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Anamnestic and immunological data of workers of a platinum refinery (group A: workers with work-related symptoms. n = 8; group B: workers with symptoms not clearly work-related, n = 9; group C: asymptomatic workers. n=13) and controls (group D: atopics, n= 10; group E: non-atopics, n= 16) were compared. Exposure to platinum salt was higher in group A than in groups B or C. In group A. symptoms developed 4 months (median) after the onset of exposure. All subjects of group A and three workers of group B, but none of the workers of the other groups, showed a positive cutaneous reaction to (PtCl6)2-. Total serum IgE was higher in groups A and D than in groups B, C or E. (PtCl6)2- -specific IgE was higher in group A. but there was non-specific binding of (PtCl6)2- to IgE. Histamine release with (PtCl6)2- was found in all groups and was highest in atopic controls. Histamine release with (PtCl6)2- and histamine release with anti-IgE showed an excellent correlation, suggesting a similar release mechanism of (PtCl6)2- and anti-IgE. In skin-test positive subjects. high cutaneous (PtCl6)2--sensitivity is linked to high histamine release with (PtCl6)2- or anti-IgE. supporting the concept of a role of cell surface IgE or IgE-Fc-receptor in the release process with platinum salts. However, high specificity of cutaneous reactions contrasts with low specificity of in-vitro tests with (PtCl6)2-. A different reaction of basophils and mast cells, when challenged with free platinum salts, is hypothesized. We conclude that neither histamine release from basophils with (PtCl6)2- nor RAST for the detection of (PtCl6)2--specific IgE are helpful in the diagnosis of platinum salt allergy. [ABSTRACT FROM AUTHOR]

Focuses on the risk factors and prevention of asthma. Exposure and sensitization to inhalant allergens; Consideration of genetic factors to development of sensitization; Investigation of intervention strategies for prevention.

Background Skin prick testing (SPT) is the basic method for diagnosing IgE-mediated allergies. However, skin reactivity is related to the quality of allergen extracts, which are often poorly defined for occupational allergens. Objective To compare wheat and rye flour SPT solutions from different producers. Materials and methods Standardized SPTs were performed in seven allergy centres with wheat and rye flour solutions from four producers in 125 symptomatic bakers. Optimal cut-off levels for weal sizes were assessed with the Youden Index. Comparisons between SPT results of different solutions were made with flour-specific IgE (sIgE) as the gold standard. Sensitivities, specificities, positive and negative predictive values, and test efficiencies were calculated and compared with McNemar and χ2-tests. The influence of the choice of the gold standard (sIgE or challenge) test was examined for 95 subjects. Additionally, SPT solutions were analysed for protein and antigen content. Results The optimal cut-off level for all SPT solutions was a weal size of ⩾1.5 mm. While differences between wheat and rye flours were small, differences between producers were important. Variability of sensitivities (0.31–0.96), negative predictive values (0.42–0.91), and test efficiencies (0.54–0.90) were higher than variations of specificities (0.74–1.00) and positive predictive values (0.88–1.00). Similar results were obtained when using challenge test results as the gold standard. Variability could be explained by the different antigen contents of the SPT solutions. Conclusion There is a wide variability of SPT solutions for wheat and rye flour from different producers, mainly with respect to sensitivities, negative predictive values, and test efficiencies. Improvement and standardization of SPT solutions used for the diagnosis of baker's asthma are highly recommended. [ABSTRACT FROM AUTHOR]

Background: Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker’s asthma is based on inhalation challenge tests with flours. Aims of the study: To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker’s asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. Methods: Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. Results: Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74–100% (74–100%) for wheat and 82–100% (91–100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. Conclusion: High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers. [ABSTRACT FROM AUTHOR]

It is widely accepted that nonspecific tissue reactivity is a distinct pathophysiological hallmark of allergic diseases, influenced by genetic and environmental factors different from those involved in causing sensitization and allergen response of target organs. This consensus document aims at reviewing procedures currently used for nonspecific provocation of the bronchi, nose and eye and for measuring their responsiveness to nonspecific stimuli. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) and asthma are common complex diseases characterized by airflow obstruction and inflammatory processes in the small airways. lnterleukin 8 (IL-8) is a potent proinflammatory cytokine which interacts with the IL-8 receptora(IL8RA, CXCR1) andß(IL8RB, CXCR2), leading to activation and migration of leukocytes. In order to evaluate the role of the IL8RA gene in the pathogenesis of COPD and asthma, we screened the coding region of IL8RA for mutations by means of single-strand conformation polymorphism analysis in 50 COPD patients and identified three exchanges (M31R, S276T and R335C). These three polymorphisms were subsequently genotyped in 182 adult patients with COPD, 68 adult patients and 130 children with asthma as well as 454 healthy controls. The frequencies of the IL8RA 31R and 335C alleles were significantly increased in patients with COPD and in children with asthma compared to healthy controls (P=0.0073 and 0.023, respectively). Thus, these polymorphisms may play a role in the pathogenesis of COPD and asthma.Genes and Immunity (2005) 6, 225-230. doi:10.1038/sj.gene.6364181 Published online 17 March 2004 [ABSTRACT FROM AUTHOR]

