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.

Occupational asthma caused by stainless steel welding fumes: a clinical study.

The aim of the present study was to describe the cases of occupational asthma (OA) due to stainless steel welding fumes diagnosed at the Finnish Institute of Occupational Health during the period 1994-2003. OA was diagnosed according to patient history, lung function examinations and welding challenge tests with measurements of the forced expiratory volume in one second (FEV(1)) and peak expiratory flow (PEF) values. The present series comprised 34 patients, all male, with a mean age of 44.7 yrs (range 22-57), mainly working as welders. The mean duration of exposure was 22.4 yrs, and the mean duration of exposure before the onset of respiratory symptoms was 18 yrs. Dyspnoea was the most frequently reported work-related respiratory symptom. During the inhalation challenge tests, the mode of the asthmatic FEV(1)/PEF reaction was delayed in 16 (47%) patients, immediate in nine (26%) patients and dual (both immediate and delayed) in nine (26%) patients. In the follow-up assessment 6 months later, only six patients were considered able to continue performing welding tasks, whereas occupational injury pension was recommended for seven, and measures of vocational rehabilitation for 14 patients. In most cases, after the diagnosis of occupational asthma, the continuation of welding work was not possible.

IgG4 response to fur animal allergens among fur workers.

OBJECTIVE: The aim of this study was to determine whether IgG(4) antibodies to allergens in urine extracts from fur animals associated with positive prick tests to the same allergens and with the occurrence of respiratory symptoms among fur workers, especially among highly exposed fur farmers. METHODS: Among the fur workers and among their referents, IgG(4) antibodies to mink and silver fox urine were analysed in three groups; all workers with a positive skin prick test to any fur animal allergen (n=50), all workers who had reported shortness of breath or rhinitis or eye symptoms (n=159), and to a random sample of asymptomatic persons (n=178). In the two last groups none of the workers had a positive skin test to any fur animal allergen. RESULTS: The fur farmers had higher level of IgG(4) values than other groups and also had positive IgG(4) antibodies to urine extract more frequently than the other groups. Among the exposed subjects, there was a distinct overlapping of a positive skin prick test to fur urine allergens and positive IgG(4) antibodies to responding allergens. Among the fur farmers the IgG(4) levels were associated with symptoms. CONCLUSIONS: IgG(4) antibodies were shown to be a good indicator of exposure. Because of an overlapping of positive skin prick tests and IgG(4) response to the same allergens, and an association between symptoms and IgG(4) response, it is recommended that the potential role of IgG(4) antibodies as an indicator of alternative sensitisation should be further examined in prospective studies.

Controversies in epidemiology of occupational asthma.

Epidemiology is the study of the distribution, determinants and outcome of disease. In this article, the recently acquired knowledge of the epidemiology of occupational asthma is described, as well as current areas of controversy. Incidence figures obtained from field studies in high-risk workplaces, medicolegal statistics and sentinel programmes indicate that approximately 10% of adult-onset asthma is attributable to the workplace. The strategy to identify cases through questionnaires and tools that address functional, immunological and physiopathological issues needs to be improved. Although few in number and limited to a handful of workplaces, cohort studies found that the risk of developing occupational asthma is determined less by individual susceptibility (e.g. atopy, tobacco smoking, human leukocyte antigen phenotype) and more by the level of exposure to its causes; in general, the higher the exposure, the greater the risk, and, by implication, lowering the level of exposure reduces the incidence of disease. Occupational asthma can be used as a satisfactory model for the development of adult-onset asthma. There is a great need to develop intervention strategies through adequate surveillance programmes in high-risk workplaces.

Turbulent particle transport in magnetized plasmas.

Particle transport in magnetized plasmas is investigated with a fluid model of drift wave turbulence. An analytical calculation shows that magnetic field curvature and thermodiffusion drive an anomalous pinch. The curvature driven pinch velocity is consistent with the prediction of turbulence equipartition theory. The thermodiffusion flux is found to be directed inward for a small ratio of electron to ion pressure gradient, and it reverses its sign when increasing this ratio. Numerical simulations confirm that a turbulent particle pinch exists. It is mainly driven by curvature for equal ion and electron heat sources. The sign and relative weights of the curvature and thermodiffusion pinches are consistent with the analytical calculation.

