Cobalt asthma--a case series from a cobalt plant.

BACKGROUND: Cobalt has been shown to induce mainly asthma, allergic contact dermatitis and hard metal disease. The data on cobalt asthma are mainly based on case reports. AIMS: To characterize all the cases of occupational cobalt asthma encountered in a cobalt plant at the time of diagnosis and 6 months later. We also evaluated the incidence of cobalt asthma in different departments on the basis of data on occupational exposures. METHODS: We identified cases of cobalt asthma confirmed with specific bronchial challenge tests in the Kokkola cobalt plant in Finland where exposure levels have been regularly monitored. RESULTS: Between 1967 and 2003, a total of 22 cases of cobalt asthma were diagnosed in the cobalt plant. On challenge tests, mostly late or dual asthmatic reactions were observed. The incidence of cobalt asthma was the highest in the departments with the highest cobalt exposure levels. All cases of cobalt asthma were encountered in departments where irritant gases were present in the ambient air in addition to cobalt. At the time of the follow-up examination 6 months later, non-specific hyperreactivity had mostly remained at the same level or increased. CONCLUSIONS: The incidence of cobalt asthma correlated with the exposure levels of cobalt in corresponding departments. An irritating effect of gaseous compounds may enhance the risk of cobalt asthma and even the smallest amounts of cobalt may be harmful to susceptible workers. Symptoms of asthma may continue despite the fact that occupational exposure to cobalt has ceased.

Inflammation and functional outcome in diisocyanate-induced asthma after cessation of exposure.

BACKGROUND: The clinical outcome of diisocyanate-induced asthma has been found to be poor despite cessation of exposure. Our aim was to study the outcome of diisocyanate-induced asthma after initiation of inhaled steroid treatment at a mean period of 7 months (range 2-60 months) after cessation of exposure by following up lung function and bronchial inflammation. METHODS: Bronchoscopy was performed on 17 patients 2 days after a positive inhalation challenge test, after which budesonide 1600 mug a day was started. Bronchoscopy, spirometry, and histamine challenge tests were repeated at 6 months and on average 3 years. The results were also compared with those obtained from 15 healthy control subjects. RESULTS: Nonspecific bronchial hyperreactivity diminished significantly (P = 0.006); however, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values decreased, with a median yearly reduction of FEV1 of 79 ml. The count of mast cells in bronchial mucosa decreased (P = 0.012) and that of macrophages increased (P = 0.001). Interleukin-4 level in mucosa was during the first year significantly higher than in controls but its level decreased in the follow-up. Interleukin-6, interleukin-15, and tumour necrosis factor alpha messenger-RNA levels were significantly higher in hyperreactive patients than in nonhyperreactive patients at the end of the follow-up. CONCLUSION: Our results indicate that inflammation may persist in diisocyanate-induced asthma despite inhaled steroid medication. However, TH2-type inflammation diminished. Persistent nonspecific bronchial hyperreactivity was associated with proinflammatory acting cytokines produced mainly by macrophages. Considering the poor prognosis of the disease the findings could be utilized to develop the follow-up and treatment of diisocyanate-induced asthma.

Glutathione S-transferase genotypes and allergic responses to diisocyanate exposure.

Diisocyanates are the most common low molecular weight chemicals to cause occupational asthma. However, only some 5-10% of exposed workers develop asthma, which suggests an underlying genetic susceptibility. Diisocyanates and their metabolites may be conjugated with glutathione by glutathione S-transferases (GSTs). We examined whether polymorphisms in the GSTM1, GSTM3, GSTP1 and GSTT1 genes modify allergic responses to diisocyanate exposure. The study population consisted of 182 diisocyanate exposed workers, 109 diagnosed with diisocyanate-induced asthma and 73 without asthma. Lack of the GSTM1 gene (null genotype) was associated with a 1.89-fold risk of diisocyanate-induced asthma [95% confidence interval (CI) 1.01-3.52]. Moreover, among the asthma patients, the GSTM1 null genotype was associated with lack of diisocyanate-specific immunoglobulin (Ig)E antibodies [odds ratio (OR) 0.18, 95% CI 0.05-0.61] and with late reaction in the specific bronchial provocation test (OR 2.82, 95% CI 1.15-6.88). Similarly, GSTM3 AA genotype was related to late reaction in the specific bronchial provocation test (OR 3.75, 95% CI 1.26-11.2). The GSTP1 Val/Val genotype, on the other hand, was related to high total IgE levels (OR 5.46, 95% CI 1.15-26.0). The most remarkable effect was seen for the combination of GSTM1 null and the GSTM3 AA genotype which was strongly associated with lack of diisocyanate-specific IgE antibodies (OR 0.09, 95% CI 0.01-0.73) and with late reaction in the bronchial provocation test (OR 11.0, 95% CI 2.19-55.3). The results suggest, for the first time, that the polymorphic GSTs, especially the mu class GSTs, play an important role in inception of ill effects related to occupational exposure to diisocyanates.

