Document JNoD4MM6gML6VJ0dwbVe91X8O

Pulmonary Changes among Vinyl Chloride Polymerization Workers* H Lilts, M.D.. H. Anderson, M.D.; A. Miller, M.D.; and I I Sclikoff, M.D Scon 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 oread.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 (aeroosteolysis), 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 it routine procedure, as was a complete smoking history and the chronic bronchitis i|uestionnaire. Pulmonary function tests were also included.a A Systems Research Lab oratories predictive pulmonary screener was used for spirom etry and a Vertek 3500 Fleisch pneumotachygraph for ob taining Sou' volume curves. At the time this study was undertaken, there were only a few reports m 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 ail three groups of workers had been active in PVC polymerization facility (vinyl chloride and polyvinyl hl'iride exposure!, then were obvious differences insofar as the degree and pattern uf 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 this area, and there was no adequate enclosure of the area, so that die entire examined group was practically exposed to vinyl chloride and polyvinsl chloride dust. The second plant (Group B) was studied because it was the first PVC polymerization Ijeilitx. so that long exposure effects could be expected. While VC and PVC exposure lei els has! probably been of the same order as in the first in 'he past, the diversification ol the technology intro* .ivuog ci .p- >lx nierx i v>, \ni\I acetate, xinyhertie chloride, acrylonit'ile ) with a reLtixek low component ol vine! cl liirule. and the relocation of some production lire x in new 'From Yount Sinai School of Medicine, \ew Ymk Cits Table 1---- Chest X-ray Film ihnormalities in yc-rrc Exposed Workers (Croup A)' Duration of Exposure (years) Total No. Examined Iz--s than 2 2.1-5 5.1-10 10.1-20 20 1 -- 48 66 54 81 41 Abnormal Chest X-rav Number Percent 7 14,6 12 18 2 8 14 8 27 33 3** 12 30.0** Total 290 66 22.7 'After exclusion of all persons with any past asbestos, silica or coal dust exposure. 'Chi'test showed the difference in prevalenee 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 (Croup C) was studied liecause it was known that industrial hygiene surveys and monitoring of the VC exposure levels had made it possible to achiex e a relative ly !n\x exposure level. A panel of fixe 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 surxev. 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 ax.(liable to the readers were identification by study numlier and name. After the completion of the ohest x-ray readings, special attention was given to any other possible occupational expo sure which may be associated xx-ith abnormal findings. The complete occupational histories, taking into account previous jobs, make it possible to exclude from this analysis all cases in xxhich 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, Table 2--Chest X-ray Abnormalities in VC-PEC Exposed Workers (Group B)m Current Kxposure Past Exp isuro Duration of Total Abnormal Total Abnormal Exposure No. Chest X-ray No. Che-A X-rav (years) Examined No. c*c Examined No. C rr Less than 2 2 1-10 HI 1-20 20 l-~* 22 39 22 74 3 13.6 5 13 5 2 7 15 20.3 12 35 15 31 o 166 25 7 3 20 5 16 1 lota! 157 28 17.8 93 19 20 4 "After exe lading all per.-ons xxith pasi s-'m- StOJ-, silica or coal iu>t exposure. Chi lest -hoxve.l the dlffe n-Mcc in prevalent * of i hest x-ray nl 'h< ii tnal iUi-m m workers with i urrcht \|m eoirc of more I)11111 10 year* to l>c simuh cunt is IiiltImt t It.Ill in il lO-e With -boiler expo-lire CHEST, 69- 2. FEBRUARY. 1976 SUPPLEMENT 18TH ASPEN CONFERENCE 299 Opacities on significant numbers of the VC-PVC exposed ' workers' chest x-ray films in the first examined group alerted us to the problem (Croup A--Table 1). In the absence of a uniform system for classification of chest xray abnormality of this type (linear, reticular or rounded opacities} the ILO U/C Pneumoconiosis Classification was used. (U1 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 (Croup 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 over 20 year.