93 19 20.4 `After excluding all persons with past asbestos, silica or coal dust exposure. "Chi* test showed the difference in prevalence of chest x-ray abnormalities in workers with current, exposure of more than 10 years to be significantly higher than in those with shorter exposure. 18TH ASPEN CONFERENCE 299 N & S 00 o o opacities on significant numbers of the VC-PVG exposed workers' chest x-ray films in the first examined group alerted us to the problem (Group A--Table 1). In the absence of a uniform system for classification of chest xray abnormality of this t\pe (linear, reticular or rounded opacities) the ILO U/C Pneumoconiosis Classification was used. All readers were experienced in the use of this system. The analysis showed a definite increase of x-ray changes with length of exposure; the prevalence was significantly more elevated in workers with more than ten years of VC-PVC exposure as compared to those with shorter exposure time. The overall prevalence of small linear reticular and/or rounded opacities was 22.7 per cent in this group. In the second examined group (Group B--Table 2), where there had been a more diversified pattern of VCPVC exposure, with probably a lower level of recent VCPVC exposure, but with more workers who had been active in the department for ox er 20 years, some interest ing relationships were found. In workers with current VC-PVC exposure there was again a definite, statistically significant increase in preva lence of the chest x-ray abnormalities with duration of VC-PVC exposure. In separating a subgroup of workers who had worked in the PVC polymerization process in the past, but had since moved to other departments, no relationship with length of exposure was found, but the overall prevalence for this subgroup (past exposure) was slightly more elevated than in the workers with current exposure, probably reflecting the effect of higher levels of exposure in the past. For the entire Group B the prevalence of chest x-ray changes (small linear reticular and/or rounded opaci ties) was 19.4 percent, somewhat lower (but not statis tically significant) than in Group A. It is of interest to emphasize at this point that there was a difference in age distribution between the two mentioned groups; Group A (with the higher prevalence of chest x-ray changes) being significantly younger than Croup B. The third examined group (Croup C) was found to have a much lower prevalence of chest x-ray abnormali ties (Table 3). The overall prevalence of 4.3 percent (19 Table 3-----Chest X-ray Abnormalities in VC-PVC Exposed Workers (Group C)* Abnormal Chest X-ray Total No. Examined 445 No. 19 % 4.3 Table 4-----Chest X-ray Abnormalities in Three Different VC-PVC Plants Group A B C Total No. 'Examined 290 250 445 Abnormal Chest X-ray No. % 66 22.7 46 19.4 19 4.3 300 18TH ASPEN CONFERENCE workers out of 445 examined) made any further aiial\MV irrelevant. Plant C was known to have had relatively lu levels of exposure to VC for the last 15 years, when continuous monitoring system had been instituted. In evaluating the prevalence of chest x-ray abnonn.dities in VC-PVC exposed workers in the three mentioned plants (Table 4), two main trends can be identified. First, in the two groups (A and B), where there was ,, relatively high prevalence of such abnormalities, there was a statistically significant increase with duration u| exposure. Second, in comparing the results in the three examined groups, the highest prevalence of chest x-r.u changes is found in the plant with highest exposme levels, while the lowest prevalence characterizes workers from the plant with known relatively low exposure levels. Since the finding of small linear-reticular and ur nodular opacities in VC-PVC exposed workers warather unexpected and no pathogenic explanation a.is yet available to suggest an interpretation, several other factors which may have had some relationship to the findings were considered. Smoking histories had been carefully taken and the ov rail prevalence of a positive smoking history w.istrikingly similar in the three examined groups (Croup A--75 percent. Group B--75.2 percent and Group ( --74.6 percent). The prevalence of positive smokii.c history was found to be higher in workers with abnorio , chest x-ray films, in both Group A and B (Tables 5 at id 6). The prevalence of positive smoking history in work ers with abnormal chest x-ray films was statistical!