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.

The production of interferon-alpha(IFN-alpha), IFN-beta, and IFN-gamma by airway leukocytes from induced sputa (IS) of asthmatics was investigated. The groups consisted of 32 corticosteroid-free asthmatics (A), with 13 nonsmokers (nS) and 19 smokers (S), and 30 inhaled corticosteroid-treated asthmatics (cA) with 14 nS and 16 S. The control healthy group (H) comprised 11 nS and 15 S. The levels of IFNs in media from cultures of IS leukocytes were assessed by ELISA. The cells of the smokers produced lower amounts of IFN-alpha than those of nonsmokers in groups H, A, and cA (p = 0.0417, 0.0002, 0.0495, respectively) and significantly higher amounts of IFNbeta than nonsmokers in groups H (p = 0.0044) and cA (p = 0.0007). No differences in the levels of IFN-gamma were observed between S and nS in groups H (p = 0.8148), A (p = 0.8339), and cA (p = 0.0722). In the entire group of smokers, smoking indices correlated negatively with IFN-alpha (R(S) = -0.4374, p = 0.0006), and positively with IFN-beta (R(S) = 0.4239, p = 0.0009). There was no correlation with IFN-gamma (R(S) = 0.0471, p = 0.7004). The results suggest that production of IFNs by the airway leukocytes of cA may be modified by cigarette smoking toward deficient production of IFN-alpha and excess production of IFN-beta, which may have implications in the pathophysiology of asthma.

A b s t r a c tIntroduction: The reversibility test measures an increase in ventilation parameters after the administration of 400 µg of a short-acting β-agonist (SABA). It is worth noting that a typical dosage, applied as a rescue medicine for bronchospastic dyspnoea, is significantly less, i.e., 100-200 µg. Aim: To assess the effects of inhaled 400 µg fenoterol (in the bronchodilator reversibility test) on the heart rate and the development of tachyarrhythmias in subjects aged 65 and above. Material and methods: A total of 53 subjects (45 women) aged 77; 68-82 (median; interquartile range) in stable clinical condition were included in the study. Data including medical history, physical examinations, blood biochemistry, chest X-ray, 12-lead electrocardiogram, 24-hour Holter ECG monitoring, bronchodilator test, and echocardiography were obtained. During the Holter ECG monitoring, the bronchodilator test using 400 µg fenoterol (Berotec pMDI) was performed. Results: A slight but statistically significant (p = 0.02) increase in heart rate from 71 to 75 per min (median) was noted after the administration of fenoterol. No statistically significant differences were found in the number of extrasystolic beats of either supraventricular (p = 0.42) or ventricular origin (p = 0.50). In addition, the subjects did not show any potentially dangerous arrhythmias or significant signs of coronary artery disease. However, there was a significant increase in the number of supraventricular beats in the subjects who were not taking β-blockers. Conclusions: The use of 400 µg fenoterol in a bronchodilator reversibility test in elderly subjects does not entail any significant cardiovascular risk.

Background Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology which affects the whole body. Extensive fibrosis of the skin and internal organs (including lungs – interstitial lung disease (ILD)) are typical for SSc. However the level of NO in exhaled air has been limited diagnostic value. Previous studies suggest that it seems to be a good predictor of the involvement of pulmonary tissue [1,2,3]. Some authors suggest it can be even a marker of early lung involvement in the disease. Objectives To measure the level of NO in exhaled air in a group of patients with SSc and to compare the concentrations of NO with pulmonary function tests and standard parameters assessed in patients with SSc. Methods Seventeen patients were enrolled in the study, of which 13 fulfilled the ACR criteria for SSc. Four patients presented typical symptoms of SSc: Raynaud phenomenon, capillaroscopic pattern, presence of ANA and specific autoantibodies (Scl-70, ACA) and ILD (3 cases), but had no skin changes. The necessary data concerning the disease activity were collected including blood tests, capillaroscopy and modified Rodnan skin score (mRSS). All the patients included in the study, underwent lung function tests (spirometry, diffusion capacity DLCO). The measurements of exhaled NO (FeNO, fraction of exhaled nitric oxide at a flow of 50 ml/s) were done using NIOX analyser (Aerocrine). The diagnosis of pulmonary involvement was based on clinical examination, x-ray pictures of the chest or, if there were indications, on high resolution computer tomography (HRCT). The statistical analysis was performed by using the Statistica 9 software. Results The study involved 17 pts (3 men, 14 women); mean age 52.4±12.37 years; mean disease duration 3.0±2.91 years. The measured concentrations of exhaled NO range from 0.8 to 28.2 ppb (parts per billion). We found correlations of NO neither with pulmonary function tests nor indicators of disease status such as capillaroscopic pattern of nailfold capillaries, ESR, C-reactive protein serum concentration, presence of digital ulcers and the value of mRSS. No statistically significant correlation was found between exhaled NO levels and the presence of ILD. Conclusions The results of this small observational study do not confirm earlier suggestions about the predictive value of NO concentrations in exhaled air. References Tiev KP, Le-Dong NN, Duong-Quy Set al. Exhaled nitric oxide, but not serum nitrite and nitrate, is a marker of interstitial lung disease in systemic sclerosis.Nitric Oxide.2009 May;20(3):200-6. Malerba M, Radaeli A, Ragnoli B et al. Exhaled nitric oxide levels in systemic sclerosis with and without pulmonary involvement.Chest.2007 Aug;132(2):575-80. Tiev KP, Cabane J, Aubourg Fet al. Severity of scleroderma lung disease is related to alveolar concentration of nitric oxide.Eur Respir J.2007 Jul;30(1):26-30. Disclosure of Interest None Declared