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Background: Long-acting β2-adrenoceptor agonists have been shown to increase the risk of atrial arrhythmias in patients with stable chronic obstructive pulmonary disease. The aim of this study was to investigate whether perioperative long-acting β2-adrenoceptor agonists treatment would increase the risk of postoperative atrial arrhythmias after lung cancer surgery in chronic obstructive pulmonary disease patients.Methods: We retrospectively analyzed 174 consecutive chronic obstructive pulmonary disease patients with non-small-cell lung cancer who underwent lobectomy or segmentectomy. The subjects were divided into those with or without perioperative long-acting β2-adrenoceptor agonists treatment. Postoperative cardiopulmonary complications were compared between the two groups.Results: There were no statistically significant differences between the perioperative long-acting β2-adrenoceptor agonists treatment group and the control group in the incidence of postoperative atrial arrhythmias (P = 0.629). In 134 propensity-score-matched pairs, including variables such as age, gender, comorbidities, smoking history, operation procedure, lung-cancer staging, and respiratory function, there were no significant differences between the two groups in the incidence of postoperative cardiopulmonary complications, including atrial arrhythmias.Conclusions: Perioperative administration of long-acting β2-adrenoceptor agonists might not increase the incidence of postoperative atrial arrhythmias after surgical resection for non-small-cell lung cancer in chronic obstructive pulmonary disease patients. [ABSTRACT FROM AUTHOR]

Background Bacteria and viruses are major causes of chronic obstructive pulmonary disease ( COPD) exacerbations. Molecular components of these pathogens are recognized by pattern-recognition receptors ( PRRs) expressed by various cells in the airway, which leads to initiation of inflammatory processes. Expression levels of PRRs in airway inflammatory cells are expected to affect susceptibility to COPD exacerbation. Aims This prospective observational study was conducted to detect any association between exacerbation and PRR expression. Methods Thirty-one male COPD patients were recruited. At baseline, clinical history, lung function measurements, peripheral blood samples and induced sputum were obtained. Using sputum samples, we performed gene expression analysis of TLR2, TLR3, TLR4, NOD1, NOD2, RIG - I and MDA-5 by quantitative reverse transcription-polymerase chain reaction in addition to quantitative bacterial culture. COPD exacerbations were assessed based on Anthonisen's criteria using symptom diaries for the following 1-year period. Results During 1-year follow-up period, 13 patients experienced at least one exacerbation, but 18 patients did not. Those with exacerbations tended to be more severe COPD and showed larger neutrophil fraction in their induced sputum. Among PRRs, only TLR3 gene expression was increased in COPD patients with exacerbation compared with those without exacerbations. Multivariate logistic regression analysis including neutrophil fraction and TLR3 gene expression as predictor variables demonstrated that only an increase of neutrophil fraction, but not TLR3 gene expression, was a significant predictor for COPD exacerbation. Conclusion TLR3 expression in inflammatory cells might affect the susceptibility to COPD exacerbation. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and persistent inflammation in the airways and lung parenchyma. Oxidative stress contributes to the pathogenesis of COPD. Interleukin (IL)-32 expression has been reported to increase in the lung tissue of patients with COPD. Here, we show that IFNg upregulated IL-32 expression and that oxidative stress augmented IFNg-induced-IL-32 expression in airway epithelial cells. We further investigated transcriptional regulation responsible for IFNg induced IL-32 expression in human airway epithelial cells. Methods: Human bronchial epithelial (HBE) cells were stimulated with H2O2 and IFNg, and IL-32 expression was evaluated. The cell viability was confirmed by MTT assay. The intracellular signaling pathways regulating IL-32 expression were investigated by examining the regulatory effects of MAPK inhibitors and JAK inhibitor after treatment with H2O2 and IFNg, and by using a ChIP assay to identify transcription factors (i.e. c-Jun, CREB) binding to the IL-32 promoter. Promoter activity assays were conducted after mutations were introduced into binding sites of c-Jun and CREB in the IL-32 promoter. IL-32 expression was also examined in HBE cells in which the expression of either c-Jun or CREB was knocked out by siRNA of indicated transcription factors. Results: There were no significant differences of cell viability among groups. After stimulation with H2O2 or IFNg for 48 hours, IL-32 expression in HBE cells was increased by IFNγ and synergistically upregulated by the addition of H2O2. The H2O2 augmented IFNg induced IL-32 mRNA expression was suppressed by a JNK inhibitor, but not by MEK inhibitor, p38 inhibitor, and JAK inhibitor I. Significant binding of c-Jun and CREB to the IL-32 promoter was observed in the IFNg + H2O2 stimulated HBE cells. Introducing mutations into the c-Jun/CREB binding sites in the IL-32 promoter prominently suppressed its transcriptional activity. Further, knocking down CREB expression by siRNA resulted in significant suppression of IL-32 induction by IFNg and H2O2 in HBE cells. Conclusion: IL-32 expression in airway epithelium may be augmented by inflammation and oxidative stress, which may occur in COPD acute exacerbation. c-Jun and CREB are key transcriptional factors in IFNg and H2O2 induced IL-32 expression. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Genetic background is thought to be one of the risk factors for development of COPD. Recently, it has been proposed that the innate immune system is involved in the pathophysiology of COPD. We hypothesized that polymorphisms in the nucleotide-binding and oligomerization domain (NOD)1 and NOD2 genes would be associated with the pathogenesis of COPD. In addition, the associations between these single nucleotide polymorphisms (SNPs) and phenotypes of COPD were analysed. Methods: Japanese COPD patients ( n = 228) and non-COPD smokers ( n = 101) were recruited from the outpatient clinic at Kyoto University Hospital, Kyoto, Japan. At entry into the study, a blood sample was taken and a pulmonary function test was performed. Genotyping was performed for 6 selected tag SNPs of NOD1 and 5 tag SNPs of NOD2. Further investigations were performed for SNP that were associated with COPD, including baseline gene expression, the relative proportions of splicing variants in whole blood, responses to ligand and enhancement of gene expression in peripheral blood neutrophils stimulated with pro-inflammatory cytokines. Results: The distribution of NOD2 rs1077861 genotypes differed between Japanese COPD patients and non-COPD smokers ( P = 0.036). This SNP was also associated with a lower FEV1 % predicted (57.2 ± 1.8 for TT vs 50.8 ± 2.3 for TA/AA, P = 0.03) and DLCO/VA (2.89 ± 0.1 in TT vs 2.53 ± 0.14 in TA/AA, P = 0.036) in COPD patients. NOD2 gene expression after stimulation with 10 ng/mL of tumour necrosis factor-α for 4 h, was increased to a greater extent in TA/AA genotype than in TT genotype peripheral blood neutrophils ( P = 0.015). Conclusions: The NOD2 rs1077861 SNP may influence the development and progression of COPD in Japanese subjects. [ABSTRACT FROM AUTHOR]