} significantly higher in both groups. This could indicate i Table 5---Chest X-ray Abnormalities of VC-PVC Exposed Workers and Smoking History (Group A) Normal Chest X-ray Abnormal Chest X-ray Positive Positive Total No. Smoking History Total No. Smoking History No. % No. % 224 161* 72 66 57* 86 `Prevalence of positive smoking history significantly higher among workers with abnormal chest x-ray (Chi' = 5.734; 0.01 <P <0.02). Table 6--Chest X-ray Abnormalities of VC-PVC Exposed Workers and Smoking History (Group B) Normal Chest X-ray Abnormal Chest X-ray Positive Total No. Smokinga History Total No. No. % Positive Smoking History No. % 203 151" 74 47 42" S9 (71)* (35) (12)* (25.6) `Figures in parenthesis--ex-smokers. "Prevalence of positive smoking history was significantly higher in workers with abnormal chest x-ray than in those with normal chest x-ray (Chi' = 4.864; 0.02 <P <0.05). CHEST, 69; 2, FEBRUARY, 1976 SUPPLEMENT I li S' tl C o Table 7-- Workers anti Chest X-ra\ Normal Abnormal Total Prevalence chest x-ray chest x-ra> Table 8--( Workers at Chest X-m Normal Abnormal Total * Prevail':-. the work those wi' multiple Chron criteria, percent percent older ai practica In ai chitis a though somew) differei cant (1 Fins norma tion of durath age, tl 10). " ages i comp when and r This In chest er tl abut not: retie wor CHE Tiiljlc 7--Chest X-ray Changes in VC-PVC Exposed Workers and Chronic Bronchitis (by History), (Group A) Chronic Bronchitis by History Chest X-ray Normal Total No. 224 No. 41* % 18.3 Abnormal G6 18* 27.2 Total 290 59 20.4 Prevalence of chronic bronchitis in workers with abnormal chest x-ray not significantly different from those with normal chest x-ray. Table 8--Chest X-ray Abnormalities of VC-PVC Exposed Workers and Chronic Bronchitis (by History), (Group B) Chronic Bronchitis by History Chest X-ray Normal Abnormal Total No. 203 47 No. 31* 9* % 15.3 19.2 Total 250 40 16.0 Prevalence of chronic bronchitis not significantly different in the workers with abnormal chest x-rays, as compared to those with normal chest x-ray. multiple factor effect of smoking and VC-PVC exposure. Chronic bronchitis, by history, according to the MRC criteria, was found with an overall prevalence of 20.4 percent in Group A (highest exposure) and of 16.0 percent in Group B, although Group B was significantly older and smoking habits, as mentioned above, were practically identical. In analyzing the relationship between chronic bron chitis and chest x-ray findings it was found that, al though workers with abnormal chest x-ray films had a somewhat higher prevalence of chronic bronchitis, the difference, in both groups, was not statistically signifi cant (Tables 7 and 8). Finally, since a higher prevalence of chest x-ray ab normalities was found among workers with longer dura tion of exposure (more than ten years), and since longer duration of exposure generally is associated with older age, the age factor was also looked into (Tables 9 and 10). There was no significant difference between mean ages of workers with abnormal chest x-ray findings as compared to those with normal chest x-ray film findings, when considering the groups with less than ten years and more than ten years' duration of VC-PVC exposure. This was so for both Group A and Group B. In addition, the group with the higher prevalence of chest x-ray changes (Group A) was significantly young er than the group with the lower prevalence of such abnormalities. These findings would indicate that age is riot an important factor in the appearance of small linearreticular or rounded opacities in VC-PVC exposed workers. CHEST, 