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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.

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 μg 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.

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.

An erratum has been added to this article. It can be viewed in Gastroenterology 2003;124:588 Background & Aims: In the stomach, Helicobacter pylori is found both in the mucus layer and adhering to the gastric epithelium. The aim of this study is to characterize the binding of H. pylori to human gastric mucins. Methods: H. pylori strains that bind the Lewisb (Leb) structure (via the BabA adhesin) and/or sialylated structures, along with isogenic adhesion deletion mutants, were used to identify microbe-binding mucins. Gastric mucins from 5 healthy individuals, isolated by density-gradient centrifugation, were investigated for H. pylori binding at neutral pH using a microtiter-based technique. Results: H. pylori strains that express the BabA adhesins were shown to bind to the MUC5AC mucin in individuals expressing the Leb antigen. Further fractionation with an ion-exchange chromatography revealed Leb-positive MUC5AC glycoforms that differed in their receptor properties for different H. pylori strains. None of the H. pylori strains studied bound to mucins from Leb-negative individuals. However, all strains bound to low-density, nonmucin, Leb-negative material on top of the gradients. Conclusions: Binding of H. pylori to human gastric MUC5AC isolated from healthy individuals is BabA dependent and mediated by the Leb structure presented by the mucin. However, the BabA adhesins demonstrate strain-dependent preference in binding to MUC5AC glycoforms substituted with Leb, allowing for great interindividual variability in host–microbe interactions. GASTROENTEROLOGY 2002;123:1923-1930

SUMMARY 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.

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-tran

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 α-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/m3 up to 16 ng/m3, α-amylase from less than 20 ng/m3 up to 200 ng/m3, and protease from less than 0.4 ng/m3up to 2900 ng/m3. On average, highest xylanase and α-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. Keywords: animal feed; enzyme allergy; occupational exposure

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.

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 mg/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.

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 1 µg/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. Keywords: detergent enzymes; occupational exposure; allergy

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.

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.

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 exsmokers. 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.

Pig gastric mucins were isolated from the surface epithelium of the cardiac region, corpus and antrum using density-gradient centrifugation after extraction in 6 M guanidinium chloride. In CsCl/0.5 M guanidinium chloride, mucins solubilized from the cardiac region appeared as a broad unimodal band at 1.52 g/ml whereas those from the corpus and antrum occurred as high- and low-density populations at 1.50 and 1.45 g/ml respectively. High-iron diamine reacted more strongly with the cardiac mucins and the high-density populations from corpus and antrum than with the two low-density ones. In keeping with this, approx. 60% of the oligosaccharides from the former mucins and 20% from the latter contained sulphate. All surface epithelial cells of the cardiac region stained with high-iron diamine, whereas in the corpus only the epithelium in the bottom of the pits reacted, suggesting that the high-density population from this region originates from these cells. Mucins from all regions were composed of subunits, each containing highly glycosylated domains. The mucins from the cardiac region were larger than those from the corpus and antrum, and reduced subunits as well as high-molecular-mass glycopeptides from the cardiac mucins were larger than the corresponding fragments from the other regions. Ion-exchange HPLC showed that reduced subunits from the cardiac mucins and the high-density populations from the corpus and antrum were more ‘acidic’ than reduced subunits from the two low-density ones. All mucins contained a ‘neutral’ fraction, in particular those from the antrum. Pig gastric mucus thus contains a number of distinctly different mucin populations varying in buoyant density, size, ‘acidity’, glycosylation, sulphation and tissue origin.

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.