*, 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 Croup B the prevalence of chest x-ray changes (small linear reticular and/or rounded opaci ties) was 19.4 percent, somewhat lower (but fjot 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 (Group 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--Cheat X-ray Abnormalities in VC-PVC Exposed Workers (Croup C)* Abnormal Chest X-ray Total No. Examined 445 No. 19 % 43 Table 4--Chest X-ray Abnormalities in Three Different VC-PVC Plants Group \ B c` Total No Examined 200 250 ll'i Abnormal Chest X-ray No. r~c (Wi 22 7 46 10.4 I!) 4 3 300 18TH ASPEN CONFERENCE workers out of 445 examined) made any further analysis irrelevant. Plant C was known to have had relatively low levels of exposure to VC for the last 15 years, when a continuous monitoring system had been instituted. In evaluating the prevalence of chest x-ray abnormali ties 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 of exposure. Second, in comparing the results in the three examined groups, the highest prevalence of chest x-ray changes is found in the plant with highest exposure levels, while the lowest prevalence characterizes workers from the plant with known relatively low exposure levels. Since the finding of small linear-reticular and/or nodular opacities in VC-PVC exposed workers was rather unexpected and no pathogenic explanation was 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 was str.kingly similar in the three examined groups (Group A--75 percent. Croup B--75.2 percent and Group C --74.6 percent). The prevalence of positive smoking | history was found to be higher in workers with abnormal chest x-ray films, in both Group A and B (Tables 5 and 6). The prevalence of positive smoking history in work ers with abnormal chest x-ray films was statistically ! significantly higher in both groups. This could indicate a Table Sy--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. <7C 224 161* 72 66 No. % r. 57' 86 Prevalence of positive smoking history significantly higher among workers with abnormal chest x-ray (Chi* ----5.734; 0 01 <P <0.021. ' 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 Positive Total No. Smoking History Total No. Smoking History No. No. % 203 151 * 74 (711* 135. 47 42** (I2i* 89 (25.6) 'Iigiii. - in pnroni In--is o\-sinokors, "Prevalence of positive smoking history was significantly higher in workers with nliiiortital chest x-ray than in those wit h normal chest x-ray '('in3 -- 4.N04 ; 0.02 < P <0.05). CHEST, 69: 2. FEBRUARY. 1976 SUPPLEMENT Tali! Worker- i Chest N Normal Ahnorn Total *Preva! chest ' chest Table 1 Worki Chest Norm; Abnor Total Prev the thos. multi Cl critei ' pern . perci oldei prat- In chiti thou som difft cant F non tion dur. age 10) age cor wh am Tli cb er ab n< rc u Cl DTH 000042430 / Table 7--Chest X-ray Changes in VC-PVC Expored Workers and Chronic Bronchitic (by History), (Group A) Chest X-ray Total No. Chronic Bronchitis by History r No. % * Normal 224 41* 18.3 Abnormal 66 18* 27.2 Total 290 59 20.4 Prevalence of rhrnnir bronchitis in workers with ttlmormul chest x-ruy not significantly different from those with normal chest x-ray. Table 8--Chert X-ray Abnormalities of VC-PVC Ex pored Workert and Chronic Bronchitic (by History), (Group B) Chronic Brohrhitis by History Chest X-ray Total No. No. % Normal 203 31* 15.3 Abnormal 47 9* 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 l>oth 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 normai 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 Croup B. In addition, the group with the higher prevalence of chest x-ray changes (Croup A) was significant!) yoimg- i!..iii tin gnnip 'Mlii the lower prevalence ol such abnormalities. These findings would indicate that age is not an impoilant 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 Less than 10 vrs 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 froire those with normal chest x-ray, in the less than It) years exposure group as well aa 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 "n 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 f prevalence of obstructive changes. FEV,/FVC was re duced (less than 75 percent) in 43.4 percent of all examined workers in Group A. and 