69: 2, FEBRUARY, 1976 SUPPLEMENT Table 9---Abnormal Chest X-ray in VC-PVC Exposed Workers (Group A) Duration of Exposure (years) Normal Abnormal Chest X-ray Chest X-ray Total I.css than 10 yrs 31.36* 9.7 34.33* 9.3 31.9 10.1 More than 10 yrs 44.98* 8.9 46.9* 9.4 45.4 8.9 Mean age of workers with abnormal chest x-ray films not significantly different from-those with normal chest x-ray, in the less than 10 years exposure group as well as in the more than 10 years exposure group. Table 10--Abnormal Chest X-ray in VC-PVC Exposed Workers (Group B) Duration of Exposure Normal Abnormal Chest X-ray Chest X-ray Total Less than 10 yrs 48.03* 7.5 49.4* 5.69 48.2 9.9 More than 10 yrs 55.3* 7.8 55.7* 5.1 55.7 6.0 Mean age of workers with abnormal chest x-ray films not significantly different from those with normal chest x-ray, in the less than 10 years exposure group as well as in the more than 10 years exposure group. The pulmonary function tests showed a relatively high prevalence of obstructive changes. FEV,/FVC was re duced (less than 75 percent) in 43.4 percent of all examined workers in Croup A and 46 percent of those in Group B (Tables 11 and 12). FEV, percent of predicted was reduced in smaller proportions of all considered groups; this may be due to Tabic 11--Screening Pulmonary Function Tests as Related to Length of Exposure (Plant A) FEV,% of FVC % of FEV./FVC Predicted Predicted Duration of Total No. <75% <80% <80% Exposure Examined No. % No. % No. % Less than 10 years 168 63 37.5 26 16 14 8 More than 10 years 122 63 52 27 23 13 10.6 Total 290 126 43.4 53 18.2 27 9.3 Table 12--Screening Pulmonary Function Tests as Related to Length of Exposure (Plant B) FEV,% of FVC % of FEVi/FVC Predicted Predicted Duration of Total No. <75% <80% <80% Exposure Examined No. % No. % No. % Less than 10 years 108 43 39.8 12 11 1 0.9 More than 10 years 145 73 50.3 19 13.1 5 3.4 Total 253 116 46 31 12.3 6 2.3 18TH ASPEN CONFERENCE 301 60Q2LZZZ 1 t: Table 13--Chest X-rny Changes and Pulmonary Function (Plant A) N'ormal x-rays Abnormal x-rays *FEV,/FVC<74% % Fred FEV, <79% % Pred FVC<79% 1 or More Abnormal PFT* Total 222 t8 No. 105 38 % 47.3 55.9 Table 14---- Chest X-ray Changes and Pulmonary Function (Plant B) Normal x-rays Abnormal x-rays *FEV,/FVC<74% %Prcd FEV, <79% % Pred FVC<79% 1 or More Abnormal PFT* Total 207 46 No. 98 23 % 47.3 50 the fact that the vital capacity was higher than 100 percent of predicted in one-third of workers. The preva lence of decreased FEV, percent of predicted was high er in Group A (although this group was younger) and in this group there was also- an increase in prevalence of tliis abnormality with length of exposure. A decrease of FEV, percent of predicted may indicate a more ad vanced abnormality than the reduction of FEV,/FVC, and may reflect the specific effect of VC-PVC exposure more accurately. A restrictive pattern was found in 9.3 percent of Group A and in only 2.3 percent of Group B. Again, it has to be remembered that Group A was significantly younger. An attempt to evaluate possible correlations between chest x-ray changes and pulmonary function abnormali ties did not show any consistent link (Tables 13 and 14). While pulmonary function abnormalities' were slightly more prevalent in workers with abnormal chest xray film findings, the differences when compared to those with normal chest x-ray films were small, in both groups A and B, Smoking and age are both related to obstructive pul monary function changes and, under such circumstances it appears difficult to isolate the specific effect of occupa tional VC and PVC exposure, although the prevalence of these changes is striking. It is conceivable that chest x-ray changes and obstruc tive pulmonary function abnormalities reflect different pathologic processes, the chest x-ray changes being mainly related to parenchymal damage, while the ob structive pulmonary function changes would reflect air way changes. Discussion The problem of pulmonary changes developing after 302 18TH ASPEN