Project description:BACKGROUND:Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality. Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties. Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs. METHODS:We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs. The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year. RESULTS:Nine RCTs comprising 1666 patients met the inclusion criteria. Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01). Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective. Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates. The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups. A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049). CONCLUSIONS:Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD. However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance. A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages.
Project description:BackgroundAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most common reason for the hospitalization and death of pulmonary patients. The use of antibiotics as adjuvant therapy for AECOPD, however, is still a matter of debate.MethodsIn this study, we searched the PubMed, EmBase, and Cochrane databases for randomized controlled trials published until September 2016 that evaluated the use of antibiotics for AECOPD treatment. The major outcome variables were clinical cure rate and adverse effects. The microbiological response rate, relapse of exacerbation, and mortality were also analysed. A random-effect network was used to assess the effectiveness and tolerance of each antibiotic used for AECOPD treatment.ResultsIn this meta-analysis, we included 19 articles that assessed 17 types of antibiotics used in 5906 AECOPD patients. The cluster ranking showed that dirithromycin had a high clinical cure rate with a low rate of adverse effects. Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole had high clinical cure rates with median rates of adverse effects. In terms of the microbiological response rate, only doxycycline was significantly better than placebo (odds ratio (OR), 3.84; 95% confidence interval (CI), 1.96-7.54; p < 0.001). There were no other significant results with respect to the frequency of recurrence or mortality.ConclusionsOur study indicated that dirithromycin is adequate for improving the clinical cure rate of patients with AECOPD with few adverse effects. Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole are also recommended for disease treatment. However, caution should still be exercised when using antibiotics to treat AECOPD. Trial Registration Not applicable.
Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients. A five chip study using total RNA recovered from Peripheral Blood Mononuclear Cell of Peripheral Blood.Evaluating the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10 after the hospital admission, to compared with healthy controls or patients with stable COPD. Slides were scanned at 5 μm/pixel resolution using an Axon GenePix 4000B scanner (Molecular Devices Corporation) piloted by GenePix Pro 6.0 software (Axon). Scanned images (TIFF format) were then imported into NimbleScan software (version 2.5) for grid alignment and expression data analysis. Expression data were normalized through quantile normalization and the Robust Multichip Average (RMA) algorithm included in the NimbleScan software. The Probe level (*_norm_RMA.pair) files and Gene level (*_RMA.calls) files were generated after normalization.
Project description:Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation. Keywords: other
Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients.
Project description:A systematic review was undertaken to evaluate the efficacy of tiotropium, a long acting anticholinergic drug, on clinical events, symptom scales, pulmonary function, and adverse events in stable chronic obstructive pulmonary disease (COPD).A systematic search was made of the Cochrane trials database, MEDLINE, EMBASE, CINAHL, and a hand search of 20 respiratory journals. Missing data were obtained from authors and the manufacturer. Randomised controlled trials of > or =12 weeks' duration comparing tiotropium with placebo, ipratropium bromide, or long acting beta2 agonists (LABA) were reviewed. Studies were pooled to yield odds ratios (OR) or weighted mean differences with 95% confidence intervals (CI).Nine trials (8002 patients) met the inclusion criteria. Tiotropium reduced the odds of a COPD exacerbation (OR 0.73; 95% CI 0.66 to 0.81) and related hospitalisation (OR 0.68; 95% CI 0.54 to 0.84) but not pulmonary (OR 0.50; 95% CI 0.19 to 1.29) or all-cause (OR 0.96; 95% CI 0.63 to 1.47) mortality compared with placebo and ipratropium. Reductions in exacerbations and hospitalisations compared with LABA were not statistically significant. Similar patterns were evident for quality of life and symptom scales. Tiotropium yielded greater increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline to 6-12 months than did placebo, ipratropium, and LABA. Decline in FEV1 over 1 year was 30 ml (95% CI 7 to 53) slower with tiotropium than with placebo and ipratropium (data were not available for LABA). Reports of dry mouth and urinary tract infections were increased with tiotropium.Tiotropium reduced COPD exacerbations and related hospitalisations, improved quality of life and symptoms, and may have slowed the decline in FEV1. Long term trials are warranted to evaluate the effects of tiotropium on decline in FEV1 and to clarify its role compared with LABA.
