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.

Occupational asthma due to manual metal-arc welding of special stainless steels.

Occupational asthma (OA) can be induced by fumes of manual metal-arc welding on stainless steel. In recent years, the use of special stainless steels (SSS) with high chromium content has increased. This study presents two cases of OA caused by manual metal-arc welding on SSS. In both cases, the diagnosis of OA was based on respiratory symptoms, occupational exposure and positive findings in the specific challenge tests. In the first case, a 46-yr-old welder had experienced severe dyspnoea while welding SSS (SMO steel), but not in other situations. Challenge tests with both mild steel and stainless steel using a common electrode were negative. Welding SSS with a special electrode caused a delayed 37% drop in forced expiratory volume in one second (FEV1). In the second case, a 34-yr-old male had started to experience dyspnoea during the past few years, while welding especially SSS (Duplex steel). The workplace peak expiratory flow monitoring was suggestive of OA. Challenge tests with both mild steel and stainless steel using a common electrode did not cause bronchial obstruction. Welding SSS with a special electrode caused a delayed 31% drop in FEV1. In conclusion, exposure to manual metal-arc welding fumes of special stainless steel should be considered as a new cause of occupational asthma.

Agents causing occupational asthma in Finland in 1986-2002: cow epithelium bypassed by moulds from moisture-damaged buildings.

BACKGROUND: Occupational asthma is an avoidable form of asthma. In Finland, the diagnosis of occupational asthma entitles substantial compensation to the employee. The diagnostics are based on symptoms, exposure assessment, allergologic investigations, follow-up of peak expiratory flow (PEF) at work and at home and, in many cases, specific challenge tests. OBJECTIVE: To study the causative agents of occupational asthma in Finland. METHODS: The causative agents and the numbers of new occupational asthma cases notified to the Finnish Register of Occupational Diseases (FROD) during 1986-2002 are reported. RESULTS: The number of occupational asthma cases increased from 1986 until 1995, after which a downward trend, stabilizing during the last few years, has been observed. The majority of the cases (59%) in the beginning of the period (1986-1990) were associated with agriculture, but the percentage has fallen thereafter (42% of the cases in 1998-2002) along with the fall in the total number of cases. Since 1995, indoor moulds from water-damaged buildings have caused an increasing number of cases and have become the most important causative agents (0.5% cases, in 1986-1990 and 18% of the cases in 1998-2002). Chemicals have caused 10-30% of the cases, a decreasing number since 1990. The most important chemicals causing occupational asthma have been diisocyanates and welding fumes, followed by hairdressing chemicals and formaldehyde. CONCLUSIONS: The number of occupational asthma cases in Finland reached its height in the mid-1990s. The decrease in the number of total cases is because of the decrease in agriculture-associated cases, reflecting the number of employees in agriculture-associated occupations, which has greatly decreased since Finland joined the EU in 1995. An epidemic of mould-induced asthma, affecting mostly white-collar employees working in moisture-damaged buildings, has taken place since 1995.

Smoking and asthma in adults.

Studies on the effect of smoking on adulthood asthma have provided contradictory results. The current authors conducted a population-based incident case-control study to assess the effects of current and past smoking on the development of asthma in adults. During a 2.5 yr study period, all new asthma cases clinically diagnosed (n=521) and randomly selected controls (n=932) from a geographically defined district in southern Finland were recruited. The risk of developing asthma was significantly higher among current smokers with an adjusted odds ratio (OR) of 1.33 (95% confidence interval 1.00-1.77) and among ex-smokers with an adjusted OR 1.49 (1.12-1.97) compared with never-smokers. Among current smokers, the risk increased up to 14 cigarettes x day(-1), and a similar trend was observed in relation to cumulative smoking. In conclusion, the current results support the hypothesis that smoking causes asthma in adulthood.

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.

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.

Expression of CYP1A1, CYP1B1 and CYP3A, and polycyclic aromatic hydrocarbon-DNA adduct formation in bronchoalveolar macrophages of smokers and non-smokers.

Variability in the expression of enzymes metabolizing carcinogens derived from cigarette smoke may contribute to individual susceptibility to pulmonary carcinogenesis. This study was designed to determine the effects of smoking and 3 major cytochrome P450 (CYP) enzymes, i.e., CYP1A1, CYP1B1 and CYP3A, which metabolize polycyclic aromatic hydrocarbons (PAH) on PAH-DNA adduct formation in the bronchoalveolar macrophages (BAM) of 31 smokers and 16 non-smokers. CYP protein levels were determined by immunoblotting and PAH-DNA adduct levels by the nuclease P1 enhanced (32)P-postlabeling method. The expression of specific CYP forms was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) from 10 additional samples. CYP3A protein, CYP3A5 by RT-PCR, was detected in the majority of samples from smokers and non-smokers. The levels of CYP3A appeared to be lower in active smokers than in ex-smokers (p = 0.10) or never smokers (p = 0.02). CYP1A1 was not detectable by either immunoblotting or RT-PCR. The expression of CYP1B1 was low or undetectable in most samples. The PAH-DNA adduct levels were higher (mean 1.57/10(8) nucleotides) in samples from smokers compared with non-smokers (mean 0.42/10(8) nucleotides, p < 0.001) and the number of adducts correlated with the number of cigarettes smoked daily (regression analysis, p < 0. 001). Higher levels of adducts were detected in samples from smokers with a high level of CYP3A compared with those with a low level (regression analysis, p = 0.002). As CYP3A5 is abundant in both lung epithelial cells and BAM, its association with adduct formation suggests that this CYP form may be important in the activation of cigarette smoke procarcinogens.