Increased prevalence of HLA-Aw19 and of the phenogroup Aw19,B18 in advanced silicosis.

The frequencies of HLA antigens in 27 patients with silicosis were compared with those of referents matched for exposure to silica dust, age, and sex, and having no roentgenographic signs of silicosis. A group of 900 blood donors served as an additional reference group. The prevalence of HLA-Aw19 was higher in the silicosis patients (29.6 percent) than in the silica-exposed referents (3.7 percent; p = 0.02). In turn, the frequency of Aw19 in the unexposed population consisting of blood donors (19.6 percent) was higher than that of silica-exposed referents (p = 0.04). Accepting that the prevalences of HLA antigens in the blood donors fairly well describe those of the silica-exposed population, the highest risk of developing advanced fibrosis was associated with the phenotypic combination Aw19,B18 (observed-expected ratio = 17.05; p less than 0.01). The results suggest that HLA-Aw19 and the haplotype Aw19,B18 are, at least in Finnish population, associated with a progression into advanced silicotic fibrosis.

Increased activity of serum angiotensin-converting enzyme in progressive silicosis.

The serum activity of angiotensin-converting enzyme (ACE, EC 3.4.15.1) in 135 male silicosis patients was analyzed. Twenty-eight of the patients had referents matched for silica dust exposure and age but without roentgenographic signs of silicosis. A reference group not exposed to silica dust comprised 34 lumberjacks. The serum mean activity of ACE was higher in silicosis patients (46.6 +/- 12.1 units/L) than in the referents exposed to silica (38.5 +/- 8.1 units/L) or in the lumberjacks (36.6 +/- 9.7 units/L). There was an association between the serum ACE level and the roentgenographic severity of fibrosis. A retrospective side-by-side assessment of roentgenographic progression was made in 49 silicosis patients. The ACE was higher in the 18 patients with progression (50.5 +/- 16.4 units/L) than in those with no progression (41.5 +/- 9.5 units/L). According to the multivariate regression analysis, progression of fibrosis explained the elevation of ACE better than profusion. The results confirm that the serum ACE activity is elevated in silicosis and suggest that the elevation is associated with progression of the disease.

Progression of asbestosis predicts lung cancer.

STUDY OBJECTIVES: To explore whether the progression of asbestosis correlates with the risk of lung cancer among patients with asbestosis. DESIGN: A group of 85 asbestosis patients (78 men and 7 women) were radiographically followed up between 1979 and 1987. Two or three posteroanterior radiographs taken from each patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according to the International Labour Office 1980 classification and were used to divide the patients into progressors and nonprogressors. Follow-up for cancer was done automatically through the files of the Finnish Cancer Registry from the time of determination of the progression status to December 31, 1994. Predictors of lung cancer risk were studied with a logistic regression model, and the standardized incidence ratio (SIR) was calculated for lung cancer. RESULTS: Of the 24 male patients with progressive small opacity profusion, 11 (46%) developed lung cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer cases occurred among smokers or ex-smokers. None of the seven female patients showed progressive small opacity profusion. One of them developed lung cancer. In the logistic regression model including all 85 asbestosis patients, radiographic progression of small opacity profusion (p=0.0009) and current smoking (0.0021) were significant predictors of lung cancer morbidity. CONCLUSIONS: Asbestosis patients with radiographic progression of small opacity profusion over a few years are at a higher risk of lung cancer than those with a less aggressive course of the disease. The progression of pulmonary fibrosis may be an independent risk factor that, in addition to smoking history and the intensity of asbestos exposure, could be used to estimate lung cancer risk.

pH-dependent binding of Helicobacter pylori to pig gastric mucins.

