bronchial reactivity in aluminum potroom

Lung function and bronchial reactivity in aluminum potroom workers. 1989;15:296- 301. Lung function and bronchial reactivity were measured in 38 aluminum potroom workers with no airway symptoms and in 20 healthy referents (office workers). All of the participants were non smokers. The magnitude of exposure to airborne dust (alumina) and fluor ides was determined. The alu minum potroom workers had obstructive lung function impairment with a significant decrease in expira tory flow and an increase in residual volume. Diffusing capacity was found to be lower than in the refer ents. No bronchial hyperreactivity was found in the aluminum potroom workers. The exposure to inhaled alumina and particulate and gaseous fluorides in the plant was low, 15-20070 of the Swedish exposure limits. The finding of only modest lung function alterations with no bronchial hyperreactivity in the alu minum potroom workers is not consistent with the results of other authors. This discrepancy can proba bly be explained by the fact that the exposure to inhaled contaminants in the investigated aluminum plant was low.

lung function of aluminum potroom workers.We also wanted to determine whether these work ers have an increased bron chial reactivit y and , if alterations in lung function or bronchial reactivity were found, to what extent these chan ges are related to the magnitude of exposure to airborne alumina and particulate and gaseous fluo ride s.

S ubj ects
Th irty-eight male aluminum plant wo rkers [mean age 39 (range 21-63) years] working in a potroom with da ily exposure to airborne alumina and fluo ride s a nd 20 male office workers (the ref erents) from the same plant [mean age 48 (range 24-65) years] participated in th e study.The su bjects of the exposed gro up had been wo rking in the aluminum plant for an ave rag e of 13.6 (SEM 1.4, range 1-32) years.None of the subjects in the referen ce group had been expo sed to a irborn e contaminants in th e aluminum plant with the exception of three, who , mor e th an five yea rs pr ior to the present investigatio n, had had low exposure in the potroom (maintenance work) for less than two years.None of the subjects in the two groups had been smokers in th e two years prior to the time of the tr ial.In the reference group eight were ex-smokers [7.4 (SEM 2.0) pack-years], and in the expo sed gro up 14 were exsmokers [11.4 (SEM 2.5) pack-years].Th ere was no significant differen ce in earlier smoking habits.All of the participants were reque sted to complete a question naire and an oral interview with regard to present and former air way and allergic symptoms .Cough , phle gm , dysp-nea, rhinoconjunctivitis, atopic dermatitis, urticaria, and symptoms of asthma were inquired about.With the exception of minimal pleural thickening in one subject and pleural plaque in one, all the participants had a normal chest radiograph.All the subjects gave their informed consent to participate in the study, which had the approval of the Ethics Committee of the University of Urnea,

