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Chronic Respiratory Disease among Workers in a Pulp Mill* Ten-year Follow-up Study nneli Poukkula, u.o; Esko Huhti, M.D.; and Maria Miikariiinen, M.D. 10-year follow-up study was carried out on 659 men aged 18 to 64 years when first surveyed by questionnaire and simple spirometry in 1967, to determine the effect of smoking habits on respiratory symptoms and ventilatory function. Symptoms tended to increase during the follow-up period, and were most marked among the men who continued to smoke. The remission rates of respiratory symptoms were high in au the smoking groups, however, and cough and phlegm actually diminished during the ten years in the men who stopped smoking after the first survey. The follow-up survey in 1977 showed a prevalence of 6 to 8 percent for severe airways obstruction in the ex-smokers and smokers, but only 2 percent in the life-long non-smokers. The average decrease in one second forced expiratory volume (FEVt) was 44 mllyear in the total series, 37 ml/year in the life-long nonsmokers and 49 milyear in the continuous smokers (P < 0.001). The men who had stopped smoking before the first survey resembled the nonsmokers, whereas those who had stopped during the follow-up period resembled the continuous smokers in respect to the decrease in FEV1. survey was carried out in 1966-67 among the men who worked at a pulp mill in Oulu, northern Finland, to determine the prevalence of respiratory symptoms and chronic respiratory disease. t The results revealed the importance of smoking in the etiology of respiratory symptoms and deterioration of ventilation. The aim of the present follow-up survey in the same population in 1976-77 was to assess changes in the prevalence of respiratory symptoms and their association with smoking habits, and the consistency of the respiratory symptoms themselves. n attempt was also made to determine the relationship between ventilatory changes and smoking habits. For simplicity, the first survey is referred to here as having been carried out in 1967 and the follow-up survey in 1977. POPULTION ND METHODS detailed account of the population, locality and methods has been published.' Only the main features are outlined here. The surveys were carried out in the town of OuIu, with a population of about 90,000 and situated by the sea in northern Finland, almost exactly on latitude 65 N. The annual mean temperature in Oulu is 2.4 C and the annual rainfall averages 514 mm. From the Department of Medicine, University Central Hospital, and the Health Center of OuIu Osakeyhti0, Oulu, Finland. Reprint requests: Dr. Poukkula, Department of Medicine, University Central Hospital, SF-90220 Oulu, Finland The First Survey The men who worked at a pulp mill were examined for respiratory symptoms and ventilatory function in 1967. part from wood pulp, the mill also produces chlorine and various by-products of wood processing. The men eligible for the survey numbered 953, and of these, 905 (95 percent) presented for examination. fter the exclusion of 89 men with pulmonary tuberculosis or "other respiratory disease" as defined later, the group to be followed-up consisted of 816 men. standard questionnaire on respiratory symptoms approved by the Medical Research Council Committee on the etiology of Chronic Bronchitis and translated into Finnish" was filled in for each man. lthough the questionnaire classifies breathlessness into five grades, the two most severe grades are combined here to form a new grade 4, which corresponds to the division used in the more recent forms of the questionnaire. Height and weight were measured and simple spirometry- was performed, enabling the determination of forced vital capacity ( FVC ) and onesecond forced expiratory volume (FEV1)' and thus the ratio of FEVt/FVC in percent (FEV 1 %). The highest values for FVC and FEV1 (in BTPS) from five forced exhalations were taken for use here. The men were classified by smoking habits into: 1) nonsmokers, 2) ex-smokers, and 3) smokers. When subdividing the smokers according to the amount smoked daily, one cigarette was assumed to contain 1 g of tobacco. bout 10 percent of the men smoked a pipe or cigars, but these were not classified separately. The diagnoses in the survey were based on the following criteria: Chronic bronchitis: Production of phlegm on most days for at least three months in the year unless attributable to a CHRONIC RESPIRTORY DISESE IN PULP MILL WORKERS 285