Summary Background Polyester powder paints are extensively used in metal painting. Triglycidyl isocyanurate (TGIC), an epoxy compound, is often used as a hardener. Several cases of allergic eczema from occupational exposure to TGIC have been reported in the literature. Objective We examined a 36-year-old non-smoking man who worked mainly as a spray painter, using a polyester powder paint containing 4% TGIC. During painting he used protective clothing and a motorized breathing protector. After 4 years he developed eczema on his hands, face and body, and an occupational allergic eczema caused by TGIC was diagnosed. He also suffered from powder-paint-related asthmatic symptoms. Objective Occupational asthma was diagnosed in accordance with the accepted guidelines. Inhalation challenge tests were performed with the paint and TGIC Results Spirometry showed slight obstruction; the blood eosinophils and serum IgE value were elevated. Skin-prick tests with common environmental allergens were negative. The challenge test with lactose powder was also negative, A challenge test with a paint containing TGIC (4%) induced a dual reaction in PEF and a late 23% fall in FEV,. A test with TGIC (4%) mixed with lactose induced a dual PEF reaction, and also dual changes in spirometry. The PD15 in the histamine challenge test decreased significantly after the challenge tests. Conclusions To our knowledge this is the first diagnosed case of occupational asthma caused by TGIC. This case report emphasizes the importance of protecting both the skin and respiratory tract of workers against chemicals such as TGIC, capable of causing skin and respiratory allergy.

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 parenchymal fibrosis in the 2 workers with the ILO 1/0 of the s/t type. 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.

Acoustic rhinometry (ARM) has been used to study the nasal cavity geometry and the response in nasal provocations. However, the use of ARM in the diagnosis of occupational rhinitis (OR) has not been reported. The purpose of this study was to find an ARM parameter and a limit value that could be used in provocation tests to express an objective change in the nasal cavity geometry. We used a new calculated parameter, Volume MCA%, for describing the change in the nasal geometry. Volume MCA% is the mean of the percentile changes of nasal volumes and minimal cross-sectional areas in a provocation test. We recommend a decrease of at least 15% in Volume MCA% for the limit of an essential change in the nasal cavity.

Epidemiological evidence shows that indoor dampness is associated with respiratory symptoms, the aggravation of preexisting asthma, and the development of new-onset asthma. Follow-up studies indicate that symptoms compatible with asthma constitute risk factors for the future development of asthma. The aims of the study were (1) to assess whether asthma-like symptoms (cough, dyspnea, and wheeze) that occur in relation to exposure to damp and moldy work environments lead to the later development of asthma and (2) to assess the importance of continued exposure to indoor dampness and molds at work in the development of asthma. We followed 483 patients with asthma-like symptoms related to damp workplaces but without objective evidence of asthma in baseline examinations. The development of asthma and present work conditions were established with the use of a questionnaire 3–12 years later. A total of 62 patients (13%) reported having developed asthma during the study period. Continued exposure to a damp or moldy environment was associated with a more than fourfold increase in the risk of asthma (odds ratio 4.6, 95% confidence interval 1.8–11.6). Working in a non-remediated environment at follow-up was the strongest risk factor for developing asthma. The remediation of damp buildings seemed to be associated with a decrease in the risk of asthma. The results indicate that exposure at work to dampness and molds is associated with the occurrence of new-onset asthma. Exposed workers suffering from asthma-like symptoms represent a risk group for the development of asthma. The risk appears especially high if the exposure continues. Due to inherent weaknesses of patient series, the findings need corroborative studies.

The consequences of occupational asthma (OA) in terms of health, quality of life and costs incurred for the individual as well as society are considerable and make prevention worthwhile. The majority of cases are caused by comparatively few major asthmagens, such as flour dust, animal epithelium, natural rubber latex, and diisocyanates. A substantial reduction of these exposures is a realistic objective. It is important that preventive strategies are undertaken as concerted actions by all actors involved, i.e. regulatory authorities, branch organisations and worker unions. However, many asthmagens only cause occasional cases. Understandably, the prevention of these will rarely be highly prioritised. Aggravation of any asthma by non-specific exposures at work (work-exacerbated asthma, WEA) has turned out to be as important as OA. The costs incurred by WEA as well as the effects on quality of life equal or surpass those of OA. So far, our understanding of the nature of WEA as compared with OA is poor and far too meagre for scientifically based preventive strategies. Future research needs to focus on practically all aspects of WEA.

