Safety of bronchodilator reversibility test in elderly subjects: a prospective study.

INTRODUCTION: The reversibility test measures an increase in ventilation parameters after the administration of 400 mg of a short-acting ß-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 mg. AIM: To assess the effects of inhaled 400 mg 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 mg 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 ß-blockers. CONCLUSIONS: The use of 400 mg fenoterol in a bronchodilator reversibility test in elderly subjects does not entail any significant cardiovascular risk.

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.

Diverse production of interferons alpha, beta, and gamma by airway leukocytes of asthmatics with regard to cigarette smoking and corticosteroid treatment.

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.

[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.

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.