Lung function measurements
All the participating subjects completed the lung function study and the bronchial provocation tests.The lung function tests were performed in the upright sitting position.The tests were repeated two or more times unless otherwise stated, and the best value was chosen .The lung volumes have been corrected to body temperature and pressure saturated with water vapor (BTPS).The signals from a dry rolling seal spirometer, the nitrogen meter with a pneumotachograph, and a body box of the hybrid type were transformed and transmitted to a computer through a microprocessor controlled by an analogue-digital converter.The computer was a scientific type microcomputer (Hewlett-Packard 98 I6) and the applied software was written in the laboratory .
Vital capacity was obtained from a slow expiration from the total lung capacity (TLC) to residual volume.The total lung capacity and residual volume were measured in a body box according to the method described by DuBois et al (14).The predicted normal values for the static lung volumes were taken from Grimby & Soderholm (15).
The dynamic lung volumes and flows were obtained from a maximally forced expiration six or more seconds in duration after a maximal inspiration.The starting point of the expiration was obtained by backward extrapolation to the zero volume change of the steepest part of the volume-time curve.The FEV 1.0 ' the maximal expiratory flow at 50 0,70 of the expired forced vital capacity (MEF so), and the mean transit time from the start to 6.3 s of the expiration were calculated from the curve (out of three) with the highest sum of the forced vital capacity and the FEV 1.0'The predicted normal values, according to age and body length, were those of Berglund et al (16) for FEV 1.0 and those of Hedenstierna et al (17) for MEF so .The predicted normal values for the mean transit time were taken from Macfie et al (18).The FEV 1 0 was expressed as the FEV % [(100 x FEVl.o)/slow•VC], a~d the predicted normal values of Morris et al (19) were used.
The single breath nitrogen washout maneuver was performed by measuring the nitrogen concentration during a slow expiration from the total lung capacity to the residual volume after a full in spiration (from residual volume to total lung capacity) of oxygen.The closing point and the slope of the alveolar plateau (phase III) were determined from the curve of the nitrogen concentration as a function of volume on the com-puter screen by the use of an interactive technique with cursors.The closing volume was defined as the volume between the closing point and the end of the expiration.Closing capacity (CC) was calculated as the sum of the residual volume and closing volume.The closing capacity was also expressed as a percentage of the total lung capacity (CC/TLC %).Phase 111 was the slope of the alveolar plateau as the change in the nitrogen concentration per liter of expired air .It was defined as the average slope from the onset of the alveolar plateau to the closing point.For these calculations the curve with the greatest volume (which should be close to the vital capacity) was chosen.The reference values were taken from Hedenstrorn et al (20).
The single breath pulmonary diffusion capacity for carbon monoxide (TLcos B ) (in miIlimoles per minute• kilopascals) was the mean of two measurements.If the second value differed more than 10 % from the first, an additional measurement was performed.The method followed the recommendations of the European Coal and Steel Working Party (21) as it is applied in the automatic test system by Mijnhardt (Diffusimat 2000).The reference equation was taken from Salorinne (22).

Bronchial challenge test
Bronchial provocation comprised inhalations of methacholine in increasing concentrations, each increment of the dose representing a fourfold increase in the concentration.After the diluent was inhaled , the methacholine challenge began at a concentration of 0.5 mg/mI.The inhaled solution was nebulized in a DeVilbiss nebulizer (no 40) (DeVilbiss Company, Somerset, Pennsylvania, United States) and was inhaled by tidal breathing during 1 min .The breathing pattern of 2 s of inspiration and 2 s of expiration was guided by a metronome.Peak expiratory flow (PEF) was measured 3 min after the inhalation maneuver was started, and the best value of three measurements was chosen.The provocation was stopped when the peak expiratory flow decreased by ~20 % of the baseline values, ie, the values obtained before inhalation of the diluent or after the inhalation of the highest concentration (32 mg/ml).The PC 20PEF and PCIOPEF, ie, the concentration of methacholine that yields a peak expiratory flow decrease of 20 and 10 % from the baseline values, respectively, were calculated.

Exposure 10 airborne alumina and fluorides
Exposure was assessed for different work tasks from measurements of samples obtained in the breathing zone of the workers during 8 h of work.The mean exposure of eight workers with the same type of work was calculated.Air was collected with a personal filter sampler (cassette holder for a 37-mm filter, Scantee Laboratory Equipment, PartiIle, Sweden) attached to the worker's collar and was sucked through a O.8-llm filter (Millipore AB, Vastra Frolunda, Sweden) at a rat e of 1.85-1.95IImin.The filter sampler also contained a cellulose-acetate filter impregnated with sodium-formiate for the adsorption and determination of gaseous fluorides (23,24).The capacity of the suction pump (Casella AFC 123, Nordiska Miljoin strument, Stockholm, Sweden) was controlled with a calibrated rotameter before , during, and after the sampling periods .The concentration of total airborne dust was determined by the weighing of the filter.
Th e exposure of inha led dust and fluo rides was estimated for each wor ker according to the type of work performed and the time of exposure.The workers were divided into low, medium , and high exposure gro ups according to the magnitude of the expos ure.This estimation of extrapolated exposure was made with regard to tota l (lifetime) exposure and exposure during the year preceding the study, ie, during 1987.The magnitude of exposure wa s also estimated and categorized into the cat egories low and high when respirators had been in use.
During certa in work tasks the exposure can be much higher tha n the measured background levels.Under such circum stances, measurements were ta ken dur ing 15 min of work (" worst case estimate" ).

