The G/G genotype of transforming growth factor beta 1 (TGF-beta1) single nucleotide (+915G/C) polymorphism coincident with other host and environmental factors is associated with irreversible bronchoconstriction in asthmatics.

Irreversible airflow obstruction may develop in some cases of asthma even in absence of known risk factors such as smoking and environmental insults and despite implementing apparently appropriate therapy. This implies that genetic factors may significantly contribute to determining the severity in the course of the disease. The published reports on genetic predisposition to irreversible bronchoconstriction in asthma, however, are relatively scarce, and disregard its potential association with transforming growth factor (TGF)-beta1 gene polymorphism despite established role that TGF-beta1 plays in airway remodelling. We tested TGF-beta1 single-nucleotide polymorphisms (SNPs) at position +869 of codon 10 (leucine or proline) and position +915 of codon 25 (arginine or proline) for association with irreversible bronchoconstriction in a case-control study involving 110 patients with asthma and 109 controls. Multivariate logistic regression analysis revealed that genotype G/G at codon 25 was significantly associated with irreversible bronchoconstriction in asthmatics (odds ratio = 4.44; 95% confidence interval: 1.00-19.61; P = 0.05), but only after adjustment for gender, disease duration and smoking index. The influence of SNPs at codon 10 on irreversible airway obstruction was not significant. Our results suggest that presence of SNP (+915G/G) at codon 25 in TGF-beta1 gene may predispose to the development of irreversible bronchoconstriction in asthmatic patients, but only when coincident with the male gender, habitual smoking and relevant duration of the disease.

Serum concentration of C-reactive protein is not a good marker of bronchial hyperresponsiveness.

INTRODUCTION: Asthmatic inflammation is responsible for vital features of the disease, including bronchial hyperresponsiveness (BHR). At present we do not have precise markers for monitoring asthmatic inflammation. C-reactive protein (CRP), a marker of systemic inflammation, seemed to be a factor which could also reflect the level of asthmatic inflammation expressed by BHR. Therefore the relationship between CRP concentration and BHR was evaluated. MATERIALS AND METHODS: One hundred and two patients entered the study. A skin prick test with a broad spectrum of common aeroallergens as well as baseline spirometry and a histamine bronchoprovocation test were performed in each subject. Blood samples for high-sensitivity CRP (hsCRP) measurement were taken before the bronchial challenge tests. RESULTS: Serum hsCRP concentrations ranged from 0.20 to 14.5 mg/l (median: 1.2 mg/l, 25-75% quartiles: 0.6-2.4). Positive skin prick tests were found in 26 subjects. Bronchial hyperresponsiveness was confirmed in 42 patients (first subgroup), while 60 subjects did not demonstrate BHR (second subgroup). Among the patients with BHR, asthma was diagnosed in 33 cases and Corrao syndrome in 9. In both subgroups, serum hsCRP concentrations had similar levels (median: 1.4 mg/l, 25-75% quartiles: 0.8-2.4 and median: 0.9 mg/l, 25-75% quartiles: 0.5-2.8, respectively; p=0.297). There was no statistically significant correlation (r = -0.163, p = 0.302) between serum hsCRP concentration and the level of BHR expressed as the 20% provocative concentration for histamine. In addition, hsCRP serum concentration, after adjustment for age, atopy, body mass index, and gender, was not a significant predictor of positive histamine bronchoprovocation test results (p = 0.22, CONCLUSIONS: Serum hsCRP concentration is not a good marker of BHR, which is mainly dependent on asthmatic inflammation and is measured during bronchial challenge with histamine. This finding is important for interpreting and discussing results obtained from epidemiological and population-based studies on relationships between either CRP concentration and BHR or local and systemic inflammation.

Corticosteroid-induced laryngeal disorders in asthma.

BACKGROUND: Inhaled corticosteroids have proven to be the most effective agent available in treating bronchial asthma, and such treatment is believed to be very safe. Concerns regarding side effects of inhaled corticosteroids usually focus on potential systemic effects, where local side effects are often overlooked. The purpose of this study was to analyze and assess the influence of inhaled corticosteroids on the vocal cords of patients treated for bronchial asthma. MATERIAL/METHODS: Fifty patients (mean age: 50 years, range: 22 to 83 years) suffering from asthma and receiving corticosteroidal inhaled agents entered in this study. All of the patients underwent detailed videoscopic examination of the larynx. None complained of any laryngeal disorders or dysfunction before the diagnosis of asthma. All of the patients were non-smokers. RESULTS: Significant changes in the laryngeal status were observed. Changes included atrophy of laryngeal mucosa, vocal fold atrophy, and vocal fold bowing. CONCLUSIONS: Damage to the larynx is an important factor in patients with asthma treated with inhaled corticosteroids, which elicit apoptosis of the epithelium.

