Document e5RKqOw3d1qbyQ3JKoOvXjpwy

BIO-MEDICAL.RESEARCH DOCUMENT DESCRIPTION FORM 63 68 69 && 76 Duplicate.In all cards:--> year as-1961- File number [Right justify onlvl Author(s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space .sapta-P, ca Ps Pirrn ' L J-f j p ... 4 7rfAr\./ 'Tfi'sZA'PVr, p*r /PAA7IJS IZ.PrP. 77 78 I^ i Sub-Index Code 51 62 11 12 13 Title of Report; end with space-hyphen-hyphen-space. Follow with Index Terms separated from each other with comma-space. Avoid other punctuation; do not abbreviate. r~~----------------------- ----- T---------------- --: ^^7P r7K>/^LAAYcP^ S~OPJ' AA / f //s tA/'Pji(Ctn&r$ tPAPA 3 yA 77 PS / C/^ U/ ss/SpgjnP, frzfzrtrp j)/S'/?'Sc <?- /)rr7~- .. Cc/z^cfy ' 21 22 23 24 Source (Journal, Vol., Number, Pages, Date ) 12___________________________________________________ ____ T/rsf/HC 3 s', .fff? 1 62 ~3l 32 Brief Summary 12 10 SUMMARY: 61 62 61 62 63 64 EPIDEMIOLOGICAL STUDY OF RESPIRATORY DISEASE IN WORKERS EXPOSED TO POLYVINYLCHLORIDE DUST </j>4 R&S 114433 BY C A SOUTAR, L H COPLAND, P E THORNLEY, J F HURLEY, J OTTERY, W G F ADAMS, and B BENNETT Reprintedfrom Thorax September 1980 Vol 35 No 9 p 644 COPYRIGHT 19*0 Thorax L RIGHTO OF REPRODUCTION OR THIS REPRINT ARE RESERVED IN ALL COUNTRIES OP THE WORLD BRITISH MEDICAL ASSOCIATION TAVISTOCK SQUARE LONDON WC1H 9JR Thorax. 1980, 35, 644-652 R&S 114434 Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust C A SOUTAR, L H COPLAND, P E THORNLEY, J F HURLEY, J OTTERY, W G F ADAMS, AND B BENNETT From the Institute of Occupational Medicine, Edinburgh, and Imperial Chemical Industries Limited abstract The respiratory health of workers exposed to polyvinylchloride (PVC) dust has been investigated in 818 men sampled from the work force of a factory manufacturing PVC. In a crosssectional survey, the lung function and prevalences of respiratory symptoms and chest radiographic abnormalities were compared with estimates of individual PVC dust exposures based on detailed occupational histories and current measurements of respirable PVC dust. Complaints of slight exertional dyspnoea were associated with PVC dust exposure, though age and smoking effects were much stronger. The forced expired volume in one second (FEV,) and forced vital capacity (FVC) were inversely related to dust exposure after age, height, and smoking effects had been taken into account. This effect was seen principally in cigarette smokers, and there was suggestive evidence that PVC dust exposure and cigarette smoking interacted in the reduction of FEV, and FVC. Gas transfer factor was not related to dust exposure. The chest radiographs were read according to the ILO U/C classification by three experienced readers. One reader recorded a low prevalence of small rounded opacities, and these were not related to age or dust exposure. Another reader recorded a higher prevalence of small rounded opacities category 0/1 or more, and these were related to age but not to dust exposure. The third reader recorded the highest prevalence of small rounded opacities ; (though none greater than category 1/1), and these were independently related both to age and to j PVC dust exposure, indicating an effect of PVC dust on the appearances of the chest radiograph. I JThese appearances were so slight that only the higher sensitivity of this reader in the interpretation of profusion of small rounded opacities on the ILO U/C scale enabled detection of this effect of PVC dust. In conclusion, exposure to PVC dust is associated with some deterioration of lung function, slight abnormalities of the chest radiograph, and complaints of slight dyspnoea. The mean decline in FEVi associated with the average dust exposure experienced in the study was small, though some of the men with higher dust exposures may have suffered clinically important loss of lung function as a result of their occupation. The dust produced during the the manufacture of polyvinylchloride (PVC) includes a large pro portion by number of small particles of respirable size.1 * Administration of PVC dust to animals has been reported to cause inflammatory changes of the bronchioles and alveoli, including a proli feration of histiocytes and granulomatous lesions,1 * and PVC formulations have been found to have cytotoxic effects in vitro.