Damp and moldy indoor environments aggravate pre-existing asthma. Recent meta-analyses suggest that exposure to such environments may also induce new-onset asthma. We assessed the probability of molds being the cause of asthma in a patient series examined because of respiratory symptoms in relation to workplace dampness and molds. Altogether 694 such patients had been clinically assessed between 1995 and 2004. According to their histories, they had all been exposed to molds at work and had suffered from work-related lower respiratory symptoms. The investigations had included specific inhalation challenge (SIC) tests with mold extracts and serial peak expiratory flow (PEF) recordings. Using internationally recommended diagnostic criteria for occupational asthma (OA), we categorized the patients into three groups: probable, possible, and unlikely OA (156, 45, and 475 patients, respectively). The clinical details of 258 patients were analyzed, and their levels of microbial exposure were evaluated. The agreement between the serial PEF recordings and SIC tests (both being either positive or negative) was 56%. In the group of probable OA, mold sensitization was found in 20%. The level of exposure and sensitization to molds was associated with probable OA. At 6 months, the follow-up examinations of 136 patients with probable OA showed that the symptoms were persistent, and no improvement in spirometry was noted despite adequate treatment. Only 58% of the patients had returned to work. Exposure to damp and moldy workplaces can induce new-onset adult asthma. IgE mediation is a rare mechanism, whereas other mechanisms are unknown.

Background Numerous studies confirm the association between exposure to indoor air dampness and molds and different health outcomes. Of these, upper respiratory tract problems are the most commonly reported work-related symptoms in damp indoor environments. The aim of this study was to describe a clinically investigated patient series with occupational rhinitis induced by molds. Methods Nasal provocation test (NPT) with commercial fungal allergens was performed in 369 patients during 1995–2004 at the Finnish Institute of Occupational Health. Of these, 60 (16%) were positive. In addition to positive NPT, the diagnosis of occupational rhinitis was based on verified exposure to molds, work-related nasal symptoms, and clinical investigations. We wanted to review the patient files of these 60 patients retrospectively, and 56 patients gave their informed consent. Results The mean age of the patients was 43.7 years (SD ∓ 9.5). Fifty (89.3%) patients were women. In 23% of the patients, IgE-mediated allergy to molds could be established. Atopy significantly increased IgE sensitization to molds (OR, 10.3 [95% CI, 2.0–52.5]). The most common mold to induce occupational rhinitis was Aspergillus fumigatus. Exposure time was over 5 years in 63% of the patients. Association between the IgE sensitization to molds and exposure level was statistically significant (Fisher's exact test, p = 0.046). Conclusion This is the first clinically investigated series on occupational rhinitis in relation to a moldy environment. Based on our findings, we conclude that molds growing in conjunction with moisture damages can induce occupational rhinitis. IgE-mediated allergy to molds was not common. Atopy and significant exposure level increased IgE sensitization to molds. zri00508

We discuss quantitatively the capability of direct α-recoil to create observable radioactive disequilibrium (U-234/U-238 activity ratio > 1) in flowing groundwater. Coupled equations for radioactive decay chain are formulated for the solid U source and for the corresponding groundwater receiving the recoiling U-234 atoms. U-rich fracture coating material and the water flowing in the fracture are discussed in detail.The novel modelling approach worked well and provides a useful tool for more detailed site-specific studies with more detailed input data. The approach appears feasible because the equations are based on straightforward mass balance considerations.α-recoil -induced enrichment of U-234 in groundwater is a slow process: the increase of U-234/U-238 activity ratio to notable values above unity will take hundreds to thousands of years. Strong groundwater flow prevents any local recoil-induced U-234 enrichment in the water.