CONFERENCE VC-PVC exposure has many implications. First, the pos sibility of a pathogenic similarity to other VC-iiulnml abnormalities arises. Periportal and capsular fibrosis of the liver, peripheral vascular changes, including K.,\. naud's syndrome, but also thickening of the arteriolar wall and even complete occlusion of small vessels ii, some cases, scleroderma-like skin changes with marked increase in collagen formation have all been well docu mented in VC-exposed workers. The sequence of events at the cellular and subcellular level is not yet compleleh understood, but such mechanisms may be active in ii>,. pulmonary tissue as well. The number of published reports on VC-PVC induced adverse health effects has markedly increased over tin* last year, and there were several more, beside those mentioned in the introductory remarks, pointing to pul monary changes due to VC-PVC exposure. Weginair* reported fine nodular changes on the chest x-ray films nt three workers out of 37 in a PVC processing plant (PW exposure only). Berk et al8 found, in a 30-year-old man who had been exposed for eight years, and had charac teristic VC induced liver damage, significant restricts o pulmonary disease (forced vital capacity--70 percent of predicted). Prodan and co-workers found in guinea pigs exposed to vinyl chloride (10 percent) over a threvmonth period, interstitial infiltration, elevated neutral mucopolysaccharides in the alveolar walls, marked pul monary fibrosis with well organized connective tissue. Frongia and co-workers3 reported on pathologic changes in guinea pigs and rats exposed 24 hours a day. from two to seven months, to inhalation of PVC dust in the bagging area of a plant. In guinea pigs they found an initial alveolo-lobular macrophagic reaction, with multinucleated giant cells, and with very fine granules in the cytoplasm, which were unchanged by usual coloring techniques. After longer exposure (seven months) granuloma-like foci were identified while the initial alveolar reaction was fading out. In rats there was much less alveolar reaction, but marked thickening of the septa due to histio-macrophagic infiltration was prominent; after seven months, the same granuloma-like changes as in guinea pigs became dominant. A pathology survey of lung slides from deceased VCPVC workers is now in progress in our department, and lung specimens from VC-exposed animals are also reviewed. Pulmonary changes in VC-PVC exposed workers are also of interest from another viewpoint. Waxweiller et a!,< in a recent mortality study on VC polymerization workers, found an excess in the mortality due to respira tory cancer (SMR -- 156). There was some indication that the large cell undifferentiated type was more preva lent than expected. The same study also Found an excess mortality due to "other respiratory diseases" (SMR = 176). For all these reasons an awareness of the possible lung damage due to VC-PVC exposure is necessary; the pur pose of this presentation was to contribute to such a goal. 1 Szcm caus< I-avr 2 Wcg gien. chin 197; 3 Froi sper ah n 342 4 Wa pla? 10. Lun Chr of < .Vnrg an/11 the* post of o mer pro! the dan pre< tota voli sect ton anc Clc fur fur am pa sp< till alii Sill nI . CjO o CHEST, 69; 2, FEBRUARY, 1976 SUPPLEMENT References 1 Szcndc B, Lapid R, Neines A, et al: Pneumoconiosis caused by the inhalation of polyvinyl chloride dust. Med Lavoro 6 1:433, 1970 2 Wegman D: (Massachusetts Division of Occupational Hy giene, Boston) Discussion: Further results: in polyvinyl chloride production workers. Ann NV Acad Sci 246:18-21, 1975 3 FYongia N, Spinazzola A, Bucarclli A: Lesioni polmonari sperimentali da inalazionc prolungata di polveri di PVC in abmientc di lavoro. La Medicina del Lavoro 65(9-10) :321342, Sept-Oct, 1974 4 Waxweiler RJ, Stringer W, Falk H, et al: NIOSH, Xeoplastic lisk among vinyl chloride polymerization worker. 