-1 These effects were caused in part by the plasticisers, stabilisers, and other additives in the PVC, and there is some evidence that the in vitro toxicity of PVC Address for reprint requests: DrCASoutar, Institute of Occupational Medicine, Roxburgh Place, Edinburgh EH8 9SU. dust is related to the presence of surfactant in the formulation.8 8 Case reports1011 have described pathological changes in the lungs of workers exposed to PVC dust. In several surveys of PVC workers increase of respiratory symptoms, abnormalities of lung function and of the chest radiograph have been described, although these findings have been dif ficult to evaluate, principally because of lack of satisfactory control groups, failure to take ade quate account of the effects of age, cigarette smoking, or general atmospheric pollution, and lack of darity in descriptions of radiographic readings.212*18 Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust 645 Methods STUDY POPULATION The sample.to be studied was selected in January 1979 from 1501 currently employed men, 339 pensioners (men who received a pension from the manufacturer, most of whom were over 60 years of age) who had retired since 1 January 1967, and 468 men leaving for other reasons since that date. Men were selected for study according to broad categories of cumulative dust exposure derived from factory records and preliminary estimates of dustiness based on inspection of the plant and measurements of size ranges of typical PVC dusts. The sampling scheme aimed to include all men with heavier dust exposures, and lesser proportions of those with lighter exposures. One hundred and fifty-six men with high or moderate dust exposures did not attend for survey, and were replaced by reserves drawn from moderately exposed groups. Finally 818 men were studied, comprising 663 currently employed men, 98 pensioners, and 57 men who had left for reasons other than retire ment ("leavers")- Single breath gas transfer for carbon monoxide was measured in 332 men sampled proportionally but randomly from each exposure category. ENVIRONMENTAL SURVEY Current personal exposures to respirable PVC dust were measured by occupation in each plant in which PVC was manufactured or processed. Preliminary estimates of dustiness were based on subjective observation by the sampling team and on particle size measurements of typical suspen sion and emulsion PVC dusts, and the major sampling effort was directed towards the appar ently more dusty occupations in the drying, packing, and mixing areas. One hundred and thirty reliable personal samples of respirable PVC dust were obtained from men in 44 different occupations for full shift periods on Sartorius cellulose ester membrane filters (type 11301), diameter 37 mm, pore size 80 jim, inserted into a Casella Simpeds 70 cyclone.10 This device samples a "respirable" fraction of airborne dust in accordance with the Johannesburg Convention,17 including 100% of all particles with an equivalent aerodynamic dia meter of 1 pm, 50% of those of 5 pm, and none greater than 7 jun. medical survey A full occupational history was recorded, and the Medical Research Council Questionnaire of Res piratory Symptoms18 was administered by a trained clerk. Forced expiratory volume in one second (FEVj) and forced vital capacity (FVQ were measured using a modified Gaensler spirometer.19 The best of three measurements was used for the analysis. Single breath transfer factor for carbon mon oxide (Tlco) was measured by the breathhold ing method20 based on the modified Krogh technique (Transfer test B, PK Morgan Ltd., Chatham, Kent). Effective alveolar volume (Va) was measured by helium dilution in the same single breath, and used in the calculation of Tlco and Kco. The means of two observations were used in the analysis of these measurements. A full-size postero-anterior chest radiograph was taken by a standard technique (95--120 kV). The chest radiographs were read independently using the ILO U/C International Classification of Radiographs of Pneumoconioses11 by three readers highly experienced in this work. The readers had all been shown previously t pro duce readings that correlated with measurements of dust exposure in coalminers and to be highly consistent in their readings when presented with the same films on separate occasions. They did, however, represent a range of interpretation of profusion of small opacities recorded using the ILO U/C scale, and were known to differ corisistently from each other in the prevalences of small rounded opacities they recorded. PVC DUST INDEX Every occupation within the population under study was allotted a PVC dust concentration on the basis of the measured current