Exhaled nitric oxide in specific challenge tests to assess occupational asthma.

Exhaled nitric oxide (NO) is a marker of eosinophilic inflammation of the airway mucosa accompanying changes in the clinical condition of asthma. Allergen exposure has been associated with delayed elevation of exhaled NO. The aim of this study was to assess the asthmatic airway inflammation with exhaled NO measurements during specific bronchial challenge tests with occupational agents. Forty patients with suspected occupational asthma were investigated. Specific bronchial challenge tests were performed with forced expiratory volume in one second or peak expiratory flow follow-up, supplemented by exhaled NO measurements before and 24 h after challenge tests. In active challenges, which induced bronchoconstriction, a significant mean increase of exhaled NO concentration was noted. In patients with a normal or slightly increased (<14.5 parts per billion (ppb)) basal NO level and a late bronchoconstriction, a significant increase in exhaled NO was seen. Patients with a high basal NO level (>14.5 ppb) and a significant bronchoconstriction did not show a significant NO elevation. Challenge tests without bronchoconstriction were not associated with a significant elevation of exhaled NO. Exhaled nitric oxide measurements can be used to indicate the development of airway inflammation accompanying late asthmatic reaction after bronchial challenge tests in patients with a normal or slightly increased basal nitric oxide concentration.

Phthalic anhydride allergy: development and characterization of optimized hapten-carrier conjugates for improved diagnosis.

BACKGROUND: At present the diagnosis of IgE-mediated hypersensitivity to phthalic anhydride (PA) is based on conjugates that are not characterized or standardized. The aim of this study was to develop optimized and molecularly characterized PA conjugates that can be used to improve the diagnosis of PA-allergy. METHODS: The PA conjugates were synthesized and the number of haptens bound on a carrier protein was estimated by matrix-assisted laser desorption/ionization time of light (MALDI-TOF) mass spectrometry. The ability of conjugates to bind IgE and IgG antibodies was measured by enzyme-linked immunosorbent assay (ELISA). Reactivity of the conjugates in vivo was evaluated by skin prick testing. RESULTS: The most active IgE-binding conjugates had a PA : HSA molar ratio of 80 : 1. In the optimal conjugates the average numbers of PA haptens per carrier molecule of human serum albumin (HSA) were 14-16. In ELISA, all 13 patients and none of the 20 controls had IgE antibodies to optimized PA conjugate. The sensitivity and specificity of the ELISA was comparable to commercial CAP RAST. PA conjugates elicited positive test results in skin prick testing showing that conjugates are immunologically active also in vivo. CONCLUSIONS: These results indicate that optimized and molecularly characterized PA-HSA conjugates can be used both in vitro and in vivo assays to improve the diagnosis of PA allergy.

Immunoglobulin G antibodies against indoor dampness-related microbes and adult-onset asthma: a population-based incident case-control study.

Immunoglobulin G (IgG) antibodies against microbes related to indoor dampness problems have been used as potential biomarkers of fungal exposure in clinical investigations. There is limited information on their relation to asthma. We conducted a population-based incident case-control study to assess the risk of asthma in relation to specific IgG antibodies to eight dampness-related microbes: Aspergillus fumigatus, A. versicolor, Cladosporium cladosporioides, Fusarium oxysporum, Sporobolomyces salmonicolor, Stachybotrys chartarum, Streptomyces albus and Trichoderma citrinoviride. We recruited systematically all new cases of asthma during a 2.5-year study period and randomly selected controls from a source population of adults 21-63 years of age living in the Pirkanmaa Hospital District, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls selected randomly from the source population. IgG antibodies were analysed with ELISA. An increased risk of developing asthma in adulthood was significantly related to IgG antibodies to T. citrinoviride, but not to the other moulds. There was no evidence of a dose-response relation between the IgG antibody level and the risk of asthma. T. citrinoviride may play a role in the aetiology of adult-onset asthma or serve as an indicator of other causal factors.

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.

Sensitisation to enzymes in the animal feed industry.

