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Reprinted from British Journal of Industrial Medicine 1984;41:328-333 Copyright 1984 British Journal of Industrial Medicine All rights of reproduction of this reprint are reserved in all countries of the world Epidemiological study of the lung function of worker, at a factory manufacturing polyvinylchloride M H LLOYD, S GAULD, L COPLAND AND C A SOUTAR British Medical Association, Tavistock Square, London WC1H 9JR VC5723 British Journal of Industrial Medicine 1984;41:328-333 Epidemiological study of the lung function of workers at a factory manufacturing polyvinylchloride M H LLOYD. S GAULD, L COPLAND AND C A SOUTAR From the Institute of Occupational Medicine, Edinburgh EH8 9SU, UK abstract A preliminary epidemiological study has been carried out to investigate a report that some men working in a factory manufacturing polyvinylchloride (PVC) had abnormally low values of the single breath diffusing capacity for carbon monoxide (Tlco). All 265 present and past employees of the PVC factory were studied, together with 219 men from the workforce of a nearby foundry. Each man's TlCO was measured and a smoking history' and detailed occupa tional history obtained. The distribution of standardised TlCO results from all persons examined was symmetrical and did not indicate an unexpectedly high proportion of men with clinically important impairment of TlCO. The results of a case-control study showed that, having allowed for age, height, weight, and smoking habit. TlCO was associated with a history of working in the PVC factory before 1975 (when levels of vinylchloride monomers (VCM) were much higher than subsequently), and slightly associated with working in jobs where exposure to VCM was likely to have been highest. The men with low TlCO also tended to have smoked more heavily than controls. The relative importance of occupational factors and smoking in relation io low Tlco i* not clear, but the results give some support to the hypothesis that work in the PVC factory before 1975 entailed exposure to a substance that caused impairment of lung function in a smail number of men. The management and occupational physician of a factory making polyvinylchloride (PVC) had become concerned over an apparent excess in their workforce of men with impairment of the single breath transfer factor for carbon monoxide (Ti_C0). The present study was planned to determine whether there was such an excess of men with low values of Tlco in the workforce, and to make a preliminary assessment of whether low- Tl^O might be related to occupational factors. The factory had been in operation since 1969 and produced PVC powder from vtnvlchlonde monomer gas(VCM). All men who had worked at the factory, whether or not they were currently employed there, were invited to participate in the study. A sample of men working in a nearby foundry were also invited to participate: they had been exposed to the same environmental conditions outside the workplace and were included in order to augment the number of men in the study who had not been exposed to poss ible hazards in the PVC factory. Received 28 February 1983 Accepted 9 Mey 19B3 Methods SELECTION OF SURVEY POPULATION All 177 men currently employed at the PVC tact were invited to take part and attempts were made to trace and invite all the 263 former employees At the foundry, the study was confined to 285 men selected randomly from the 1085 current male em ployees. The number of men at the foundry aged under 25 was limited to 15 to take account of a disproportionately large number of young men in the foundry population compared with the PVC workers and to provide a group of similar size to the 13 PVC workers of this age. Apart from this, selec tion did not take account of age. MEDICAL SURVEY The medical survey team visited the factories and recorded a full occupational history since leaving school for each man. Trained personnel using a questionnaire which was a modified version of the Medical Research Council questionnaire ot respiratory symptoms' recorded details of each man s smoking history. Additional questions were related to age of starting smoking and the numoer of 328 VC5724 Epidemiological study of the lung Junction