Occupational asthma has been found to be associated with lowered socio-economic outcomes, an increased unemployment rate and a decreased quality of life. The compensation of occupational diseases is comparatively favourable in Finland. Our aim was to follow-up the working status and life satisfaction of patients with diisocyanate-induced asthma in 245 cases diagnosed during 1976-1992. A questionnaire was sent out on average 10 (3-19) yr after the diagnosis to the surviving 235 patients. The questionnaire was validated by re-examining 91 of them clinically, and with spirometry, histamine challenge test and peak flow surveillance. Of the 213 responding patients, 14% were unemployed, and for 50% of them unemployment was caused by asthma. Unemployment was associated with nocturnal asthma symptoms (OR 10.93; CI 2.69-44.452), increased PEF variability (OR 8.46; CI 1.52-46.97) and with the use of short-acting beta-sympathomimetic medication (p=0.045). Satisfaction with life was associated with present working (OR 3.50; CI 1.73-7.06) and with good condition of asthma as assessed by the use of asthma medication (OR 0.49; CI 0.27-0.89) and objective measurements of the asthma condition, e.g. PEF variability (OR 0.21; CI 0.08-0.59). As a conclusion, unemployment was remarkably low as compared with earlier reports and related to the period of simultaneous economic recession. Unemployment, as well as dissatisfaction with life were associated with poor conditions of asthma. Unemployment was associated with improper asthma care favouring the use of short-acting beta-sympathomimetic medication. Proper follow-up of asthma is essential for minimizing the social complaints of occupational asthma, as well as for enhancing life satisfaction.

Objective: The aim of this study was to determine whether IgG4 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, IgG4 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 IgG4 values than other groups and also had positive IgG4 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 IgG4 antibodies to responding allergens. Among the fur farmers the IgG4 levels were associated with symptoms. Conclusions: IgG4 antibodies were shown to be a good indicator of exposure. Because of an overlapping of positive skin prick tests and IgG4 response to the same allergens, and an association between symptoms and IgG4 response, it is recommended that the potential role of IgG4 antibodies as an indicator of alternative sensitisation should be further examined in prospective studies.

Objectives The chlorofluorocarbons (CFC) used in refrigeration systems decompose on heating and produce substances that are highly irritating to the airways (eg, chlorine, carbonyl fluoride, and hydrogen fluoride). This study examined persistent respiratory symptoms among several workers exposed to thermal decomposition products of CFC. Methods Seven patients with respiratory symptoms caused by inadvertent exposure to thermal decomposition products of CFC in a restaurant kitchen or during refrigerator repair were studied with the use of spirometry, peak flow follow-up, and histamine challenge tests. Three patients also underwent bronchoscopy and bronchoalveolar lavage. Results In five of the cases, cough or dyspnea lasted longer than 1 month; for three of the five, the symptoms lasted more than 4 years. Three cases showed increased bronchial hyperreactivity, and two of the three had increased diurnal peak flow variation. Three patients fulfilled the criteria for acute irritant-induced asthma or reactive airway dysfunction syndrome. One case exhibited bronchiolitis while, for the other six, the clinical picture was consistent with bronchitis. Conclusions The studied cases indicate that the thermal decomposition products of CFC used in refrigerators may cause irritant-induced airway diseases of long duration.

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.

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.

We observed previously that polymorphisms in glutathione S-transferase (GST) genes modified allergic responses to diisocyanate exposure. Here, we extended the study to examine the possible role of N-acetyltransferase (NAT) genotypes in the development of diisocyanate-induced ill effects, both separately and in combination with the previously examined GSTM1, GSTM3, GSTP1 and GSTT1 genotypes. The study population comprised 182 diisocyanate-exposed workers, 109 of whom were diagnosed with diisocyanate-induced asthma and 73 of whom had no symptoms of asthma. The diisocyanates to which the workers had been exposed to were diphenylmethane diisocyanate (MDI), hexamethylene diisocyanate (HDI) and toluene diisocyanate (TDI). The NAT2 genotype did not have any significant effect on the risk of developing asthma, but the putative slow acetylator NAT1 genotypes posed a 2.54-fold risk of diisocyanate-induced asthma (95% confidence interval [CI] 1.32 to 4.91). The effect of the NAT1 genotype was especially marked for workers exposed to TDI, among whom the NAT1 slow acetylator genotypes posed a 7.77-fold risk of asthma (95% CI 1.18 to 51.6). Statistically significant increases in asthma risk were also observed among the whole study population for the concurrent presence of the GSTM1 null genotype and either NAT1 (odds ratio [OR] 4.53, 95% CI 1.76 to 11.6) or NAT2 (OR 3.12, 95% CI 1.11 to 8.78) slow acetylator genotypes, and of NAT1 and NAT2 slow acetylator genotypes (OR 4.20, 95% CI 1.51 to 11.6). The results suggest for the first time that in addition to GSTs, the NATs play an important role in inception of asthmatic reactions related to occupational exposure to diisocyanates.