OBJECTIVES: To assess the prevalence of enzyme sensitisation in the animal feed industry. METHODS: A cross sectional study was conducted in four animal feed factories, where several enzymes had been used in powder form for 7-9 years. Before this study, enzymes in liquid form had started to be used. Sensitisation to enzymes was examined by skin prick and radioallergosorbent (RAST) tests. Altogether 218 workers were tested; 140 people in various tasks in manufacturing, where exposure to various organic dusts and to enzymes was possible, and 78 non-exposed office workers. The workers were interviewed for work related respiratory and skin symptoms. Total dust concentrations were measured by a gravimetric method. The concentrations of protease and alpha-amylase were measured with catalytic methods and that of xylanase with an immunological method. RESULTS: Ten workers (7%) were sensitised to enzymes in the exposed group of 140, whereas none were sensitised in the non-exposed group. Six of the sensitised people had respiratory symptoms at work: two of them especially in connection with exposure to enzymes. Enzyme concentrations in the air varied greatly: xylanase from less than 0.8 ng/m(3) up to 16 ng/m(3), alpha-amylase from less than 20 ng/m(3) up to 200 ng/m(3), and protease from less than 0.4 ng/m(3)up to 2900 ng/m(3). On average, highest xylanase and alpha-amylase concentrations were found in the various manufacturing sites, whereas the highest protease concentrations were found in areas of high total dust. CONCLUSIONS: Industrial enzymes may cause allergies in the animal feed industry. There is a need to assess exposure to enzymes at various phases of production, and to minimise exposures.

Long-term follow-up of hexamethylene diisocyanate-, diphenylmethane diisocyanate-, and toluene diisocyanate-induced asthma.

In 1976-1992 245 new cases of asthma induced by diisocyanates were diagnosed, caused by hexamethylene diisocyanate (HDI) in 39%, diphenylmethane diisocyanate (MDI) in 39%, and toluene diisocyanate (TDI) in 17% of the cases. Our aim was to study the clinical outcome of diisocyanate-induced asthma. A questionnaire was sent to the 235 patients alive in 1995, and validated by reexamining clinically 91 of them. The study was carried out on average 10 () yr after the diagnosis. Of the patients 82% experienced symptoms of asthma, 34% used no medication, and 35% were on regular medication. The patients having displayed immunoglobulin E (IgE) antibodies to isocyanates used less medication (OR 0.273; CI 0.098, 0.758) and had fewer symptoms of asthma (OR 0.329; CI 0.124, 0.875) than the IgE-negative ones. They also had a significantly shorter duration of symptoms (p = 0.0025), latency period (p = 0.0249), and duration of exposure (p = 0.0008) than the IgE-negative patients. This did not, however, entirely explain the more favourable outcome of the IgE-positive patients. Patients with HDI-induced asthma used less medication (OR 0.412; CI 0.229, 0.739) than patients with MDI- and TDI-induced asthma. The results confirm the generally rather poor medical outcome of diisocyanate-induced asthma; the persistence of symptoms and unspecific bronchial reactivity were pronounced in TDI-induced asthma. A more favourable outcome was associated with IgE mediation and HDI inducement.

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.

Risk of enzyme allergy in the detergent industry.

OBJECTIVES: To assess the prevalence of enzyme sensitisation in the detergent industry. METHODS: A cross sectional study was conducted in a detergent factory. Sensitisation to enzymes was examined by skin prick and radioallergosorbent (RAST) tests. 76 Workers were tested; 40 in manufacturing, packing, and maintenance, and 36 non-exposed people in management and sales departments. The workers were interviewed for work related respiratory and skin symptoms. Total dust concentrations were measured by a gravimetric method, and the concentration of protease in air by a catalytic method. RESULTS: Nine workers (22%) were sensitised to enzymes in the exposed group of 40, whereas none were sensitised in the non-exposed group. All the sensitised people had symptoms at work; all had rhinitis and one had asthma. Protease concentrations were generally < 20 ng/m3, but occasional peak values up to 80 ng/m3 were detected in the packing and maintenance tasks, and high values of > 1 microgram/m3 in the mixing area. CONCLUSION: Despite the use of encapsulated enzyme preparations, high enzyme concentrations in workplace air are possible, resulting in a higher risk of sensitisation than expected.

