Document NG40Rmnk33dK2oqr8yJRqrv8V

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 m all countries of the world Epidemiological study of the lung function of workei. at a factory manufacturing polyvinylchloride M H LLOYD, S GAULD, L COPLAND AND C A SOUTAR British Medical Association, Tavistock Square, London WC1H 9JR 007695 CHA 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 95U, UK abstract A preliminary epidemiological study has been earned 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 Tt_CO results from all persons examined was symmetrical and did not indicate an unexpectedly high proportion of men with clinically important impairment of Ti_CO. 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 to low Tlco is 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 small 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 (Tlco). 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 Tlco might be related to occupational factors. The factory had been in operation since 1969 and produced PVC powder from vinylchloride monomer gas (VCM). AH 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 Miv 1983 Methods selection of survey population All 177 men currently employed at the PVC factory were invited to take part and attempts were made to trace and invite all the 263 former employees Ar 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 leasing school for each man. Trained personnel using a questionnaire which was a modified version of the Medical Research Council questionnaire of respiratory symptoms' recorded details of each man's smoking history. Additional questions were related to age of starting smoking and the number of 328 CMA 007696 --Epidemiological study of the lung function of workers at a factory manufacturing polyvinylchloride ,'2v cigarettes smoked during a man s maximum smok ing penod. 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: (ofcMivcd value--value predicted from Aned equation) (ensnared naodwd deviation of the predicooai 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 1 Classification of all jobs at PVC factors into >i.t broad occupational groups. Broad occupational group Jobs included m group 1 All men working in reactors [ and 3' 2 Drver room 0 operators7 3 Dryer room Lead. A ana A B operators 4 Warehousemen, maintenance star: laboratory staff, and dmers: 5 General staff who visit plant, suen shift supervisor? and foremen 6 Management and since tun *Mcn most likely to hive been exposed to High concentrations ot VCM in the put. Men engaged in the bagging of PVC end probably exposed to higher concentrations of dust than other workers m the dner buildings. tMen potcnnaUy exposed to ail raw 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 histories were classified as they were (or the total population, but additional information about the number of cigarettes smoked and the age of starting smoking was analysed in the case-control study. Broad occupational categories were defined for the PVC factory (table 1) and for the foundry, 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 particle 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 of yean spent in potentially "noxious" industries < 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 Fishet'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 007A97 CMft 330 -3-2-1 O' 2 3 SR valut Fig 1 Number of men by ranges ofT^CO standardised residuals. Tlco analysis because of incomplete data, and to the final analysis was based on 484 men. As FEV, and FVC measurements were not obtained from three PVC factory workers and all 221 foundrymen this analysis was based on 264 men. The distributions of standardised residual values of TlCO and FEV, for the total survey population after allowing for age. height, weight, and smoking habit were fairly symmetrical and conformed approximately to Normal distributions (figs 1 and 2), although for FEV, there were slightly more extreme negative values than extreme positive val ues. SELECTION OF CASES AND CONTROLS A threshold SR value for Tlco of -1-5 supplied 31 men. a number that was considered large enough to form a study group. A control group of 31 men was selected randomly from those men with SR values between -0-25 and +075 inclusive (TlCO average controls). A second control group of 31 "extra heal thy" men was selected randomly from those with SR values in excess of +075 (TlCO healthiest con- Llo\d. Could. Copland. Snttt1 Table 2 Features ofT[^CO cases, controls, and total sun ^ population. Mean land standard deviations t of age. hetgnt weight and Tj^co So of men TLCO groups Tutdi Caansts Controls Controls pupuia: (aavnerage) tahenalthiest) t-tfi-i - A(y), Mean (SO) Hettfit (cm): Mean (SD) Weight (kg): Mean (SDI Ti CO (mlrain mm Hg): Mean (SDl 4| 8 (10-21 176-1 (7-1) 82-7 (13-3) 22 2 (4-II 42.1 (12 3) 174 0 (6-6) 84-9 (18-5) 318 (2 9i < n 3i l73 v (5-6) 79 2 (9-5) 37-3 (4 3) 4' * f li *1 1" * (7 0) so-: (12 01 30- ? (5 trols). Similarly, 30 men with an FEV, SR value of less than -11 were selected as FEV, cases and two groups of controls (FEV, average controls and FEV, healthiest controls) were chosen from those men with