dust levels. Sixty-six such job/dust categories were derived from the measurements made and from knowl edge of the factory conditions. A "dust index" was derived from the current dust measurements and the occupational history such that the current dust levels in each of a man's occupations in the plastics factory was multiplied by the years he had spent in that occupation, and this figure added to the figures derived from his other occupations in the factory. statistical methods The data were studied initially by cross-tabula tions, graphical methods, and summary descrip tive statistics. Multiple linear regression analyses of the lung function results were carried out, with subsequent examination of residuals. The radiographic and respiratory. symptoms results were studied by maximum likelihood logistic analysis.22 646 C A Soutar et a! Results ENVIRONMENTAL SURVEY Respirable dust levels were highest in the older plants and those making polymer by the emulsion method. The highest mean average respirable dust exposure for any occupation over a shift was 2-88 mg/m3 (SD+1-84). The distribution of calculated dust indices (years X mg/m3) for the 818 men studied in the medical survey is shown in fig 1. MEDICAL SURVEY Features of the population of 818 men are set out in tables 1 and 2. It was noted in preliminary analysis that the number of years worked at the PVC works or work in an outside industry in which noxious materials were used were of trivial importance in explaining the prevalence of symptoms, lung function and radiographic abnormality, after index of dust exposure, age, and smoking habit had been taken into account. Respiratory symptoms Analysis of respiratory symptoms was based on the answers to the questionnaire. Two hundred and fifteen men (26%) admitted to dyspnoea on exertion grade 1 ("shortness of breath when hurrying on level ground or walking up a slight hill*'). Prevalence was approximately three times higher in the smoking groups (32% in cigarette smokers) than in the non-smokers Table 1 Features of 818 men studied, according to currently employed, pensioner, or other leaver status. Dust index is expressed in years x mg/m1, but does .not represent actual dust exposure, since only current dust levels are known Current workers Pensioners Number 663 Mean age (yrs) 44-2 (SD) (10-8) Mean height (cm) 1730 (SD) (6-J) Mean weight (Kg) 77-7 (SD) (10-5 Mean dust index 13-39 (SD) (12-84) Years at the plant 14*34 (SD) (8-48) Mean FEV, (1) 3-54 (SD) (0-83) Mean FVC (1) 4.62 (SD) (0-88) Mean FEV,/FVC 0*76 (SD) (0-08) 98 63*4 (7 1) 170*2 (3-4) 75-6 (108) 14-23 (11-86) 16-63 (8-06) 2-43 (0-73) 3-41 (0-78) 0-70 (0-11) Leavers 37 43-2 (10-2) 171*2 (6-2) 77*4 (133) 4-86 (6-69) 3-46 (5-48) 3-53 (0-72) 4-34 (0-80) 0-78 (0 06) (10%). A strong age effect was also apparent, prevalence approximately doubling for every 13 years of age in this population. A dust effect was indicated (p=0*054) after adjustment for age and smoking, and this effect was clear in current cigarette smokers (p<002, 10 dust index units increased the estimated prevalence by. a factor of about 20%) after allowing for age and life time cigarette consumption. The dust , effect was not demonstrated in the other smoking cate gories, though these differences between smoking categories could have arisen by chance (p<0-5). R&S 114436 Fig 1 Frequency of dust indices. number of men with dust exposure =0. `-I** Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust 647 Table 2 Numbers of men and (mean dust indicesf of 818 men grouped by age and smoking category. Units of dust indices are years x mg/m' - Ags groups {yr) < 35 Non-smokers Cigarette smokers Other smokers Ex-smokers All 50 (4-1) 65 (5-2) 3 (3 0) 37 (6-6) 155(5-2) 35-44 41 (6-7) 97(12-0) 11 (14-7) 48 (12-9) 197(11 3) 45-49 16(8 2) 60(16-4) 12(13-8) 35 (14-5) 123 (14-5) 50-54 16(12-3) 60(16-6) 9 (19-4) 41 (16-5) 126(16-2) 55^59 5(15-4) 55 (18-4) 12(19-1) 31 (16-3) 103 (17-7) 60 + 20(15-2) 41(16-9) 11 (11-7) 42(18-1) 114(16-5) All 148 (8-0) 378 (13-7) 58(15 0) 234(14-2) 818 (12-3) No relationships were demonstrated between height, weight, and smoking habits (the model in dust index and history of chronic cough or table 3), the overall loss of FEV, associated with sputum, asthma or history or acute chest illness. one dust index unit (years X mg/m5) was estimated as 0 0041 litres. This would be equiva Forced expired volume in one second lent to a loss of 53 ml of FEV, for the mean dust Preliminary analysis indicated different