The overproduction of nitric oxide associated with neutrophilic predominance is relevant to airway mycotic infections in asthmatics undergoing prolonged glucocorticoid treatment.

The complex relationship between the local inflammatory response and the spread of airway mycosis during prolonged glucocorticoid therapy in bronchial asthma patients remains unclear. We assessed the ability of airway leukocytes to produce nitric oxide (NO) in relation to differential inflammatory cell counts, levels of asthma severity, and coexisting airway mycotic infections. The study was carried out on leukocytes from the induced sputa (IS) of 14 patients with asthma complicated by mycotic airway infections undergoing prolonged glucocorticoid therapy (group FcA). Three groups of subjects without airway fungal infections were also studied: 18 glucocorticoid-treated asthmatics (group cA), 11 steroid-free asthmatics (group A), and 13 healthy control subjects (group H). In group FcA, both the level of spontaneous production of NO and the percentages of neutrophils in the IS were significantly higher than in all the remaining groups. Additionally, a significant positive correlation was noticed between the NO levels and both the percentages of neutrophils in the IS and the symptom intensity scores. The results suggest a possible predominant role of neutrophils in the overproduction of NO related to asthma severity and coexisting fungal infections in glucocorticoid-treated patients.

[Markers of oxidative balance and concentration of selected metals in pollinotics]. / Markery równowagi oksydacyjnej i stezenia wybranych metali u osób chorych na pylkowice.

It was reported that catalytically active metals are presented in both the soluble and insoluble fractions of ambient air pollution particles. Both catalyses generate and stimulate oxidative stress. There are very few reports on the role of oxidative stress in pollen allergy Theoretical presumptions may suggest that oxidative metabolism can be influenced by the activity of some metals and, on the other hand, pollens could be a carrier of at least catalytic amount of metals. The aim of our study was to evaluate concentrations of some metals (Cd, Cr, Pb, Ni, Mg, Zn) and compare the markers of oxidative balance expressed as malondialde-hyde (MDA) concentration, superoxide dismutase (SOD) and glutathion peroxidase (GPx) activities in the blood of patients with pollinosis. The investigation was performed on the group of 50 individuals, 34 diagnosed as pollen allergic and 16 healthy volunteers. We have found Pb blood concentration higher in pollen allergics group, but only on the verge of statistical significance (p = 0.058). No statistically significant differences in the concentrations of other examined metals between pollen allergics and controls were observed; whereas SOD activity was higher in allergics (p = 0.015), GPx activity lower in allergics (p = 0.045) and MDA concentration higher in allergics (p = 0.044). The positive linear correlations between SOD and Pb (r = 0.492; p < 0.001) as well as between Mg and MDA (r = 0.329; p = 0.02) were observed. On the basis of these results we formulated the following hypotheses, in our opinion worth further investigations: The statistically significant increase in SOD activity in the group of pollen allergics when compared to the group of controls points out the role of oxidative stress in pollen allergic persons. The statistically significant decrease in GPx activity suggests the long-lasting duration of oxidative stress in pollen allergic. The positive correlation between SOD activity and Pb level may suggest the putative role of Pb in oxidative stress. The positive correlation between Mg and MDA may suggest the presence of an additional mechanism in pollen allergy probably connected with the activation of phagocytosis by magnesium.

[TGF-beta1 gene polymorphism in chronic obstructive pulmonary disease]. / Polimorfizm genu TGF-beta1 w przewleklej obturacyjnej chorobie pluc.