local or specific lung disease. Phlegm production may have occurred during the whole day or only part (usually in the morning). The diagnosis includes both simple and more complicated forms of chronic bronchitis. 4 Chronic airways obstruction (CD): FEV1% less than 60. sthma: The diagnosis was accepted if based upon hospital examinations. Pulmonary tuberculosis: diagnosis made on the usual clinical, radiologic and bacteriologic criteria. lmost all cases consisted of inactive processes of long standing, with large residual changes in the lungs. Other respiratonj diseases: Other respiratory diseases and anomalies, insofar as they were assumed to be of clinical significance, but excluding emphysema, Hence the patients with emphysema were included in the follow-up series, but were not treated as a separate group. The Second Survey The follow-up survey carried out ten years after the first used essentially the same methods and criteria, and the questionnaires were filled in by the same assistant. The population examined is detailed in Table 1. For various reasons, mostly due to some severe extrapulmonary disease, spirometry could be performed only on 636 men. To analyze the effect of smoking habits, the series was classified into the following groups: Group 1: men who were nonsmokers at both surveys; group 2: men who had stopped smoking by the first survey and had not re-started; group 3: men who were smokers at the first survey, but had stopped by the second; group 4: men who smoked at both surveys. Thirty men could not be included in the above groups, and being a small group, they were excluded from most analyses. Both surveys were conducted in winter, from November to February. Four men are included who were inadvertently misclassified in 1967. In cases where only percentages are shown, the absolute frequencies of events can be obtained from the authors upon request. Standard statistical methods were used, eg, the X 2 test and t test \V hen testing the significance of the differences in frequencies or group means. If no P value is shown, the term "significant" refers to the 5 percent level. Smoking Habits RESULTS The number and percentage of the non-smokers did not change much during the follow-up period (Table 2), while the number of smokers had decreased and the number of ex-smokers had correspondingly increased. The amount smoked daily had decreased among the smokers. These changes Table I-Sur1'ey Population Examined in 1H67 816 Dead by 1977 54 live in ]977 762 Could not be contucted 99 Refused follow-up examination 4 Re-examined in ]B77 659 % of those alive 86 Table Z-Smoking Habit, in The 658 Men Re-examined in 1977 Survey Year 1967 1977 No. % No. % Non-smokers 133 20 127 19 Ex-smokers 141 21 237 36 Smokers 384 58 294 45 1-14 g zday 133 20 122 19 15-24 g/day 200 30 136 21 25- g/day 51 8 36 5 Smoking habits were not known in one man occurred in a similar manner in all the age groups except for the youngest, aged 18 to 24 years in 1967 (only 48 men), for whom the proportion of smokers was 69 percent in both surveys. Respiratory Symptoms and Chronic Respiratory Disease Symptoms tended to increase during the followup period, among the continuous smokers in particular, the largest increases occurring in severe breathlessness (Table 3). Cough and phlegm diminished among the men who had stopped smoking in the interim, however. The trends in symptoms were essentially similar in the various age groups (data not shown). There was no distinct difference in the prevalence of asthma between the various smoking groups in Table 3-Pre1'alence (%) oj Re,piratory Symptom, by Smoking Habib in 1967 and 1977 1 2 3 4 Non-sm Ex-sm Ex-sm Smoker 1977 1977 1977 1977 No. of men 126 118 116 268 Cough all day - "Tinter 1967 2 3 14 15 1977 3 7 3 22 Phlegm all day - winter 1967 5 7 18 19 1977 7 11 6 20 \Vheezing most days 1967 1 3 3 4 1977 2 --1 7 17 Breathlessness grade 3-4 1967 2 4 6 5 1977 8 17 13 18 Mean age (years) in 1967 37 42 40 37 286 POUKKUL, HUHll, MKRINEN

Table 4--Pre1'alenee (%) of sthma, Chronic Bronchitis and Chronic irways Obstruction (CO) by Smoking Habits in 1967 and 1977 1 234 Non-sm Ex-sm Ex-sm Smoker 1977 1977 1977 ]977 No. 126 No. 117 No. 1]5 No. 268 sthma 1967 1 3 1 1977 2 6 3 3 No. 126 No. 118 No. 116 No. 268 Chronic bronchitis 1967 6 8 34 30 1977 12 15 1 1 37 No. 119 No. 108 No. 106 No. 251 CO 1967 1 1 3 2 1977 2 6 8 8 either survey, but its prevalence had slightly increased from 1967 to 1977 (Table 4). The prevalence of chronic bronchitis was similar among the non-smokers and ex-smokers in both years, and increased between the surveys in all groups except group 3, in which it diminished. The prevalence of CO was higher in 1977 than in 1967 in groups 2, 3 and 4, but there was no notable increase among the non-smokers. Many subjects lost their symptoms during the follow-up period, the remission rates being high in all the smoking groups (Table 5). Remission of CO was uncommon. Ventilatory Function The rate of the decrease in FEV1 varied between the smoking groups over the intervening ten years. Table 5-Recovery from Respiratory Syntptonls or Disease (as % of Those with it in 1967) in the 10-Year Follow-up Period by SIltoking