Background and methods: Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR. Results: We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 x 105 viral copies/ml in nasal lavage and 1.88 x 105 viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD. Conclusion: HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are a common cause of hospital admission. Many exacerbations are believed to be due to upper and/or lower respiratory tract viral infections, but the incidence of these infections in patients with COPD is still undetermined.Methods: Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3, and picornaviruses were detected by nested reverse transcription polymerase chain reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE-COPD and 42 patients with stable COPD admitted for other medical reasons were studied.Results: Respiratory viruses were found more often in sputum and nasal lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD (8/42, 19%, p<0.01). The most common viruses were picornaviruses (21/59, 36%), influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed separately, this difference was seen in induced sputum (exacerbation 40/85 (47%) v stable 4/42 (10%), p<0.01) but was not significant in nasal lavage (exacerbation 26/85 (31%) v stable 7/42 (17%), p=0.14). In patients with AE-COPD, fever was more frequent in those in whom viruses were detected (12/48, 25%) than in those in whom viruses were not detected (2/37, 5%, p=0.03).Conclusion: Viral respiratory pathogens are found more often in respiratory specimens of hospitalised patients with AE-COPD than in control patients. Induced sputum detects respiratory viruses more frequently than nasal lavage in these patients. These data indicate that nasal lavage probably has no additional diagnostic value to induced sputum in cross-sectional studies on hospitalised patients with AE-COPD and that the role of viral infection in these patients is still underestimated. [ABSTRACT FROM AUTHOR]

Discusses factors responsible for the underdiagnosis of obstructive sleep-apnea-hypopnea-syndrome (OSAHS) in women. Gender-specific differences influencing the diagnosis of OSAHS; Reason for a delayed diagnosis of the disease.

Examines whether human bronchoepithelial cells respond to rockwool fibers by induction of manganese superoxide dismutase (MnSOD) messenger RNA (mRNA) and an increase of MnSOD activity levels. Selective induction of MnSOD mRNA and elevation of MnSOD protein in pulmonary epithelial cells exposed to crocidolite asbestos or critobalite silica; Use of scanning electron microscopy to confirm close dust cell contact.

This study quantifies the antioxidant function of ambroxol (2-amino-3,5- dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine) in vitro. Polymorphonuclear cells (PMN) and mononuclear cells were isolated from the blood of healthy volunteers (n = 46) to determine reactive oxygen species (ROS) by luminol-enhanced chemiluminescence. Ambroxol or the controls N-acetylcysteine (NAC), nacystelyn (NAL), glutathione (GSH), superoxide dismutase (SOD), catalase, and the combination of SOD/catalase were incubated for 1 or 2 h with zymosan-activated cells in vitro using concentrations ranging from 10&sup-6; to 10&sup-3; mol/liter. Reduction of ROS-mediated luminescence was similar within the cell types. Ambroxol (10&sup-4; mol/liter) reduced ROS about 75% (1-h incubation) and 98% (2-h incubation), respectively (p < 0.001). SOD and SOD/catalase, but not the H[sub2]O[sub2] -catalyzing substances (NAC, NAL, GSH, and catalase), reduced cellular ROS. This indicates that inflammatory cells predominantly generate O-[sub2], which can be scavenged by ambroxol. The antioxidant function of ambroxol with increasing incubation time suggests additional cellular antiinflammatory properties of this substance. Our results indicate that good antioxidant function of ambroxol is related mainly to direct scavenger function of reactive oxygen metabolites such as O-[sub2] . However, an antioxidative effect of ambroxol may also be associated with the reduction of prooxidative metabolism in inflammatory cells. Concluding from this observation, and because of the well known high affinity of ambroxol for lung tissue, ambroxol may be an alternative in antioxidant augmentation therapy, particularly in pulmonary diseases characterized by an overburden of toxic oxygen metabolites. [ABSTRACT FROM AUTHOR]