A microtiter-based assay was developed to study the binding of Helicobacter pylori to pig gastric mucins purified by density-gradient centrifugation in CsCl/4 M guanidinium chloride. Binding of H. pylori was observed over the 'mucin' band as well as with 'low-density' components in the gradients, and binding to the latter was more pronounced when incubations were performed at 37 degrees C as compared to 20 degrees C. At a lower pH, binding of H. pylori (strain SVA 40) to the 'high-density' mucins from pig antrum was increased but binding to the 'low-density' ones was decreased. Binding of the P466 strain (Le(b)-specific) was mainly associated with the 'mucin' band, whereas the MO19 strain reacted preferentially with the 'low-density' components. In summary, H. pylori may bind to gastric mucins and the binding is influenced by temperature, pH and the repertoire of bacterial adhesins.

Occurrence of asthma and chronic bronchitis among female hairdressers. A questionnaire study.

We carried out a retrospective cohort study using a self-administered questionnaire to assess the risk of hairdressers to develop asthma and chronic bronchitis. A representative sample of 4433 female hairdressers and an equal number of shop personnel in employment in 1980 was drawn from the Longitudinal Census Data File of Statistics Finland. Physician-diagnosed asthma, chronic bronchitis, and other respiratory diseases in 1980 and 1995 were inquired about in the respiratory part of the questionnaire. The response rate to the questionnaire was 82% for the hairdressers (n = 3484) and 79% for the referents (n = 3357). The prevalence of asthma among the hairdressers was 5.6% in 1980 and 10.1% in 1995, and the prevalence of chronic bronchitis was 3.9% in 1980 and 5.6% in 1995. The relative risk for asthma (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.3 to 2.3 in 1980; and OR: 1.7, 95% CI: 1.4 to 2.2 in 1995) and for chronic bronchitis (OR: 2.2, 95% CI: 1.5 to 3.2 in 1980; and OR: 1.9, 95% CI: 1.4 to 2.6 in 1995) among hairdressers was almost twice that in the reference group. The incidence rate of asthma in 1980 through 1995 was 2.2 and of chronic bronchitis was 1.1 cases per 1000 person-years among hairdressers, whereas the rate in the reference group was 1.3 asthma cases and 0.9 chronic bronchitis cases per 1000 person-years. The relative risk for developing asthma during the 15 years observation time was 1.7 (95% CI: 1.1 to 2.5) and for chronic bronchitis was 1.2 (95% CI: 0.7 to 1.9) among hairdressers, compared with referents. Our results indicate that hairdressers are at higher risk for developing asthma.

Occupational asthma--time for prevention.

Incidence figures show that occupational asthma is increasing. It often takes a deteriorating course. Follow-up studies of workers suffering from the disease have uniformly reported persistence of symptoms over long periods, even among formerly exposed workers. New initiators of occupational asthma are continuously being reported. Still "old" agents, such as diisocyanates and flours, remain major causes. There seems to be some disconnection in the dialogue between the medical and the technical parties involved. For prevention, it is essential to ensure that important information not only reaches those who are responsible for designing and maintaining processes, but that it is presented in an intelligible form. Occupational asthma has become an important occupational disease that merits high priority. Recent achievements should facilitate preventive actions. However, prevention is a multidisciplinary enterprise needing the commitment of industrial hygienists and engineers, chemists, and allergologists, in addition to that of occupational health personnel.

Atopy and work.

Atopy denotes the exceptional capacity to produce immunoglobulin (Ig)E antibody when exposed to common environmental allergens. The characteristic is frequently used for preemployment screening purposes. Too little attention has, however, been paid to the rationale and the consequences of this practice. Atopy is very common, and so decisions made because of atopy probably affect about a third of the working population. Work-related hypersensitivity symptoms cannot be eradicated by the weeding out of atopics. The intensity of exposure and/or the sensitizing properties of causative agents are often extremely strong in occupational settings and trigger the production of specific IgE antibodies even in nonatopics. Atopy is probably not sufficiently discriminative for screening purposes even in environments where atopics are known to have a greater risk of developing asthma (eg, laboratories with animals). Moreover, weeding out atopics may be used instead of hygienic and technical measures to reduce exposure levels. Separate decisions on medical, as well as legal, grounds may be warranted when a person with atopic symptoms, ie, rhinitis, asthma, or dermatitis, enters a new occupational environment. There is an urgent need for prospective studies in various occupational environments.