Habits 1 2 3 4 Non-sm Ex-sm EX-8m Smoker 1977 1977 ]977 1977 Cough all day-winter 100 50 88 55 Phlegm all day-winter 100 75 86 56 Wheezing most days 100 67 67 40 Breathlessness grade 3-4 50 40 71 38 Chronic bronchitis 75 67 78 34 Chronic airways obstruction 100 The average decrease in FEV1 in the total series was 44 ml/year (SD 33 ml/year), the extremes being an increase of 85 ml/year and a decrease of 195 ml/year. The non-smokers (group 1) showed the smallest average decrease, 37 ml/year, whereas the continuous smokers (group 4) had the most rapid rate, 49 ml/year (Table 6). The rate of decrease was similar in groups 1 and 2, and also in groups 3 and 4. There were differences in the rate of change between the various age groups, but no general trend with age. To determine whether the decrease in FEVl was associated with phlegm production, we divided each of the four smoking groups into two subgroups, the men without phlegm production and those with phlegm production (Table 7). In groups 1, 2 and 4, the men with phlegm tended to show a more rapid decline in FEV1 than those without phlegm, but in no case was the difference significant. mong the men without phlegm, those who stopped smoking during the follow-up period and the continuous smokers showed a significantly more rapid decline in FEV1 than the non-smokers. Chlorine Exposure No significant differences in the prevalence of respiratory symptoms were found between the men who worked in the chlorine plant and those from the other sections of the factory, and the rate of decrease in FEV1 was similar in both categories, allowing for smoking habits. Table 6-Decrease in FEY) (mllyear) by ge and Smoking Habits Smoking group ge in 1967 (years) ~, ]8-24 25-34 35-44 45-54 55-64 Total Group 1 No. of men 5 52 41 16 9 123 Decrease in FEV. 55 32 45 38 19 37 SD 29 28 33 29 37 31 Group 2 No. of men 3 24 35 38 ]3 113 Decrease in FEV. 57 48 35 39 30 39 SD 26 41 38 36 20 36 P NS NS NS NS NS NS Group 3 No. of men 5 37 36 24 9 ]11 Decrease in FEV. 43 45 55 42 49 48 SD 22 36 32 27 42 33 P NS NS NS NS <0.05 <0.0] Group 4 No. of men 27 90 87 41 13 258 Decrease in FEV. 37 47 53 54 42 49 SD 33 24 35 35 27 31 P NS <0.001 NS NS NS <0.001 P values refer to comparison with the non-smokers (group I) in the respective age group. CHRONIC RESPIRTORY DISESE IN PULP MILL WORKERS 287

Table 7-D~rea.e Production and Smokin«Habit. in FEJ'l (mllyear) by Phlegm No phlegm in Phlegm in 1967 Smoking group 1967 or 1977 and/or 1977 Group 1 No. of men 104 19 Decrease in FEV) 36 44 SD 32 30 Group 2 No. of men 86 27 Decrease in FEV) 36 48 SD 32 46 P NS NS Group 3 No. of men 67 44 Decrease in FEV) 48 48 SD 31 36 P <0.02 NS Group -I No. of men 135 123 Decrease in FEV) 46 52 SD 31 31 P <0.02 NS P values refer to comparison with the non-smokers (group 1) in each column. There were no significant differences between the men with and without phlegm within the smoking groups. DISCUSSION The results confirm that smoking increases respiratory symptoms and impairs ventilation, whereas stopping smoking may abolish these effects, at least in part. They do not necessarily apply to the general population, however, as the men studied were a selected group of factory workers who were able to work when first examined. Similarly, those who died during the intervening period were not considered. Even so, we know (unpublished data) that only two out of the 54 men who died (4 percent) were non-smokers in 1967. The men who died had more obstruction and a lower FEVt in 1967 than those who remained alive. This implies that the effect of smoking on the occurrence of respiratory symptoms and the decline of ventilatory function may in fact be stronger than is suggested by the results. The ex-smokers resembled the non-smokers in the prevalence of cough and phlegm, but inclined towards the smokers in the prevalence of breathlessness as noted by Sharp et a1. 5 Respiratory symptoms proved remarkably unstable in all the smoking groups, and the remission rates were high even among the smokers (Table 5). This suggests that more objective measures should be utilized when investigating changes in the lungs over a longer period, and slight changes in the prevalence of symptoms, although perhaps "statistically significant," may not be important at all. Similar high 288 POUKKUL, HUHll, MKRINEN remission rates have been noted in previous studies. s-8 More decisive for a patient's outcome than the symptoms is the development of airways obstruction, resulting in a decrease in ventilatory capacity. The incidence of CO was similar in the exsmokers and smokers, and clearly higher than in the non-smokers, which resulted in higher prevalences in groups 2 to 4 than in group 1 in 1977 (Table 4). CO was a more stable finding than the respiratory symptoms; only one man (a nonsmoker) recovered from his CO during