of workers at a factory manufacturing polyvinylchloride 329 cigarettes smoked during a man's maximum smok ing period. Measurements of single breath gas transfer factor for carbon monoxide were carried out on all men using the breathholding method-' based on the mod ified Krogh technique (transfer test B;PK Morgan Ltd, Chatham. Kent). The mean of two measure ments was used in the subsequent analysis. All PVC factory employees had forced expiratory volume in one second (FEV,) and forced vital capacity (FVC) measured using an electronic dry rolling seal spirometer (Ohio 800). The best of three technically satisfactory measurements was used for the analysis. Approval was not obtained for FEV, and FVC measurements in the foundry workers. METHODS OF ANALYSIS Analysis of data from the total survey population The data were studied initially by summary descrip tive statistics and by multiple linear regression analysis of lung function taking into account age, height, weight, and smoking habit. Men were assigned to one of three smoking categories: lifelong non-smoker, current smoker, and ex-smoker. The two smoking groups included smokers of pipes, cigars, and hand-rolled cigarettes but the majority smoked manufactured cigarettes. In the regression model used for both TlCO and FEV, different intercepts and age slopes were allowed for the three smoking groups, non-smokers, current smokers, and ex-smokers. This means that the estimated effects of age were not constrained to be the same necessarily in the three smoking habit groups. The relation between a man s observed and pre dicted lung function values was expressed as a stan dardised residual (SR). This is defined by the equa tion: __ (observed va)ue_value predieied from fined equation) SR -- (estimated standard deviation of the prediction) The distribution of FEV, and Tlco SR values of the whole population was examined. Case-control study For each lung function variable, those men with the largest negative SR value were chosen as cases. Two groups of controls were selected randomly, firstly, from those men whose SRs were clustered around zero ("average" controls) and. secondly, from those with largest positive SRs ("healthiest" controls). Two groups were chosen because men with average values may have included some whose lung function had been slightly affected by noxious influences, whereas those with very high values were least likely to have been affected by noxious influences but Table I Classification of all jobs at PVC factory into wj broad occupational groups. Brood occupational group Jobs included m t'oup 1 All men working m reactors i anc 1* Drver room B operators* 3 Dryer room Lead, A anc 4 B operators 4 Warehousemen, maintenance star: laboratory staff, and dmen: 5 General staff who visit plant, suer ^ shift supervisors and foremen 6 Management and otnee sic:' *Mcn mon likely to have been exposed id high concentration' .v VCM in the past. tMen engaged in the bagging of PVC and probably exposed higher concentrations Of dust than other workers m the dryer buildings. tMen potentially exposed to all taw materials and products might include men who were highly resistant to these influences. Cases were initially compared with the rest of the survey population in order to identify any systematic differences in age. smoking habit, and employment status. Then the occupational and smoking histones of cases and controls were examined and compared. Smoking histones were classified as they were tor the total population, but additional information about the number of cigarettes smoked and the ace of starting smoking was analysed in the case-contrc! study. Broad occupational categones were defined for the PVC factory (table 1) and for the founcrv and the total number of years spent by cases and controls in each occupational category was calcu lated. Additional information was available for P\ C employees in relation to exposure to emulsion polymer (which has a smaller panicle size than sus pension polymer and which was manufactured at the factory between 1971 and 1974) and employment in the factory before 1975 when levels of VCM were much higher than the currently permitted levels From the full occupational history the number ot years spent in potentially "noxious" industries i such as coal, steel, chemicals, and a miscellaneous group of industries in which exposure to noxious com pounds might have occurred) was recorded. In the analysis Fisher's exact test, the chi-squared test for 2 x 2 contingency tables, and the chisquared test for linear trend were used where appropriate. Results A total of 488 men was seen, consisting of 165 cur rent PVC factory employees (93% of those who were asked to participate). 