Expression of xenobiotic-metabolizing CYPs in human pulmonary tissue.

The pattern of expression of individual cytochrome P450 (CYP) forms participating in the metabolism of xenobiotics is being increasingly well characterised in the human pulmonary tissue. Recent studies using methods having increased sensitivity and specificity, such as the reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, have revealed constitutive and inducible expression of several CYP forms in different cell types of the human lung. These studies have revealed the presence of mRNA of several procarcinogen-activating CYP forms in whole lung tissue and alveolar macrophages, including CYP1A1, CYP2B6/7, CYP2E1, and CYP3A5. The results of several studies on CYP2D6 expression have yielded contradictory results. Immunohistochemical analysis shows that CYP3A5 protein is present in all lung samples studied, and is localized in the ciliated and mucous cells of the bronchial wall, bronchial glands, bronchiolar ciliated and terminal cuboidal epithelium, type I and type II alveolar epithelium, vascular and capillary endothelium, and alveolar macrophages. Also CYP3A4 protein is found in some cell types in a minority (about 20%) of lung samples. Primary cultures of freshly isolated broncho-alveolar macrophages as well as a continuously growing bronchial carcinoma cell line (A-549) are being used for CYP induction studies in our laboratory. The results indicate that CYP1 family members are inducible in these cells by polycyclic aromatic hydrocarbon (PAH) inducers, and that CYP3A5, but not CYP3A4, is present constitutively. The results of these studies indicate that several different xenobiotic-metabolizing CYPs are present in the human lung and lung-derived cell lines, possibly contributing to in situ activation of pulmonary procarcinogens. Interindividual differences in the expression of these CYPs may contribute to the risk of developing lung cancer and possibly other pulmonary diseases initiated by agents that require metabolic activation.

Diethanolamine-induced occupational asthma, a case report.

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.

Detection of mRNA encoding xenobiotic-metabolizing cytochrome P450s in human bronchoalveolar macrophages and peripheral blood lymphocytes.

Human pulmonary tissue are known to contain enzymes mediating procarcinogen activation. Peripheral blood lymphocytes and bronchoalveolar macrophages (BAMs) have been used as surrogates for the lung in studies involving cytochrome P450 (CYP) parameters, including CYP1A1 inducibility in relation to susceptibility to lung cancer. In this study, a comprehensive view of the expression patterns of xenobiotic-metabolizing CYP forms in human BAMs and peripheral blood lymphocytes was obtained by using gene-specific reverse transcriptase-polymerase chain reaction analysis. These patterns were compared with that in the whole lung. mRNAs of CYP2B6/7, CYP2C, CYP2E1, CYP2F1, CYP3A5, and CYP4B1 were detected in all seven BAM samples studied; however, only the mRNA of CYP2E1 was found consistently in all eight lymphocyte samples. The amounts of amplification products of CYP2B6/7, CYP2C, CYP3A5, and CYP4B1 were low and inconsistent, indicating low levels of expression in lymphocytes. Consistent with previous knowledge, mRNAs of CYP1A1, CYP2B6/7, CYP2E1, CYP2F1, CYP3A5, and CYP4B1 were detected in whole-lung tissue. These results give an overall picture of the expression of CYP genes in the xenobiotic-metabolizing families CYP1, CYP2, and CYP3 in BAMs, peripheral blood lymphocytes, and whole-lung tissue and will aid in directing future studies on the respective protein products. The differences in the CYP gene expression patterns between lung and lymphocytes cast additional doubt on the use of lymphocytes as a surrogate for the lung.

Asbestos bodies in bronchoalveolar lavage in relation to asbestos bodies and asbestos fibres in lung parenchyma.

In Finland, unlike other countries, anthophyllite asbestos has been widely used due to its domestic production in 1918-1975. In this particular context, the aim of the present study was to analyse the relationship between asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid and the concentration of ABs and the different amphibole asbestos fibres in lung tissue. Sixty five BAL lung tissue sample pairs from patients with pulmonary disease were analysed. The concentration of ABs in BAL fluid and lung tissue was determined with optical microscopy, and the concentration, type and dimensions of asbestos fibres in lung tissue with scanning electron microscopy. There was a significant correlation between the concentrations of ABs in BAL fluid and in lung tissue (r = 0.72; p < 0.001), between the concentrations of ABs and amphibole asbestos fibres in lung tissue (r = 0.73; p < 0.001), and between the concentration of ABs in BAL fluid and the concentration of amphibole asbestos fibres in lung tissue (r = 0.64; p < 0.001). In patients who had been exposed mainly to commercial anthophyllite, significantly higher concentrations of ABs were observed per total pulmonary amphibole fibre burden, as compared to patients whose main exposure was to crocidolite/amosite. The anthophyllite fibres in lung tissue were longer than the crocidolite/amosite fibres. The relationship between asbestos body counts in lung tissue and in bronchoalveolar lavage fluid was similar to previous international observations. When using the asbestos body count to predict the underlying total pulmonary amphibole asbestos burden in Finnish patients, however, it should be borne in mind that the relationship between the two parameters seems to be different with anthophyllite as compared to crocidolite/amosite fibres.