116, 1975 (Occupational Carcinogenesis Meeting). Lung Function Profiles in the Chrysotile Asbestos Mines and Mills of Quebec* Margaret ft. Beeklake, M.D.; Gisele Foumier-Massey, M.D.; and Robert Black, M.D. TJ ecause of a clinical impression that it was not un*-' common to find lung function profiles other than the classic restrictive one associated with asbestos ex posure, we defined the lung function profiles in a sample of over 1,000 Quebec chrysotile asbestos workers. These men had been examined in 1967-68 as part of a com prehensive study of the effects of exposure to asbestos in the chrysotile mines and mills of Quebec.1'1 Five stan dard tests of lung function, expressed as a percent of predicted, were used to establish the function profiles: utal lung capacity, residual volume, forced expiratory volume in 0.75 second, forced expiratory volume in 1 ccond/forced vital capacity, and maximal mid-expiraory flow rate.3 Results were related to dust exposure1 md smoking and have been described in full elsewhere.3 llose to half the men (44.3 percent) had normal lung inction profiles and a further 26.5 percent had minor motion changes only. Among the remainder, restrictive nd obstructive function profiles occurred with cornarable frequency (12.8 percent and 12.2 percent repectively). Both svere associated with radiologic feaires of asbestosis; both occurred infrequently in the bsence of the smoking habit (Table 1.) These findings iggest an association between the smoking habit and ie development of an asbestos-related fibrosis in so far this is reflected in a restrictive function profile. In From the Department of Epidemiology and Health, McGill University, Montreal, and lUniversite de Sherbrooke, Sherirooke, Quebec, Canada. Supported by the MRC (Canada) and the Institute of Ocupational ami Environmental Health of the Quebec Asbes'js Mining Association. C. Foumier-Massey held an MRC ellowship; M. R. Becklake is an Associate of the MRC. EST, 69: 2, FEBRUARY, 1976 SUPPLEMENT Tabic 1--Effects of Chrysotile Exposure on the Health of 1015 Current Quebec Asbestos Workers* Oust fn<lex** ' >10 10- 100- 200- 100- 800- Non-Smokers Prevalence %t a) chronic bronchitis 10 b) dyspnea 0 Function profile--t prevalence % restrictive 3 obstructive 0 % age fall in function t VC 0 FEV, 0 Deo., rest 0 exercise 0 19 14 3 1 -10 -9 -11 -8 t9 24 3 0 -16 -9 -15 -9 46 31 l -- -IS -13 -18 -18 21 13 l -- -19 -15 -12 -18 49 44 1 -- -23 -22 -15 -20 Smokers Prevalence %f a) chronic bronchitis 23 22 30 29 46 45 b) dyspnea 4 15 18 21 30 32 Function profile--% prevalence % restrictive 8 14 16 10 4 13 obstructive 12 12 13 12 23 12 % age fall in functionf VC 0 -3 -7 -10 -13 -14 FEVl 0 -3 -8 -10 -15 -15 Deo., rest 0 +4 +3 +5 -3 0 exercise 0 0 -2 0 -5 -7 `For all measurements, prevalence % has been age-standard ized to the total working population as of October 31st, 1966. This was to allow for the smaller number of men for whom function profiles were analyzed. *`Expressed in million particles per cubic foot years! (Based on a total sample of 1,015 men*, ** tBased on 995 men) addition, the data provided some indirect evidence based on a principal component analysis3 that in those Quebec asbestos workers who smoke, the character of the dust-associated function impairment might be either obstructive or restrictive. Further studies are required to establish the extent to which this experience in the primary mining and milling of chrysotile asbestos is directly applicable to secondary industries concerned with the further processing of this fiber. References 1 Beeklake MR, Fournier-Massey C, Rossiter CE, et al: lung function in chrysotile asbestos mine and mill workers of Quebec. Arch Environ Health 24:401, 1972 2 McDonald JC, Beeklake MR, Gibbs GW, et al: The health of chrysotile asbestos mine and mill workers of Quebec. Arch Environ Health 28:61, 1974 3 Fournier-Massey G, Beeklake MR: Pulmonary function profiles in Quebec asbestos workers. Bull Physio-pathologie Resp 11:429, 1975 4 Gibbs GW, Lachance M: Dust exposure in the chrysotile asbestos mines and mills of Quebec. Arch Environ Health 24:189, 1972 18TH ASPEN CONFERENCE 303 22273005 i