102 PVC former em ployees (39% of those invited), and 221 foundry employees (78% of those invited). Four men (two PVC and two foundry) were excluded from the VC5725 Epidemiological study of the lung function of workers at a factory manufacturing polyvinylchloride 331 Table 3 Features ofFEV, cases, controls, and total survey population. Mean (and standard deviations) of age. height, weight. TICO, FEV: and FVC Table 5 Smoking habits ofTjjCQ cases, controls, and total survey population. Number of men in each smoking category with percentages in parentheses No of men TLCO groups Total Cases 1301 Controls Controls population tavengei (heaithttsn (264) (301 (30) Aae (jr): Mean (SD) Height (cm): Mean (SD) Weight (kg): Mean (SD) FEV, (1): Mean (SD) FVC (1): Mean (SD) TlCO (ml/min mm Ha)Mean (SD) *3-3 (1**03 176-0 (7*4) 82 2 (13-3) 2-7 (0-7) 4' 1 (09) 29-1* (6-8)* 41-3 (12-5) 174-5 (6-6) 78-4 (101) 3-9 (07) 51 (08) 32-3 (6-0) 42-1 (120) 175-9 (8*0) 804 (11-5) 4-5 (08) 5-9 (09) 31 3 (6-5) 42-2 (11-8) 174-3 (7-1) 80*4 (12-3) 3-7 (09) 4*9 (1-0) 305* (6*1)T `Value bated on 29 observations. tValue based on 262 observations. had worked in more than one type of job and in more than one broad occupational category during their employment with the companies. More cases than controls had worked in jobs in category 1 (on or near the reactors) at the PVC factory: 11 of 31 cases (35%) had worked in this category compared with 10 of 62 controls (16%) and this disproportion is significant at the 7% level (table 4). No suggestive differences were seen m the pattern of employment of FEV, cases and controls. More cases than controls had worked at the PVC Caws Controls (average) Controls (healthiest) Total survey population Sonsmokft 3 (9-7) 4(12-9) 7 (22-6) 109(22-5) Current smoker 20(64-5) 13 (48-4) 15 (48-4) 234 (48-4) Ei*smoker 8 (25-8) 12 (38-71 9(29-0) 141 (29-li Total 31 31 31 4g4 factory before 1 January 1975. when levels of vinylchloride were much higher than at present. Seven teen of the 19 Tico cases who had worked at the PVC factory had been employed before 19*5 whereas only five of the 15 healthiest controls and 11 of the 13 average controls had been. The differ ence between cases and healthiest controls was significant (p < 0-002), and the increase in the proportion of men with pre-1975 employment m the PVC factory for the three groups over healthiest controls, average controls, and cases was also statis tically significant (p < 0-001). Analysis of the dura tion of employment of men within different age groups showed that pre-1975 working was seen m both younger and older men. A similar analysis o; FEV, cases and controls and foundry Tlco cases failed to show any significant differences in relation to working before 1975. These findings suggest that some factor or factors associated with working at the PVC factory before 1975 had caused impairment oi T^co in some men. There was no difference in the numbers of TlCO or FEV, cases and controls who had been exposed Table 4 Numbers of men who had spent some time in each occupational group. IMean time Iyears) spent in each occupational group) So of Occupations! groups / 2 2 45 6 7s V 30 n j 13 Cases. PVC workers FounOrymen 19 12 11 \1 4 4 -l j1 (2 (0-6) (7-PI (9*0) ?9.V) (7 0) 4 < (5*6) 7 * f 1 4) 1 (7-3) (3-0) (12 3) (4-0) (3-2) ("H`4) iH" Average controls: PVC workers Foundrymen I? 1* 4 151 IT l07i (6M IPU) (12 3) 3 5 1 9 t i 1^ ^ (4-6) (16 11 (304) (94) (7-4 1 110-6i 12 f HcaJthieti controls' PVC worker* Foundrymen 15 16 6 11 1 ?7 3) fi-ji 1 13*0) (1*0) U0-H) n 5 (13*4) (4*5) w1 (J-Ol (05 38 112 7) 112-5) 6 M - Note: Occupational groups 1-6 reter to P\ C faciorv (see table I and "M 3 iobs at the foundrv--mat is " work on or near the rurnautf' % aand work and shot-blasnng. 9 grinding and welding. 