46 percent of those in sGroup B (Tables 11 and 12). FEV, "percent of predicted xvas reduced in "smaller proportions of all considered groups; this may be due to Table 11--Screening Pulmonary Function Tests as Belated to Length of Exposure (Plant A) Durationof Total No. Exposure Examined FEVi/FVC <75% No. % FEV,% of Predicted <80% No. % FVC % of Predicted <80% No. % Iyens 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) Duration of Total No. KxfxiMirp Examined FEV,% of FEV,/FVC' Predicted <75', <so'; N<. % N o. ; FVC % of Predicted <80% No. % D'ss than M> IOK ih ;ik 12 11 1 0.5) Morr t han l*i \ t\-ir> 1 15 73 50.3 19 III 5 3.4 Total 1 Hi Hi HI I2.H 6 2.3 18TH ASPEN CONFERENCE 301 DTH 000042431 Table 13--Chet! X-ray Change* and Pulmonary Function (Plant A) 1 Normal'*x-rav* a Abnormal x-raya *FEV,/FVC<74% % Pred FEV, <79% % Pred FVC<79% 1 or More Abnormal PFT* Tota) 222 68 No. 105 38 % 47.3 55.9 Table 14--Chest X-rar Change* and Pulmonary Function (Plant B) Normal x-raya Abnormal x-raya *FEV,/FVC<74% %Pred FEV, <79% % Pred FVC<79% Total 207 46 1 or More Abnormal PFT* No. C/C7 98 47.3 23 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 this 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 rememliered that Croup 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 x- ray 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. Discvssion 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-induced abnormalities arises. Periportal and capsular fibrosis of the liver, peripheral vascular changes, including Ray naud's syndrome, but also thickening of the arteriolar wall and even complete occlusion of small_ vessels ia some cases, scleroderma-like skin changes with marked increase in collagen formation have all been well docu 1 Szei cau: Lav i We giei ' chU mented in VC-exposed workers. The sequence of events at the cellular and subcellular level is not yet completely understood, but such mechanisms may be active in the ' c pulmonary tissue as well. The number of published reports on VC-PVC induced adverse health effects has markedly increased over the last year, and there were several more, beside those mentioned in the introductory remarks, pointing to puk ' monary changes due to VC-PVC exposure. Wegman* 3 Fro spe i abr '. 34 4 Wa pla ( 16, reported fine nodular changes on the chest x-ray films of' < three workers out of 37 in a PVC processing plant (PVC exposure only). Berk et al* found, in a 30-year-old man ^ who had been exposed for eight years, and had charao- ? Lun teristic VC induced liver damage, significant restrictive * pulmonary disease (forced vital capacity--70 percent of predicted). Prodan and co-workers found in guinea pigs Chr of ' exposed to vinyl chloride (10 percent) over a three-\V o "*. month period, interstitial infiltration, elevated neutral S1:. Mart mucopolysaccharides in the alveolar walk, marked puk and i monary fibrosis with well organized connective tissue. Frongia and co-workers3- reported on pathologic v, changes in guinea pigs and rats exposed 24 hours a day, ? B from two to seven months, to inhalation of PVC dust in - the the bagging area of a plant. In guinea pigs they found an -- posu initial alveolo-lobular macrophagic reaction, with multi- I. of o> nucleated giant cells, and with very fine granules in the men cytoplasm, which were unchanged by usual coloring.-, techniques. After longer exposure (seven months) * * '. preh the granuloma-like foci were identified while the initial. dart alveolar reaction was fading out. In rats there was mud) v t ;pre< less alveolar reaction, but marked thickening of the septa tota due to histio-macrophagic infiltration was prominent; volu after seven months, the same granuloma-like changes as iseco in guinea pigs became dominant. ^ -ri ton A pathology surv ey of lung slides from deceased VCPVC workers is now in progress in our department, and lung specimens from VC-exposed animals are also ! and I'Clo- 1 fun' reviewed. fun< 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 = : :i- I and par spe tui< .'! abs sue the as 176). Fur 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 eontrilnite to such a goal. CHEST, 69: 2, FEBRUARY. 