Statistical methods
The results have been presented as the mean values and the standard error of the mean (SEM) .A P-value o f < 0.05 was considered significant.For the statistical anal yses, the analysis of variance (ANOY A) and twotailed Student's t-test for independent observations were used .The statistical analyses of the lung fun ction da ta were performed with the use o f the percentages of the predicted values.The statistical evaluation of bronchial rea ctivity was perform ed by mean s of th e Mann-Whitney U-test.

Results
On e subject in each gro up had mild asthm a and pollen rhinitis.Ho wever, all of the other parti cipant s were free from present and former allergic sympto ms of the skin and airways.None of the participating subjects had considerable symptoms from the airways, such as coughing, phlegm , or dyspnea (ie, none had symptoms of chronic bronchitis).

Lung j unction
The lung function of the referent s was norm al in comparison with the predicted norm al values o f all the parameters measur ed except TL cosll , which was reduced (P = 0.022) (table I).
In the potro om workers, significant decreases in FEY1.0 (P=0.004),MEF so (P=0.006), and TL c OSIl (P = 0.044) and a significant increase in residual volume (P = 0.049) were observed when these subjects were compared with the refer ents (table I).With regar d to all the other lung fun ction values, there were no significant differences between the two gro ups even if a tendency towards increases in CC/ T LC lIlo (P = 0.059) and mean transit time (P = 0.094) were observed in the exposed gro up.
There was no significant di fferen ce (ANO YA) in the lung fun ction o f the workers with high and those with low exposure (figure I).Th is finding was valid for both tot al dust and fluorides, total life expos ure, and the exposu re during the preceding year (ie, 1987).In addition, when the use of respirators was ta ken into consideration, the lung function did not differ between the high and low expos ure gro ups.

Bronchial reactivity
Th e PCzoPEF could be determ ined for onl y one o f the referents and three of the expose d workers.All of  the other subjects tolerated the highest methacholine concentration (32 mg/ml) without a decrease in peak expiratory flow of ~20 070.The PCIOPEF could be determined for eight of the referents and 13 of the exposed subjects.The mean was 10.0 (SEM 2.7) mg/ml for the exposed group and 15.6 (SEM 3.4) mg/ml for the reference group.There was no significant difference between the two groups (P = 0.45).
tionship at this low range of exposure.Another possible explanation is that our methods of measuring exposure did not adequately discriminate between different doses of inhaled contaminants in this low range of exposure.The modest reduction in the FEY 1.0 was accompanied by an increase in residual volume, and these results suggest that the obstruction was mainly peripheral.This hypothesis is also supported by the

Exposure to inhaled alumina and fluorides
The exposure data have been summarized in table 2.
The "worst case estimates" showed mean values for gaseous fluorides of up to 3.13 mg/rrr' during work with gas scirt exchanges.