10 general joe*. 11 painting and dipping; 12 easting work. 13 femme VC5726 Epidemiological study of the lung function of workers at a factory manufacturing polyvinylchloride 3.'.' that both were important. The men with the lowest Ti_CO values selected as cases were not all necessar ily suffering from lung disease but among them were 15 men whose Tlco was less than 70^ of the value predicted by published normal values, a level which probably indicates the presence of disease. In eight of the 19 cases who had worked at the PVC factory the low Tlco was an isolated abnormality, a pattern unlikely to be the result of damage from smoking and which is usually associated with interstitial lung disease or disturbance of pulmonary perfusion. Reports of both animal and clinical studies give further support to the suggestion that exposure to VCM might have been an important causative fac tor. Animal studies have shown that exposure to high levels of VCM leads to pulmonary fibrosis, the changes being most severe in the animals which had been exposed for the longest time* There have been isolated case repons of individuals with interstitial lung disease who had been employed in the man ufacture of PVC and who had, therefore, been exposed to VCM.*10 Hunter et al described six such workers, three of whom had died from liver disease related to VCM exposure*; none of the six had respiratory symptoms, three had abnormal chest x rav films, and one an abnormal Tlco, but the lung histology from all six men showed a similar picture with the presence of an inflammatory interstitial infiltrate. Diligent attempts were made to contact all men who had worked at the PVC factory but response was low (39^). If the men not examined had included either an excess or deficiency of men with impaired gas transfer factor compared with the population examined then the analysis of the dis tribution of values among the population seen would be unrepresentative to that extent. We conclude that this preliminary study has shown no evidence that current working conditions in either factory have caused impairment of lung function but it does give some support to the hypothesis that work in the PVC factory before 1975 emailed exposure to a substance that caused impairment of lung function in a small number of men. Further work including clinical studies of affected men would be necessary to characterise this impairment and to explore more fully the relations with occupational and other factors. This study was carried out with the full cooperation of the management and workforce of Vinatex Limited to whom we are grateful for financial sup port. We thank the management and employees of the foundry for their generous cooperation in the study and the medical officers at Vinatex and British Steel for their help. We also thank Dr A Seaton and Dr M Jacobson for their advice. Further details of the results of the work are recorded in institute of Occupational Medicine report TM/82,4. References 1 Medral Research Council working parry on research im.' chronic bronchitis. Report. London: Medical Research Coun cil. 1976. ; Meade F. Saunders MJ. Hyett F. Reynolds JA. Pearl V O'tsJE- Automatic measurement of lung tunchon Lanea 1965:ii:573-5. ' Coles JE. Lung junction. Oxford Blackwell Scieninc Publica tions. 1979:369-k5 ` Soutar CA. Copland LH. Thomley PE. ft at bnac-niiM'ioc... study of respiratory disease in workers exposed io poiyumlehlondc dust. Thom 19X0:35:694-53. ' Mastrangelo G. Manno M. Marcer G. etal Polyvinvl chloride pneumoconiosis: epidemiological study of exposed worker? JOM 1979:21.54(1-:. * Darke CS. Vinyl ehlondc and the production of PV C Proceedinfs of the Raval Society of Medicine 19*6, ' Lange CE. Julie S. Siein G. Veltman G Die xogenanme Vinvlchlond*Krankheit eine bemfvbedingie Swemsklero-e 1 Imernanonai Arcnn Arbettzmeditin 1974.32, l-.'Z * Hunter AM. Wagner JC. Johnston N. Seaion A Lung nhro-is in polyvinylchloride workers Thorax 1981.36 "11-1 - Prodan L, Suciu 1. Pisiaru V'. Ilea . Pasuu L. Expenmenral chronic poisomna with vmvl chloride Imonochloroethanei Ann .Vy Acad Sa 197J-.M6 159-63 " Amaud A. Pommier de Sami P. Gartoe L. Payan H. Charpin J Polyvinyl chloride pneumoconiosis. Thorax 1976,33:19-25 VC5727