Respiratory symptoms, pulmonary function and allergy to fur animals among fur farmers and fur garment workers.

OBJECTIVES: This study determined the prevalence of respiratory symptoms and immediate hypersensitivity to fur allergens among fur farmers and fur garment workers and measured the pulmonary function of these groups of workers. METHODS: Fur farmers (N=188) and fur garment workers (N=175) were compared with workers in a factory producing polyvinyl products (N=181) and bank and health center workers (N=118), respectively. The groups were given a self-administered questionnaire, lung function tests (spirometry, diffusing capacity), and skin prick tests to common environmental allergens, and epithelium (hair) and urine of fur animals. RESULTS: Rhinitis symptoms and eye complaints were significantly more common among the fur garment workers than among their referents, but were not associated with atopy. Between the fur farmers and their referents, the symptom prevalence did not differ significantly. Smoking explained the lower forced vital capacity and forced expiratory volume in 1 second of the fur garment workers. The prevalence of positive skin tests did not differ significantly between the exposed group and their respective referents. The skin tests showed cross-reactivity between antibodies to fur and domestic animal allergens. As confirmed by a questionnaire sent to former fur workers, selection took place for both groups of fur workers. CONCLUSIONS: Fur garment workers have an excess of rhinitis and eye symptoms, which primarily appear to be nonimmunologic. Allergy to fur animals forces sensitized workers, especially asthmatics, to leave the trade. A supplementary questionnaire to former workers on pertinent exposures and reasons for leaving a particular job can be recommended for use in prevalence studies.

A thirteen-year follow-up of respiratory effects of acute exposure to sulfur dioxide.

OBJECTIVES: In 1977, nine men were accidentally exposed to sulfur dioxide in an explosion in a pyrite mine. The lung function of seven men was followed after the accident. A four-year follow-up has been published previously. The greatest decrease in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and maximal midexpiratory flow (MMEF) was observed one week after the accident, after which all these parameters improved without reaching the preaccident level. Reversible bronchial obstruction was still present in three patients, and a positive reaction in the histamine challenge test was found for four. In the present paper, the lung function follow-up 13 years after the accident is reported for six men. METHODS: The patients' clinical condition, chest X-ray, spirometry, and histamine challenge test were studied 13 years after the incident. RESULTS: Spirometry was normal in one worker, two displayed obstruction, and three had a combined obstructive and restrictive, mainly obstructive, ventilatory impairment. In the histamine challenge test, four patients showed bronchial hyperreactivity, one with a nearly significant reaction. Because of bronchial obstruction one patient could not perform the challenge test. CONCLUSIONS: This 13-year follow-up showed that acute inflammatory obstruction caused by exposure to sulfur dioxide left, as sequelae, obstructive impairment of ventilatory function and permanent bronchial hyperreactivity. The clinical picture displayed by these patients was named the "reactive airways dysfunction syndrome" (RADS) in 1985. Four of the patients also showed symptoms of chronic bronchitis.

Respiratory status of stainless steel and mild steel welders.

Eighty-three full-time stainless steel and 29 mild steel welders from one shipyard were examined clinically, and their lung function was measured. The stainless steel welders had used both tungsten inert-gas (low-fume concentration) and manual metal-arc (MMA) (high-fume concentration) welding methods. The individual exposure of the welders was estimated based on the time spent doing MMA welding, the amount of retained contaminants in the lungs (magnetopulmography), and urinary chromium excretion. The results suggest that there is a greater prevalence of small airway disease among shipyard mild steel MMA welders than among stainless steel welders. Among the stainless steel welders the impairment of lung function parameters was associated with the MMA welding method. The type of welding, then, is important when the health hazards of welders are studied, and welders cannot be regarded as a single, homogeneous group.

Sensitization to industrial enzymes in enzyme research and production.