Gene polymorphism is often responsible for occurrence of some chronic diseases. It has not been clarified, why only 15-20% of smokers suffer from chronic obstructive pulmonary disease (COPD). TGF-beta1 gene polymorphism has been postulated as one of possible genetic risk factors. The aim of our study was to evaluate TGF-beta1 gene polymorphism in codons 10 and 25 in COPD patients in comparison to healthy controls. Thirty six COPD patients and 60 healthy persons entered the study. The distribution of TGF-beta1 genotypes in codon 10 was as follows in COPD group: T/C--50%, T/T--25% and C/C--25% in control group: 45%, 42% and 13% respectively. The distribution of genotypes in codon 25 in COPD patients was: G/G 86% and G/C 14%, in control group 83% and 17% respectively. There were not statistically significant differences between evaluated groups with regard to both polymorphisms. Moreover, in group of 27 smokers without COPD the distribution of the analysed TGF-beta1 gene polymorphism was similar to that in COPD group. After adjustment to sex, age and smoking index, in the logistic regression model, we can not confirm the hypothesis that TGF-beta1 gene polymorphisms in codons 10 and 25 might be significant risk factors of COPD.

Prevalence of Hymenoptera venom allergy and its immunological markers current in adults in Poland.

BACKGROUND: The prevalence of insect venom allergy is still being assessed. The aim of our study was to estimate, on the basis of an interviewer-administered questionnaire survey, the frequency of post-sting allergic reactions and venom sensitization. MATERIAL/METHODS: The study was performed within the framework of the ECRHS. A random sampling of 3000 persons was selected from among 68,000 persons living in the area of Wroclaw, Poland. Of the 2050 persons responding to a mailed screening questionnaire, 169 were randomly selected to complete a questionnaire designed only for insect allergy detection. Venom skin test and sIgE assessment were performed on 146 and 132 patients, respectively. RESULTS: Allergic post-sting symptoms were found in 20.7% of surveyed patients. Large local reactions (LLs) occurred in 11.8% and systemic reactions (SYSs) in 8.9% of the study population. SYS was most often manifested by urticaria (4.7%). The frequencies of SYS II, III and IV were 1.8%, 1.8%, and 0.6%, respectively. Only LLs were more frequent in subjects with other allergic diseases (p=0.03). The presence of positive skin tests and/or sIgE in serum were 42.8% of subjects with LL, 53.3% with SYS, and 17.1% of "asymptomatic" patients. No significant differences were found between these groups regarding venom skin test results and sIgE serum concentrations. Occurrence of sIgE to bee venom was frequently associated with the presence of sIgE to timothy grass. CONCLUSIONS: Insect venom allergy and asymptomatic venom sensitization in adults are common in Poland. Only some venom allergy cases are IgE dependent.

Comparison of leukocyte populations from bronchoalveolar lavage and induced sputum in the evaluation of cellular composition and nitric oxide production in patients with bronchial asthma.

Bronchoalveolar lavage (BAL) or induced sputum (IS) techniques may provide leukocytes for the evaluation of airway inflammatory response in bronchial asthma. The aim of the present study was to compare features of leukocyte populations obtained by the two different methods regarding the cell types and their activity in patients with bronchial asthma. The nitric oxide (NO) level released from the cells was measured as a marker of their activity. Pulmonary leukocytes were obtained from the BAL and IS of 11 asthmatic patients in stable condition at the time of the study. The BAL and IS leukocyte populations varied in cell count and NO production. Macrophages were the predominant leukocyte population in BAL (median (Me) = 83.0%, range 67.9-88.4%), whereas sputum sediments were found to consist mainly of neutrophils (Me = 55.7%, range 29.0-64.9%). The IS leukocytes released much more NO (p = 0.0022) than the BAL leukocytes. In spite of these quantitative differences, a similar pattern of NO production was observed in BAL and in IS cells. Both BAL and IS leukocyte populations produced almost the same amounts of NO before and after lipopolysaccharide stimulation (p = 0.9063, p = 0.4801, respectively). Furthermore, a slight positive correlation Spearman's rank (RS) = 0.5578, p = 0.0594) was noticed between the neutrophil percentages and NO levels produced by BAL cells, whereas in IS a statistically significant correlation between the percentage of neutrophils and the levels of NO (RS = 0.6643, p = 0.0184) was observed. In conclusion, the BAL and IS leukocyte populations are different in cell type, their size and activity. Depending on the asthma severity and the type of cells needed in a study, either BAL or IS specimens may be chosen as a source of pulmonary leukocytes. The use of IS as a noninvasive technique is supposed to be potential value particularly in the study of the airway inflammatory response mediated mainly by neutrophils, i.e. during and/or after exacerbation of the disease. Based on our results, a possible contribution of neutrophils in the production of NO in the airways of asthmatic patients can be proposed apart from other cells such as macrophages.