SR value between -0-25 and -*-0-75 and in excess of +075 respectively. CLINICAL FEATURES OF CASES. CONTROLS. AND THE TOTAL POPULATION The general features of TlCO and FEV, cases, con trols. and the total population are shown in tables 2 and 3. The mean age of the T^CO case and control groups were similar. a Observed T^CO and FEV, values of the casfl were also expressed as a percentage of values pre dieted on the basis of Cotes' regression equation Fifteen of the 31 Tlco cases had Tlco values below 70% of their predicted values: four were below 60%. Twelve of these 15 men were PNC workers and three were foundrymen. Nineteen of the 31 cases were from the PVC factory and four ot these had evidence of airflow obstruction (FEN1, < 80% and FEV/FVC < 70%); examination of forced expiratory flow-volume loops suggested that a further seven might have mild airflow obstruction. In the remaining eight the low Tlco appeared to be an isolated abnormality. Of the 30 FEV, cases. 13 had observed FEN values below 80% of their predicted values and 111 of these men had FEV/FVC ratios below 70% sug gesting airflow obstruction. Seven of the FEV, cases also qualified for inclusion as Tlco cases. Fig 2 Number of men by ranges of FEV, standardised residuals. OCCUPATIONAL HISTORIES Analysis of employment status showed that 19 of the TlCO cases worked or had worked at the PN C factory and 12 were foundrymen. but this difference could easily have arisen by chance. Most workers CMA 00769 Epidemiological study of the lung function of workers at a factory manufacturing polyvinylchloride 331 Table 3 Features of-fEV, cases, controls, and total survey population. Mean (and standard deviations) of age, height, weight. T[_CO, FEV and FVC Table 5 Smoking habits ofTf_CO cases, controls, ana total survey population. Number of men in each smoking category with percentages in parentheses No of men Cases 130) TiCO groups Total survey Controls Controls population toverageI /healthiest) (264) (30) (30) Ate ty) Mean (SO) Height (cm): Mean (SD) Weight (kg): Mean (SD) FEV, (1): Mean (SD) FVC (1): Mean (SD) TiCO (ml/min mm Hg): Mean (SD) 43-3 (110) 176-0 (7-4) 82-2 (13-3) 2-7 (0-7) 41 (09) 29-1* (68)* 41-3 < 12-5) 174-5 (6-6) 78-4 (101) 3-9 (07) 51 (08) 32-3 (60) 42 1 (120) 175-9 (8-0) 804 (11-5) 4-5 (08) 5-9 (09) 31-3 (65) 42-2 (tl-8) 174-3 (7-1) 804 (12 3) 3-7 (09) 4-9 (10) 3057 (61)7 `Value baaed on 29 observations, tValue baaed on 262 obaervanona. had worked in more than one type of job and in more than one broad occupational category dunng 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 in the pattern of employment of FEV, cases and controls. More cases than controls had worked at the PVC Cases Controls (average) Controls (healthiest) Total survey population Sonsmoker 3 (9-7) 4(12-9) 7(22-6) 109(22-3) Current smoker 20(64-3) 15(48-4) 13 (48-4) 234 (48-4) Es-smoker Totn 8 (25-8) 12(38-') 9 (29-0) 141 (29-11 31 31 31 484 factory before 1 January 1975. when levels of vinylchloride were much higher than at present. Seven teen of the 19 Ti_CO cases who had worked at the PVC factory had been employed before 1975 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 in 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 seefi-in both younger and older men. A similar analysis of 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 atthe PVC factory before 1975 had caused impairment of Tlco in some men. There was no difference in the numbers of T[_co or FEV, cases and controls who had been exposed Table 4 Numbers ofmen who had spent some lime in each occupational group. (Mean time (years) spent in each occupational group) No of Occupational group* / 2 j 4 3 6 7 8 9 to 11 12 13 Cases. PVC workers Fowadrymen Avenae controls: PVC workers Foundry-men 19 12 13 18 11 u 4 - (2-7) (0-6) (7*6) (9-0) (9-71 4 (7-01 * (6-7* l (6*1 < <6-U> 1 < 12 3) 1 <701 4 (7-3) (23-OS 5 <5-61 5 72 (12-3) (40) ,,(3-2i 1 (1 4) y1 m-4i [ [-0* 35 I9l j 1 (4-6) (161) (304) (9*41 (74) (U)-fS* <: 5- Hrahhieil controls: PVC workers Fouadrymcn 15 16 6 13-0* 11 n-o> 1 (10-K) <7-3> A (3-31 1 (17) 53 (13-4) (4-51 21 (4-0) (0-5) 38 U2-7| (12-51 -- - 6 HIM -- Note: Occupational groups 1-6 refer to PVC factory (see table 11 and 7-13 jobs at the foundry--that is. 7 work on or near the furnaces ' sand work and shoi-blaiting: 4 (nndinf and welding: 10 general jobs. 11 painting and dipping: 12 casting work. 13 fettling 007699 CMP 332 Lloyd. Could, Copland, Soui^l Fig 3 Number of cigarettes smoked a day at weekends among current smoking T^co cases and healthiest controls. Fig 4 la) Age as start of cigarette smoking among T[_CO cases and healthiest controls who were current smokers, (b) Age at start of cigarette smoking among T^CO cases and average controls who were current smokers. to emulsion polymer at the PVC factory. No evidence was obtained that the observed dif ference between cases and controls could be explained on the basis of previous employment in industries other than the PVC factory or foundry. SMOKING HABITS OF CASES AND CONTROLS Whereas the procedure for selection of cases and controls had taken account of whether a man smoked, it was found that the Tj_CO