Discussion
Table 2. Classification of the aluminum potroom workers (N =38) according to the magnitude of their exposure throughout their lifetime and during the preceding year (ie, 1987).In Sweden there is only one aluminum plant (GA Metall) located in Sundsvall in the middle of the country.Most of the plant workers use respirators to protect themselves against airborne contaminants.The concentration of airborne alumina and fluorides in the factory was only 15-20 % of the respective Swedish exposure limit, which is 10 mg/rn' for alumina and 2 mg/mm' for fluorides.The exposure measurements were performed during 8 h of ordinary work in the plant.During certain work tasks, such as gas scirt exchanging, however, the exposure can be higher, and this "worst case estimate," measured during 15 min, can exceed the Swedish exposure limits for gaseous fluorides (highest level was 3.13 mg/rn') for short periods of time.
The objective of the present study was to investigate all of the nonsmoking potroom workers in the GA Metall aluminum plant and to recruit the referents from the unexposed employees in the same factory.The number of nonsmoking employees not working in the potrooms was limited, and therefore it was not possible to match the groups with regard to age (mean age being nine years higher for the reference group).Thus the lung functions of the groups were compared from calculations of all the lung function variables as the percentage of predicted values, the confounding effect of age thereby being eliminated.
There was a highly significant decrease in the FEY 1.0 of the exposed group when these workers were compared with the referents, and obstructive lung function impairment was therefore indicated for the aluminum potroom workers.The group mean value of the FEY 1.0 was however modestly decreased (93 % of the predicted value), and this finding congrued with the fact that all of the subjects in the exposed group were free from airway symptoms.The lack of correlation between lung function and the magnitude of exposure indicates that there is no dose-response rela-finding of an impaired TLcOS B and the tendency towards an increase in CC/TLC % in the exposed group.These small changes in lung function Were not associated with symptoms of asthma in the present study.
The findings of obstructive lung function impairment without asthmatic symptoms in the aluminum potroom workers is in agreement with the results of some earlier studies (2).However, other investigations have found an increased prevalence of bronchial asthma in aluminum potroom workers (5,6).We found no alteration in the slope of the alveolar nitrogen plateau, which is the best discriminant for the early detection of the type of peripheral airway obstruction observed in tobacco smokers (25).The pathophysiological mechanism behind this change in the nitrogen concentration per liter of expired air is not clear, but a development of centrilobular emphysema might be of importance.Hence the minor airway obstruction found in the aluminum potroom workers of the present study does not seem to reflect the early changes of emphysema, but rather seems to resemble the changes observed in chronic obstructive pulmonary disease without emphysema.The finding of asthma in aluminum workers in other studies supports this hypothesis.
In the present study we found no difference in bronchial reactivity between the exposed workers and the referents.Thus the bronchial obstruction was neither accompanied by asthmatic symptoms nor by bronchial hyperreactivity.This finding is not in accordance with earlier findings of bronchial hyperreactivity against histamine (1) and methacholine (3) among aluminum potroom workers.This difference may, at least partly, be explained by the decision to select only nonatopic subjects for work at the aluminum plant in the present study.In the investigation by de Vries et al (1), the concentration of airborne fluorides was however approximately 13 times higher than the concentration in the present study.This difference in exposure seems to be the most probable explanation for the discrepancy between the occurrence of bronchial hyperreactivity in the aluminum potroom workers of the present study and the findings of de Vries et al (1).

Figure 1 .
Figure 1.Relationships between the exposure to alumina and fluorides (total, ie, lifetime, exposure and exposure during the year preceding the study, ie, 1987) and the lung function of 38 aluminum potroom workers.The means and standard errors of the means are presented.(1 = low, 2 = medium, and 3 = high exposure; RV =residual volume, FEV 1 .0 =forced expiratory volume in 1 s; TLcoS B = single breath pulmonary diffusion capacity for carbon monoxide)

Table 1 .
Lung function of 38 alumi num potroom wo rkers (ex posed subj ect s) and 20 healthy ref erent s.The mean s, as the pe rcentage of th e predicted values , and the 95 % confidence int ervals (95 % CI) for th e means are giv en.If the 95 % CI doe s not include 100 %, the difference between the resp ective mean value and the predicted normal valu e is statistically sign if icant.(FEV1.O =forced expiratory volume in 1 s, MEFso=maximal ex pi ratory flow at 50 % of the expired forced vital capacity, TL coSB = si ngle breath pulmon ary diffusion capaci t y for carb on monoxide, NS = not sig nif icant)