rates of index, additional to the estimated losses caused loss of FEV, because of age between the smoking by age and smoking (26 ml per year in non- categories, and different mean levels of FEV, smokers, 39 ml per year for cigarette smokers according to current, pensioner, or leaver employ plus an additional 5-6 ml per year for each ment status. These differences were taken into packet of cigarettes smoked per day throughout account in the regression model, which also took the year). account of height, weight, and lifetime cigarette In currently employed cigarette smokers con consumption. sidered separately (the model in table 4), the loss Within this framework index of dust exposure associated with dust index was estimated as 84 was significantly inversely related to FEV, mis of FEV, for similar exposure, additional to (p<0025) (table 3). Neither the estimated size the loss caused by smoking and age. The mean nor the significance of the regression with dust FEV, loss in this group of men in relation to index was seriously altered when alternative high dust exposure (40 dust index units or more, models of age and smoking were examined. experienced by: only 4-3% of all the men) was More detailed analysis examined whether the-- estimated at 260 ml. effect of dust index varied according to smoking category and job status groups (current workers, Forced vital capacity pensioners, or leavers). Though the observed dif ferences in dust effect in these groups could have arisen by chance (p--0-45) the numbers of men in some of the subgroups are small, and the pattern of positive and negative effects suggested an interaction between dust effect, current employment at the factory, and cigarette smok A similar sequence of analysis to that for FEV, was followed, with qualitatively similar results. There was a negative effect of dust index on FVC (p<01). Further analysis of dust effect in the smoking and job category subgroups again showed a signi ficant adverse dust effect in cigarette smokers ing (table 4). The dust effect was seen principally in currently employed cigarette smokers. After taking into account the effects of age, Table 4 Regression coefficients for dust index against FEV r Expansion of model of regression for FEVt illustrated in table 3. Table 3 Regression of FEV r Different intercepts for employment and smoking categories allowed but not shown Coefficients and significance of concomitant variables changed little from the model described in table 3. NS-- not significant at the 10% level Variable Height (cm) Weight (kg) Age (yr) f non-smokers ) ex*smokers | other smokers ^cigarette smokers Liretime cigarette consumption (1000 packs) Dust index (years x mg/m*) Regression Coefficient 0-0434 --0-0032 --0 0260 --00350 --0-0489 --0-0392 --0-0154 --0 0041 P <0-0031 <0-2 <0-0001 <0-0001 <00001 <0-0001 <0-0001 <0 025 Cigarette smokers Current workers (number) Leavers (number) Pensioner! (number) --0 0065 (312) (p<0-02) --0-0278 (25) (p < 0*08) -*0 0018 (41) NS Other smokers Ex-smokers Son-smokers --0-0023 (47) NS 0 0468 (3) NS --0 0154 (8) NS --0 0024 (185) NS 0-0246 03) - NS , --0-0004 (36) NS --0-0034 ' (119) NS 0-0118 (16) NS 0-0179 (13) NS 648 C A Soutar et a! Table 5 Prevalence of categories of small opacities found by three readers in 818 chest radiographs. Radiographs in which both rounded and irregular opacities were found are also represented here in the rounded and irregular categories Small roundedt opacifies Reader Category Ofl or more 3 IS (2*20%) 15 4(0*49%) 17 50 (6 11%) Category 1/0 or more 2(0*24%) 2(0*24%) 10(1*22%) Small Irregular opacities Category 0JI or more 32 (3 *91%) 53 (6*48%) 29 (3 *55%) Category 1/0 or more 7(0*36%) 45 (5*62%) 8(0 98%) Both rounded and irregular opacities Category 0/J or more 4(0 49%) 0 (0*00%) 4(0 43%) currently working at the factory (p<0-03). The observed differences in dust effect in these groups could easily have arisen by chance, but an inter action between dust effect, current employment, and cigarette smoking was suggested, broadly similar to that for the FEVi. Other measurements of respiratory function The FEVj/FVC ratio, Tlco, Kco, and Va were not significantly related to index of PVC dust exposure, nor was any sizeable effect indicated. Chest radiographs Small rounded opacities The anticipated differ ences between readers in interpretation of small opacities were apparent (table 5). Reader 17 recorded the greatest prevalence of small rounded opacities: 50 radiographs (6* 1 %) with category 0/1 or more, 10 (1-2%) with category 1/0 or more, the latter consisting of six radiographs with category 1/0 and four with category 1/1. Among these 50 radiographs, there was a strong associa tion between classification by reader 17 as cate gory 1/0 or more and classification by either reader 3 or 15 as small rounded opacities cate gory 0/1 or more (chi-square test, p<0 001), confirming that inter-reader differences in inter pretation of small rounded opacities were differ ences of degree, rather than classification of unrelated appearances. The readings for readers 3 and 17 showed clear relationships between prevalence of small rounded opacities and age (p<0 002 and p<0 001 respectively). The observed data are set out in fig 2. For reader 3, after age had been taken into account, there was no relationship with dust exposure (p=0-83). For reader 17 there was a strong dust effect even after age had been taken into account (p< 0-001, 10 dust index units increased the estimated prevalence by a factor of about 35%). Observed data are set out in fig 3. The dust effect varied according to smoking status (p<002), and was not observed among current cigarette smokers although the age effect was marked. The reason for these differences was not apparent. Reader 17 recorded 10 radiographs showing small rounded opacities category 1/0 or greater, and in spite of this small number, a significant relaticnship with both age (p<0 005) and dust Fig 2 Prevalence of small rounded opacities category 0/1 or more found by three readers, related to age group. R&S 114438 .-i &* 37 flo W Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust 649 KEY*READER CODE I "I I 1,5 4.5 7.5 12.0 Dust index (yr x mg/ma) Fig 3 Prevalence of small rounded opacities category 0/1 or morefound by three readers, related to dust index, index (p<0 02) (after adjusting for the other) was found. Reader 15 classified only four radiographs as showing small rounded opacities: these classi fications were unrelated to age or dust exposure. Small irregular opacities Analysis showed a clear relationship between prevalence of small irregular opacities category 0/1 or greater and age for all three readers (fig 4) (p<0 001 for each reader). There was no relationship of prevalence of small irregular opacities with dust index for any of the three readers. For reader 15 the relationship of small irregular opacities with age could in small part be explained by a positive history of chronic cough or sputum (p<003), and by history of chest illness (p<0-03). Reader 17 also found a relationship of small irregular opacities with chronic cough or sputum (p<0C6), but no relationship with history of chest illness. For both readers, the age effect remained extremely strong even when these symptoms were taken into account. Reader 3 found differences between smoking categories. Prevalence of small irregular opacities was lowest in non-smokers (0-7%) and highest among other smokers (12-1%). These were not accounted for by the different age distributions of the smoking groups. There was no dust effect. Neither of the other two readers identified smok ing differences. Relationship of lung function to the presence of small rounded opacities Reader 17 recorded small rounded opacities category 0/1 or greater in 50 radiographs. The lung function of these men was significantly reduced. The FEVj Fig 4 Prevalence of small irregular opacities category 0/i or more founi by three readers, related to age. 650 C A Soutar et al was reduced by a mean of 206 ml (p<002 after age, height, weight, smoking, cigarette consumption, and dust index had been taken into account (the less complex model described in table 3). The FVC was reduced by a mean of 253 ml (p<001), using the same model, and FEVj/FVC ratio analysed on the log scale was not significantly reduced. Tlco and Kco were measured in 21 of these men, and were not found to be significantly reduced. Va was reduced in these 21 men by a mean of 309 ml (p<O05). Relationship of lung function to the presence of small irregular opacities Radiographs of 90 men were thought by one or more readers to show small irregular opacities 0/1 or greater. The lung function of these men was significantly reduced. Their mean FEVi was reduced by 205 ml (p<001) after adjusting for age, height, weight, smoking category, lifetime cigarette consumption, and dust index (the model in table 3). The mean FVC was reduced by 142 ml, using a similar model (p<0-10). The ratio FEVj/FVC