OBJECTIVES: This study investigated sensitization to industrial enzymes in Finnish enzyme production and in Finnish laboratories. METHODS: A cross-sectional study was conducted in 2 plants producing industrial enzymes and in their product development and research laboratories. Sensitization to enzymes and environmental allergens was examined by skin prick tests and specific immunoglobulin E determinations (radioallergosorbent test). The employees were interviewed for work-related respiratory symptoms. Altogether 173 employees were examined. RESULTS: The skin prick test showed 21 employees (12%) to be sensitized to one or more enzymes. Sixteen positive persons also had specific immunoglobulin E. Atopy was distinctly associated with enzyme sensitization. An exposure-response relationship was found for enzyme sensitization and for respiratory symptoms during work. For sensitization, the exposure-response linear trend was statistically significant. It weakened but remained statistically significant after stratification for atopy. For symptoms, likewise, the exposure-response linear trend was statistically significant, and the statistical significance remained after stratification for atopy. CONCLUSION: The study confirmed that industrial enzymes are potent sensitizers. The handling of dry enzymes in laboratory work may cause sensitization. Sensitization may even follow minute degrees of exposure, such as among office personnel. Atopics are more susceptible to sensitization than nonatopics. Nonatopics are also clearly at risk; the demonstrated exposure-response relationship emphasizes the need for and advantages of proper exposure control.

Fibrosis of the lung and pleura and long-term exposure to wollastonite.

OBJECTIVES: The purpose of this study was to determine whether long-term exposure to wollastonite causes fibrosis of the lung and pleura in humans. METHODS: Forty-nine workers (mean exposure 25 years) in a Finnish limestone-wollastonite mine and mill were examined. Their work histories and symptoms of chronic bronchitis were recorded. The chest radiographs were classified according to the classification of the International Labour Office (1980); a radiographic follow-up from 1981 to 1990 was included. Spirometry and diffusion capacity were measured. Four workers underwent high-resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL). Lung tissue specimens were available for 2 workers. Mineral fibers and asbestos bodies were analyzed from the BAL fluid and lung tissue specimens, which were also analyzed for lung fibrosis. RESULTS: Two workers (4%) had small irregular lung opacities (ILO 1/0), 1 worker (2%) ILO 0/1 of the s/t type. HRCT revealed no parenchymal fibrosis in the 2 workers with the ILO 1/0 classification. Of the 9 workers (18%) with pleural plaques, 5 had been exposed to asbestos. Multivariate logistic regression analyses revealed no association of plaques with the duration of wollastonite or asbestos exposure. Wollastonite fibers or bodies were not found in any of the 4 workers who underwent BAL, nor in either of the workers whose lung tissue specimens were available. CONCLUSIONS: No evidence was found that long-term exposure to wollastonite causes parenchymal fibrosis of the lung and pleura. Furthermore, the findings indicate that wollastonite fibers are poorly retained in human lungs.

Cellulase allergy and challenge tests with cellulase using immunologic assessment.

OBJECTIVES: This study attempted to develop and evaluate a challenge test for diagnosing allergic asthma and rhinitis due to cellulase. METHODS: Challenge tests in a chamber were performed on 11 persons sensitized to cellulase. Four different enzyme-lactose mixtures, starting from a 0.03% mixture, were used. The enzyme dust was generated from a dry enzyme preparation mixed with lactose powder, using pressurized air. The cellulase concentration in the air was measured with an immunochemical method. RESULTS: Nasal, pharyngeal, or bronchial symptoms could be elicited at cellulase air concentrations of 1 to 1300 microg/m3. A dose-response relationship was observed for symptoms in repeated challenge tests with increasing concentrations of cellulase. For 2 persons skin symptoms could also be reproduced. CONCLUSION: The challenge method proved to be a practical means with which to simulate conditions at the worksite and elicit the specific respiratory symptoms of the patients.

Blood lead levels in Finnish preschool children.

The blood lead (Pb-B), hemoglobin and hematocrit were measured in 286 Finnish children living in the three largest cities of Finland (n = 172), in rural areas (n = 54) and in a lead smelter area (n = 60). Pb-B was determinated using an atomic absorption spectrophotometric micro method. The precision of the method was good, as was the accuracy tested by an international interlaboratory comparison. The mean Pb-B in urban, rural and lead smelter areas varied between 6.0 - 6.7 microgram/100 ml** (range 3 - 17 microgram/100 ml) and there were no significant differences between the residential areas. The mean values of hemoglobin and hematocrit were in the normal range. The Pb - B values in Finnish children studied were low compared with many international studies but at a similar level as in some recent Scandinavian studies.