Jerzy Liebhart

The G/G genotype of transforming growth factor beta 1 (TGF-β1) 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)‐β1 gene polymorphism despite established role that TGF‐β1 plays in airway remodelling. We tested TGF‐β1 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‐β1 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, OR=0.86, 95% CI).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.

Transforming growth factor-beta in the pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a highly prevalent airway disorder. However, the mechanisms of the pathogenesis of COPD have not been completely elucidated to date. Transforming growth factor (TGF)-β is a pleiotropic, multifunctional cytokine participating in cell differentiation, apoptosis, survival and proliferation. TGF-β is involved in many diseases, including carcinogenesis and fibrosis. Although the most important risk factor for COPD is cigarette smoking, only 10–15% of all smokers develop the disease. This finding raises suspicion that some host or genetic factors may be involved in the pathogenesis of the disease. Thus, special attention has recently been focused on the role in COPD of TGF-β, which is active in inflammation of the airways and particularly in lung remodeling. TGF-β induces chemotaxis of mast cells and macrophages, regulates cell apoptosis and influences the protease/antiprotease balance inhibiting matrix metalloproteinase-9. TGF-β is heavily involved in repair proc...

NMF in Screening Some Spirometric Data, an Insight into 12-Dimensional Data Space

We present the usage of the Non-negative Matrix Factorization (NMF), an unsupervised machine learning method, which learns normal and abnormal state of patient’s ventilatory systems. This is done using samples of patients having defects of obturative and restrictive kind and a control group.