Background: Health status, dyspnea and psychological status are important clinical outcomes in chronic obstructive pulmonary disease (COPD). However, forced expiratory volume in one second (FEV1) measured by spirometry, the standard measurement of airflow limitation, has only a weak relationship with these outcomes in COPD. Recently, in addition to spirometry, impulse oscillometry (IOS) measuring lung resistance (R) and reactance (X) is increasingly being used to assess pulmonary functional impairment. Methods: We aimed to identify relationships between IOS measurements and patient-reported outcomes in 65 outpatients with stable COPD. We performed pulmonary function testing, IOS, high-resolution computed tomography (CT), and assessment of health status using the St. George's Respiratory Questionnaire (SGRQ), dyspnea using the Medical Research Council (MRC) scale and psychological status using the Hospital Anxiety and Depression Scale (HADS). We then investigated the relationships between these parameters. For the IOS measurements, we used lung resistance at 5 and 20 Hz (R5 and R20, respectively) and reactance at 5 Hz (X5). Because R5 and R20 are regarded as reflecting total and proximal airway resistance, respectively, the fall in resistance from R5 to R20 (R5-R20) was used as a surrogate for the resistance of peripheral airways. X5 was also considered to represent peripheral airway abnormalities. Results: R5-R20 and X5 were significantly correlated with the SGRQ and the MRC. These correlation coefficients were greater than when using other objective measurements of pulmonary function, R20 on the IOS and CT instead of R5-R20 and X5. Multiple regression analyses showed that R5-R20 or X5 most significantly accounted for the SGRQ and MRC scores. Conclusions: IOS measurements, especially indices of peripheral airway function, are significantly correlated with health status and dyspnea in patients with COPD. Therefore, in addition to its simplicity and non-invasiveness, IOS may be a useful clinical tool not only for detecting pulmonary functional impairment, but also to some extent at least estimating the patient's quality of daily life and well-being. [ABSTRACT FROM AUTHOR]

Background and objective: The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations. Methods: The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C5). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period. Results: The study group comprised 45 COPD subjects and 10 controls. Mean log C5 was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76–1.18) versus 1.26 (95% CI: 0.81–1.71), P = 0.095). In the COPD group, log C5 was negatively correlated with serum CRP level ( r = −0.36, P = 0.02) and significantly associated with the exacerbation frequency ( r = −0.38, P = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency ( r2 = 0.15, P = 0.01). Conclusions: Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations. [ABSTRACT FROM AUTHOR]

The article explores the association between pulmonary emphysema and osteoporosis evaluated by computed tomography (CT) in patients with chronic obstructive pulmonary disease (COPD). Results reveal that the degree of pulmonary emphysema significantly correlated with reduced bone density. The findings suggest that COPD itself could be a risk factor for osteoporosis and that chest CT scanning is useful to menage COPD as a systemic disease.