Incidence of occupational asthma by occupation and industry in Finland.

BACKGROUND: Systematic research on occupation or industry-specific incidence of occupational asthma (OA) is sparse. We calculated the incidence of notified OA by occupation, industry and causative agent in Finland for the years 1989-95. METHODS: The numbers of cases of reported OA were retrieved from the Finnish Registry of Occupational Diseases for the population between 20 and 64 years of age. The numbers of employed workers were retrieved from Statistics Finland. Incidence rates were calculated for each occupation, industry and the total workforce. RESULTS: Altogether 2602 cases of OA were notified and the mean annual incidence rate was 17.4 cases/100,000 employed workers. The incidence rate was the highest in bakers, other painters and lacquerers, veterinary surgeons, chemical workers, farmers, animal husbandry workers, other food manufacturing workers, welders, plastic product workers, butchers and sausage makers, and floor layers. Cases caused by animal epithelia, hairs and secretions or flours, grains, and fodders accounted for 60% of the total. CONCLUSIONS: Estimation of occupation and industry-specific incidence rates forms the basis for successful prevention of OA, but necessitates collection of data over several years from well-established surveillance systems.

Lung sounds in asbestos induced pulmonary disorders.

The aim of the study was to compare the lung sounds in patients with asbestos related pulmonary disorders with findings in high-resolution computed tomography (HRCT), and with lung function variables, in order to find out associations of acoustic changes with radiological fibrosis, emphysema or with pulmonary gas transfer functions. Sixty-four patients with asbestos-related pleural disease, with or without pulmonary disease, were studied. Lung sound recording and analysis was carried out with a computerized lung sound analyser, and HRCT of the chest, as well as forced spirometry and diffusing capacity measurement were performed. The fibrosis score correlated positively with the quartile frequencies of the power spectrum of lung sounds in inspiration (f50) and expiration (f50) and crackle count in inspiration, as well as negatively with diffusing capacity. When the patients with crackling sounds and significant fibrosis were excluded (n=18), emphysema correlated negatively with expiratory quartile frequencies of the power spectrum, with f25 and f50. Furthermore, diffusing capacity correlated with inspiratory f25 and forced expiratory volume in one second with inspiratory f50 when crackles and fibrosis were excluded. Changes in lung sounds were significantly associated with radiologically verified abnormalities and gas transfer of pulmonary tissue. High sound frequencies were associated with fibrotic changes of the lung while low sound frequencies with pulmonary emphysema. Acoustic analysis gives complementary clinical information for evaluation of asbestos-related pulmonary disorders.

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.

Occupational respiratory hypersensitivity caused by preparations containing acrylates in dental personnel.

BACKGROUND: Allergic contact dermatitis caused by acrylate compounds is common in dental personnel; they also often complain of work-related respiratory or conjunctival symptoms. OBJECTIVE: The aim of the present study was to report the cases of acrylates induced respiratory hypersensitivity in dental personnel diagnosed in Finland during the last 6 years. METHODS: Occupational asthma, rhinitis, laryngitis and pharyngitis cases were diagnosed according to patient history, PEF monitoring, and a work-simulating provocation test. RESULTS: Twelve cases of respiratory hypersensitivity caused by acrylates diagnosed in dental personnel (six dentists and six dental nurses) in 1992-97 are reported. During this period one case of conjunctivitis and one of laryngitis have been published separately. Nine cases of occupational asthma, two rhinitis cases, and one laryngitis case were verified according to the challenge tests with dental acrylate compounds (acrylates, methacrylates and epoxy acrylates). Only three patients had positive skin-prick test reactions to common environmental allergens, and none reacted to acrylates in the skin-prick tests. Five patients had an elevated total IgE (>110 kU/L). PEF follow-up showed an occupational effect in all examined eight patients with diagnosed asthma. The mean duration of exposure to acrylates was 22 years, and the duration of respiratory symptoms 8 years. CONCLUSIONS: The results indicate that acrylates constitute an important hazard for dental workers. The mechanism of respiratory hypersensitivity is still unknown, and it is probably not IgE-mediated.