1976 SUPPLEMENT F .Hi l In % S' Cl ;J! t. 1 <jl'' `f $` CH DTH 00004243:3 r References 1 Szende B, Lapid K, Nemes A, et al: Pneumoconiosis caused by the inhalation of polyvinyl chloride dust. Med Table 1--Effect* of Chrvsotile Exposure on the Health of 1015 Current Quebec Asbestos Workers' Dust Index** >10 10- 100- 200- 400- 800- Lavoro 61:433, 1970 2 Wegman D: (Mjissachusetts Division of Occupational Hy giene, Boston) Discussion: Further results in polyvinyl chloride production workers. Ann NY Acad Sci 246:18-21, 1975 3 Frongia N, Spinazzola A, Bucarelli A: Lesioni polmonari sperimentali da inalazione prolungata di polveri di PVC in abmiente di lavoro. La Medicina del Lavoro 65(9-10) .321342, Sept-Oct, 1974 4 Waxweiler RJ, Stringer W, Falk H, et al: NIOSH, Neo plastic risk among vinyl chloride polymerization worker. 116, 1975 (Occupational Carcinogenesis Meeting). Lung Function Profiles in the Chrysotile Asbestos Mines and Mills of Quebec* > Margaret R: Becklake, Sl.D.; Cisele Fournier-Massey, M.D.; and Robert Black, M.D. Non-Smokers Prevalence %f a) chronic bronchitis 10 19 19 46 21 49 b) dyspnea 0 14 24 31 13 44 Function profile--J prevalence % restrictive 3331 1 1 obstructive 0 1 0 --' -- -- % age fall in function! VC 0 -10 -16 -18 -19 -23 FEV, 0 -9 -9 -13 -15 -22 Dro- rest 0 -11 -15 -18 -12 -15 exercise 0 -8 -9 -18 -18 -20 Smokers Prevalence %t a) chronic bronchitis 23 22 30 29 46 45 b) dyspnea 4 15 18 21 30 32 Function profile--t prevalence % restrictive < 8 14 16 10 4 - 13 obstructive 12 12 13 12 23 12 % age fall in function! VC 0 -3 -7 -10 -13 -14 FEV1 0 -3 -8 -10 -15 -15 Deo., rest 0 +4 +3 +5 -3 0 exercise 0 0 -2 0 -5 -7 Because 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 sampje 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 df exposure to asbestos in the chrysotile mines and mills of Quebec.1-5 Five stan dard tests of lung function, expressed as a percent of predicted, were used to establish the function profiles: total lung capacity, residual volume, forced expiratory volume in 0.75 second, forced expiratory volume in 1 second/forced vital capacity, and maximal mid-expira tory flow rate.3 Results were related to dust exposure4 and smoking and have been described in full elsewhere.3. Close to half the men (44.3 percent) had normal lung function profiles and a further 26.5 percent had minor function changes only. Among the remainder, restrictive and obstructive function profiles occurred with com parable frequency (12.8 percent and 12.2 percent re spectively). Roth were associated with radiologic fea tures of asbestosis; both occurred infrequently in the absence of the smoking habit (Table 1.) These findings suggest an association between the smoking habit and the development of an aslu-stos-related fibrosis in so far as this is reflected in a restrictive function profile. In I'r.iir. the Department of Epidemiology and Health. McGill University, Montreal, ami I Limersite tie Sherbrooke, Sher brooke, Qneliec, Canada. Supported Ijy the MI1C (Canada) and the Institute of Oc cupational and I '.nvirounn-nlal Health of the Duel we Asbes tos Mining Association G. l-'onrnier-MiLssey Inltl an MitG Fellowship: M. It. Hccklake is an Associate of the MliC `For all measurements, prevalence % has been age-standard ized to the total working population as of Ortober 31st, 1966. This was to allow for the smaller number of men for whom function profiles were analyzed. `Expressed in million partirles per cubic foot vearsj fBased on a total sample of 1,015 men*, ** JBased 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 Becklake MR, Foumier-Massey G, Rossiter CE, et al: lung function in chrysotile asliestns mine and mill workers of Quebec. Arch Environ Health 24:401, 1972 2 McDonald JC. Becklake MR. Cibl.s CW, et al: The health of chrysotile asbestos mine and mill workers of Qneliec. Areli Environ Health 28:61, 1974 3 Foumier-Massey G. Becklake MR: Pulmonary function profiles in Quebec asbestos workers. Bull l'liysin-pathologie Ih-sp 11 429. 1)175 4 Gibbs GW, ],,u bailee M; Dust exposure ill the chrysotile aslx'stus mines and mills of Qiu-In-c. Areli Kn\ iron Health 21: 18)1. 1)172 CHEST, 69: 2, FEBRUARY, 1976 SUPPLEMENT 18TN ASPEN CONFERENCE 303 DTH 000042433