cases had tended to smoke more than controls. A slightly higher proportion of Tlco cases (65%) were cur rent cigarette smokers than either group of controls (on average 48%) (table 5). and more of these cases smoked 25 cigarettes or more at the weekend than the healthiest controls (fig 3). Weekday smoking fol lowed a similar'but statistically insignificant pattern. The Tlco cases tended to have started smoking at an earlier age than controls (fig 4). Whereas exposure to PVC dust has been shown to be related to a mild reduction of lung function chest x ray abnormalities,4 5 less is known about the pulmonary effects of exposure to VCM. There have been some case reports of men exposed to VCM who had impairment of lung function, particular!) Tlco,*7 and changes in lung histology have been reported.*' The present study was designed as a preliminary examination of whether an undue number of men at this PVC factory had impaired Tlco, and whether such impairment was likely to be related to their occupation. We have found no evidence of a sub stantial excess of men with impairment of the Tlco. although low T^CO values were found in a few men. as might be expected in any large population of workers. After allowing for other factors, however, those men with the lowest Tlco tended to have worked more often than would be expected at the PVC factory before 1975. a date before which con centrations of VCM were known to have been much higher than subsequently; these men also tended slighdy to have worked in the jobs where the highest concentrations of VCM were found. This evidence gives some support to the hypothesis that work in the PVC factory entailed exposure to one or more substances that caused impairment of lung function in a small number of men. The most likely substance is VCM. on which suspicion has previously been cast by case repons of vinylchtoride workers with impairment of gas trans fer factor, but in which proof of association has ba^ lacking.*7 It is also possible that exposure to res^A able PVC dust may have contributed to the low pp transfer factors although there was little positive evidence for this in our study. PVC dust has been shown in other studies to be associated with impair ment of other aspects of lung function (though not the gas transfer factor) and slight chest .t ray abnor malities.4 * There was little evidence to support, as an alterna tive hypothesis, the suggestion that the workforce recruited in the early years of production included an excess of men with poor respiratory health at the time of entry to the factory. The FEV,. a more sensi tive indication of the common types of chronic respiratory illness, was not found to be particularly adversely affected in men working in the factory before 1975. The selection of cases took into account w hether a man smoked, but even after allowing for this, the cases with low TlCO tended to have smoked slightly more than the controls, and notably the age at which a man started to smoke appeared to be related to low Tlco. The relative contributions towards impairment of Tlco of smoking and of occupational factors arc not clear from this study, but it is possible CMA 007700 Epidemiological study of the lung Junction of workers at a factory manufacturing polyvinylchloride 3 -that both were important. The men with the lowest TLCO values selected as cases were not all necessar ily suffering from lung disease but among them were 15 men whose Tj^co 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 T[_co 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*,0 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 ray films, and one an abnormal T^co, 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 entailed 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 thn, 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 Vinaiex 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 Medical Research Council working party on research into chronic bronchitis. Repen. London Medical Research Coun cil. 1976. ; Meade F. Saunders MJ, Hyett F. Reynolds JA. Pearl N. Coie JE. Automatic measurement of lung (unction. Lenm I96j:ir573-J. ' Cotes JE. Lung function. Oxford: Blackwell Scientific Publica tions, 1979:369-#?. * Soular CA. Copland LH. Thomley PE, rt at. Epidemiological study of respiratory disease in workers exposed lo polywnvlchlortde dust. Thorax 1980:36:644-32. 1 Mastrangelo C. Manno M. Marctr C. ft al Polyvwvl chloride pneumoconiosis: epidemiological srudv of exposed uorke'j JOM 1979;Jl: <40-:. * Darke CS. Vinyl chloride and the production of PVC Proceed ings of the Royal Society of Medicine 1976. ' Lange CE. Julie S. Stem G. Veltman G Die sogenannte Vinylchlond-Krankheit eine berufsbedingte Systemsklercv>e ' International Archie ArbeiKmedinn 1974,32: * Hunter AM. Wagner JC. Johnston N. Setton A Lung fibrosis in polyvinylchloride workers. Thorax 1981.36 711-: ' Prodan L. Suciu 1. Pislani V. flea E. Pasou L Experimental chronic poisoning with vtnvl chloride (monochloroethane i Ann SY Acad Sci 1975:246:139-63 Amaud A. Pommier dc Santf P. Garbe L. Payan H. Charpm J Polyvinyl chlondc pneumocxxnosu Thorax 1978.33:19-25 CMA 007701