the ten years. Hence, although the prevalence of phlegm production (bronchitis) decreases after smoking has been stopped, the same is not true of airways obstruction, which is a more ominous sign than even copious sputum. FEV t decreased faster in the smokers than in the non-smokers (Table 6), as noted in previous longitudinal studies.p:" In those ex-smokers who had stopped smoking before the first survey ( group 2 ), the decrease in FEV1 was similar to that of the non-smokers, which suggests that the decline in ventilatory function may slow down when smoking is discontinued. similar conclusion was reached by Comstock et ai,12 and also by Fletcher et al'" on the basis of their eight-year follow-up study of 792 middle-aged men. We found no significant differences in the decline of FEV t between the men with and without phlegm in any of the groups 1 to 4, and in groups 3 and 4 in particular the differences were slight or nonexistent (Table 7). This stresses further the relative independence of airways obstruction and sputum production, which has also been pointed out by Fletcher et al. t O It is obvious that a severe obstruction may develop in men not producing any phlegm or, on the other hand, phlegm production may not greatly influence the development of airways obstruction. The exposure to low concentrations of chlorine did not seem to affect ventilation in this industrial population, and a largely similar result was reached by Ferris et al t 3 in their ten-year follow-up study. They suggested, however, that Cl2 might have a slightly adverse effect on pulmonary function and advised further studies in larger populations. The results obtained point in the same direction as those obtained in a previous follow-up survey on another population at Harjavalta, southern Finland," but with one notable difference. t Harjavalta, the men who had stopped smoking before the first survey (group 2) still had a faster decline in FEV1 than the life-long non-smokers. The population in Oulu consisted of men able to work when

first studied, which implies that they were relatively healthy, perhaps with mainly reversible changes in the lungs and bronchi. The men at Harjavalta were an un selected population and included some with severe chronic bronchitis or emphysema. This suggests that stopping smoking is relatively more advantageous in those subjects with only slight changes in their bronchi than in the far advanced cases of bronchial obstruction, CKNOWLEDGMENTS: This study was supported by grants from the Finnish nti-tuberculosis ssociation, the Paulo Foundation, and the Yrjo Iahnsson Foundation. REFERENCES 1 Huhti E, Byhanen P, Vuopala U, Takkunen J. Chronic respiratory disease among pulp mill workers in an arctic area in Northern Finland. cta Med Scand 1970; 187: 433-44 2 Huhti E. Prevalence of respiratory symptoms, chronic bronchitis and pulmonary emphysema in a Finnish rural population. cta Tuberc Pneumol Scand 1965; Suppl No. 61 3 McKerrow CB, McDermott M, Gilson IC. spirometer for measuring the forced expiratory volume with a simple calibrating device. Lancet 1960; 1:149-51 4 Medical Research Councils Committee on the etiology of Chronic Bronchitis. Definition and classification of chronic bronchitis for clinical and epidemiological purposes. Lancet 1965; 1:775-9 5 Sharp JT, PaulO, McKean H, Best WR. longitudinal study of bronchitic symptoms and spirometry in a middle-aged, male, industrial population. m Rev Respir Dis 1973; 108:1066-77 6 Ferris BG Jr, Chen H, Puleo S, Murphy RLH Jr. Chronic nonspecific respiratory disease in Berlin, New Hampshire, 1967 to 1973. further follow-up study. m Rev Respir Dis 1976; 113:475-85 7 Ferris BG Jr, Higgins ITT, Higgins MW, Peters JM. Chronic nonspecific respiratory disease in Berlin, New Hampshire, 1961 to 1967. follow-up study. m Rev Respir Di~ 1973; 107: 110-22 8 Woolf CR, Zamel N. The respiratory effects of regular cigarette smoking in women. five-year prospective study. Chest 1980; 78:707-13 9 Higgins ITT, Gilson JC, Ferris BG Jr, Waters ME, Campbell H, Higgins MW. IV. Chronic respiratory disease in an industrial town: a nine-year follow-up study. Preliminary report. m J Public Health 1968; 58:1667-76 10 Fletcher C, Peto R, Tinker C, Speizer FE. The natural history of chronic bronchitis and emphysema. London: Oxford University Press, 1976 11 Huhti E, Ikkala J. 10-year follow-up study of respiratory symptoms and ventilatory function in a middleaged rural population. Eur J Respir Dis 1980; 61:33-45 12 Comstock GW, Brownlow WJ, Stone RW, Sartwell PEe Cigarette smoking and changes in respiratory findings. rch Environ Health 1970; 21 :50-7 13 Ferris BG Jr, Puleo S, Chen HY. Mortality and morbidity in a pulp and a paper mill in the United States: a ten-year follow-up. Br J Ind Med 1979; 36: 127-34 CHRONIC RESPIRTORY DISESE IN PULP MILL WORKERS 289