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. Am. J. Ind. Med. 37:451–458, 2000. © 2000 Wiley-Liss, Inc.

OBJECTIVES: To determine whether occupational exposure to raw tobacco causes respiratory or allergic diseases, an excess of respiratory symptoms, a decrease in lung function, or parenchymal changes in chest radiography among Finnish cigar workers. METHODS: This cross sectional study included all Finnish cigar workers (n = 106) exposed to raw tobacco and also a group of unexposed matched referents. Data were collected with a self administered questionnaire, flow volume spirometry, measurements of diffusing capacity of the lung for carbon monoxide, chest radiography and skin prick tests. A questionnaire was also sent to former workers of the factory. RESULTS: There were no significant differences between the groups in the prevalence of respiratory symptoms and chest radiography findings. Nine of 102 tobacco workers had pulmonary fibrosis of at least 1/0 (according to the International Labour Organisation (ILO) 1980 classification) and the corresponding figure was five for the referents. The tobacco workers tended to have a low forced vital capacity (FVC), and they had impaired forced expiratory volume in 1 second and lower means of the maximal expiratory flow at 25% of the FVC significantly more often than the referents. Diffusing capacity tended to be lower among the referents. The referents more often had atopy and earlier atopic diseases than the exposed workers. These results indicate the possibility of selection among the exposed workers. CONCLUSIONS: No excess of prevalence of respiratory symptoms in the tobacco workers was found. According to the questionnaire episodes of allergic alveolitis may have occurred in the cigar factory workers. However, in the absence of impairments in lung function and radiological changes it was not possible to distinguish humidifier fever and allergic alveolitis. In exposure conditions that include humidification of the air humidifier, fever and allergic alveolitis constitute a risk for tobacco workers. No effects were shown of exposure to tobacco dust on lung function.

Background Amino alcohols are low molecular weight chemicals used widely in industrial processes, often as minor constituents. They have been found to cause allergic contact dermatitis. Marked exposure through airways is uncommon in other than occupational settings where chemicals containing amino alcohols may be heated or vaporized, liberating free amino alcohols into the ambient air. A few cases of asthma and allergic rhinitis have been reported, but the amounts inducing the airway reactions have not been defined. Objective To further characterize ethanolamine-induced asthma and define the concentration inducing the asthmatic reaction, a case of diethanolamine-induced occupational asthma in a patient handling diethanolamine containing cutting fluid is reported. Methods Suspicion of work related asthma was raised by symptoms and peak expiratory flow monitorings at work and at home. Specific bronchial provocation tests with the cutting fluid containing DEA and with DEA aerosol at two different concentration below the American Conference of Governmental Industrial Hygienists threshold limit value of DEA (2.0 mg/m3) were done. Results DEA caused asthmatic airway obstruction at two different concentrations below the ACGIH TLV. A slight dose–response relationship was observed. Specific IgE-antibodies against DEA could not be found. Conclusions DEA is able to induce occupational asthma by a sensitization mechanism, the exact pathophysiological mechanism of which is not known.

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.

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.

Five mucin populations were isolated from the cardiac region,corpus and antrum of pig gastric mucosa. The released neutral oligosaccharides were permethylated and analysed using high-temperature gas chromatography-mass spectrometry (GC-MS) as well as matrix-assisted laser-desorption mass spectrometry (MALDI-MS). Thirty different oligosaccharides with up to six monosaccharide residues were characterized using both techniques, but the presence of an additional 49 structures was suggested on the basis of their molecular mass by MALDI-MS. Oligosaccharides based on core-1 (Galbeta1-3GalNAcalpha1-) and core-2 [Galbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-] structures were widely distributed, whereas core-3 structures (GlcNAcbeta1-3GalNAcalpha1-) were present only in mucins from the cardiac region and corpus, and core-4 structures [GlcNAcbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-] were present exclusively in mucins from the cardiac region. Furthermore the oligosaccharides from one of the mucins from the corpus were significantly longer than those from the other populations. The results illustrate vast structural diversity, but the relative abundances show only a few dominating structures, suggesting that many oligosaccharides may be quite rare in pig gastric mucins. Well-defined mucin populations with distinctly different glycosylation can thus be identified in pig stomach, suggesting that glycosylation of the large secreted mucins from this tissue is not a random event.