was also significantly reduced (p<0-01, by a factor of 0-97). Tlco was measured in 45 of these men, and was reduced by a mean of 1-52 ml/min romHg (p<005). Va and Kco were not significantly reduced. Autoclave workers The effect of a history of work on the-^autoclaves (where exposure to vinylchloride monomer may have occurred in the past) was examined in the respiratory symptoms, lung function, and chest radiographic abnormality models. A history of having been an autoclave worker had no demonstrable adverse influence on symptoms, lung function, or chest radiographic abnormali ties. Thus there was no evidence that apparent PVC dust effects were the result of exposure to vinylchloride monomer during autoclave working. Clinical readings of chest radiographs The chest radiograph of one man showed advanced diffuse pulmonary fibrosis. This man had a chest radiograph taken though he was not in the intended study sample. The relevance of his disease to his work is currently being in vestigated, but has not yet been established. No cases of lung cancer or active tuberculosis were detected in the survey. Discussion This study was planned to compare the lung function, chest radiographic appearances, and prevalence of respiratory symptoms in workers in a factory manufacturing PVC with estimates of personal exposure to respirable- PVC dust. The random sample was selected from men who had previously worked in the factory as well as the current work force, and was weighted to include a relatively high proportion of those who had the highest lifetime exposure to PVC dust. These preliminary estimates of exposure were based on factory records and a preliminary inspection of the plants and typical dusts pro duced. Twenty-five per cent of selected men, thought on this basis to have high or moderate exposures, did not attend for examination. Reserves for these men were included, albeit that these were from medium rather than high dust exposure groups, to ensure that sufficient numbers of men with substantial exposures were studied. It is emphasised that the dust exposure estimates used in the analysis were not based on these preliminary estimates but on a detailed occupational history obtained from each man together with measurements of current personal exposures in the factory. These estimates, though the best available, may nevertheless have been inaccurate to the extent that previous dust ex posures may have been higher than those presently experienced. In view of probable over all changes in dust levels conclusions about quan titative relationships between dust and disease should be drawn, with caution. It was not possible in this study to take account of the health effects of the components of the PVC powder other than the PVC itself, nor of changes in the formulation occurring over the years. The "respirable" fraction of air borne dust measured in this survey is suitable for comparisons with both bronchial and alveolar disease, for dust in this size range deposits substantially either in bronchial or alveolar zones. Furthermore, measured exposure to "res pirable" coal mine dust has been shown to correlate with mucous hypersecretion and loss of FEV, in miners.12< as well as with the radiographic appearances of pneumoconiosis.115 The study demonstrated a relationship between estimates of exposure to PVC dust and dyspnoea, lung function, and chest radiological abnormality. A history of moderate exertional dyspnoea was related to dust exposure, though this relationship was apparent only in cigarette smokers. This effect was additional to the effects of smoking and aging which were, however, the predominant explanatory variables for this symptom. It seems unlikely that the effect of PVC dust on symptoms R&S 114440 > s 652 slight abnormalities of the chest radiograph and complaints of slight dyspnoea. While these results are not unduly alarming, they do indicate that PVC dust exposure should be controlled, and that the men with radiographic abnormalities should be followed clinically to determine future progression or regression of the condition. This study was carried out with the full co operation of the management and workforce of Imperial Chemical Industries Limited to whom we are grateful for financial support. We are grateful to Dr JA Dick, Dr JG Bennett, and Dr DJ Thomas for the epidemiological radiographic readings, and to Dr A Seaton, Dr M Jacobsen, and Mr J Dodgson for much advice and help. 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