Summary Objective The aim of this study was to compare the IgE response to the most commonly farmed fur animals with that to domestic animals. Methods IgE-immunoblotting and RAST-inhibition analyses were performed using RAST-positive sera from fur workers sensitized to fur allergens and sera from patients sensitized to domestic animal allergens. Results The urine extracts of mink, blue fox, silver fox, racoon dog and fitchew contained more protein bands than the fur extracts did. Allergens with the same molecular weight were found in all of the fur and urine extracts. The most prominent allergenic bands had molecular weights of 62–67 kDa, 23–25 kDa and 18–19 kDa. With crossreacting sera the reciprocal RAST inhibition with all five animal extracts indicated common IgE-binding epitopes, probably common allergens (especially the 62–67 kDa bands). Urine and fur contain common allergens, since urine allergens strongly inhibited the IgE-binding to fur allergens. The IgE binding to allergenic bands of fur animal extracts was also observed in immunoblotting when dog and cat RAST-positive sera were used, but not for cow RAST- positive sera. RAST inhibition of dog-positive sera with fur animal extracts and fur-positive sera with dog extract confirmed the crossreactivity of these IgE antibodies. No such inhibition was seen with cow extract. Conclusion The results of the RAST inhibition and immunoblotting suggest that fur animals have IgE binding epitopes or allergens in common with cat and dog – possibly albumin but not with cow.

OBJECTIVES: To assess the exposure to enzymes and prevalence of enzyme sensitisation in the baking industry. METHODS: A cross sectional study was conducted in four bakeries, one flour mill, and one crispbread factory. Sensitisation to enzymes, flours, and storage mites was examined by skin prick and radioallergosorbent (RAST) tests. 365 workers were tested. The workers were interviewed for work related respiratory and skin symptoms. Total dust concentrations were measured by a gravimetric method, and the concentration of alpha-amylase in air was measured by a catalytic method. An immunochemical method was used for measuring cellulase and xylanase in air. RESULTS: Total measured dust concentrations were from 0.1 to 18 mg/m3, with highest values in dough making areas of bakeries. The alpha-amylase concentrations generally followed the total dust concentrations and reached the highest values < 6.6 micrograms/m3 in the same areas. Cellulase and xylanase varied with concentrations < 180 ng/m3 and < 40 ng/m3, respectively, in the flour mill and the crispbread factory. No cellulase, but concentrations of 1-200 ng/m3 xylanase, were found in the bakeries, probably indicating the natural xylanase activity of wheat. 12 workers (8%) in the bakeries, three (5%) in the flour mill, and four (3%) in the crispbread factory were skin prick positive to enzymes. The corresponding percentages of positive reactions to flours were 12%, 5%, and 8%. CONCLUSIONS: The study confirmed that industrial enzymes in baking used as additives in a powdered form pose a risk of sensitisation. The no effect air concentrations for industrial enzymes are not known. Based on present knowledge, however, lowering exposures and eliminating short and high peaks by technical measures would lower the risk of sensitisation. This would be most effectively accomplished by shifting to non-dusty products.

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 (FEV(1.0)), 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.

Enzymes can cause allergic asthma and rhinitis. Although patients sometimes complain of symptoms in their throat, we have not been able to find any published report of pharyngeal edema caused by exposure to enzymes. We present the case of a maintenance foreman who worked in a factory producing enzymes, and who had pharyngeal edema, asthma, and rhinitis at work. Prick tests for cellulase enzyme and cellulase RAST were positive. The causal association between his pharyngeal symptoms and cellulase was demonstrated with inhalation provocation tests in an exposure chamber.