Project description:BACKGROUND: Most patients with chronic obstructive pulmonary disease (COPD) receive inhaled long-acting bronchodilators and inhaled corticosteroids. Conventional meta-analyses established that these drugs reduce COPD exacerbations when separately compared with placebo. However, there are relatively few head-to-head comparisons and conventional meta-analyses focus on single comparisons rather than on a simultaneous analysis of competing drug regimens that would allow rank ordering of their effectiveness. Therefore we assessed, using a network meta-analytic technique, the relative effectiveness of the common inhaled drug regimes used to reduce exacerbations in patients with COPD. METHODS: We conducted a systematic review and searched existing systematic reviews and electronic databases for randomized trials of >/= 4 weeks' duration that assessed the effectiveness of inhaled drug regimes on exacerbations in patients with stable COPD. We extracted participants and intervention characteristics from included trials and assessed their methodological quality. For each treatment group we registered the proportion of patients with >/= 1 exacerbation during follow-up. We used treatment-arm based logistic regression analysis to estimate the absolute and relative effects of inhaled drug treatments while preserving randomization within trials. RESULTS: We identified 35 trials enrolling 26,786 patients with COPD of whom 27% had >/= 1 exacerbation. All regimes reduced exacerbations statistically significantly compared with placebo (odds ratios ranging from 0.71 (95% confidence interval [CI] 0.64 to 0.80) for long-acting anticholinergics to 0.78 (95% CI 0.70 to 0.86) for inhaled corticosteroids). Compared with long-acting bronchodilators alone, combined treatment was not more effective (comparison with long-acting beta-agonists: odds ratio 0.93 [95% CI 0.84 to 1.04] and comparison with long-acting anticholinergics: odds ratio 1.02 [95% CI 0.90 to 1.16], respectively). If FEV1 was </= 40% predicted, long-acting anticholinergics, inhaled corticosteroids, and combination treatment reduced exacerbations significantly compared with long-acting beta-agonists alone, but not if FEV1 was > 40% predicted. This effect modification was significant for inhaled corticosteroids (P = 0.02 for interaction) and combination treatment (P = 0.01) but not for long-acting anticholinergics (P = 0.46). A limitation of this analysis is its exclusive focus on exacerbations and lack of FEV1 data for individual patients. CONCLUSION: We found no evidence that one single inhaled drug regimen is more effective than another in reducing exacerbations. Inhaled corticosteroids when added to long-acting beta-agonists reduce exacerbations only in patients with COPD with FEV1 </= 40%.
Project description:BACKGROUND:Metabolic syndrome is a common extrapulmonary comorbidity in patients with chronic obstructive pulmonary disease (COPD). However, the reported relationship of COPD with dyslipidemia, an important component of metabolic syndrome, is ambiguous. The aim of this meta-analysis is to investigate the association between COPD and the serum levels of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), and triglyceride (TG). METHODS:The PubMed and Embase databases were searched to find potential studies using the search terms of ("dyslipidemia" or "HDL" or "LDL" or "cholesterol" or "triglyceride") and COPD. We also performed subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia. Mean differences (MD) with 95% confidence intervals (CI) were estimated with random effects models. RESULTS:A total of 11 studies comprising 615 cases and 471 controls were included in the study. No significant differences were found in the HDL (MD = -2.55, 95% CI [-6.03, 0.93], P = 0.15), LDL (MD = -2.25, 95% CI [-13.36, 8.86], P = 0.69), TC (MD = -2.69, 95% CI [-13.30, 7.92], P = 0.62), and TG (MD = 6.90, 95% CI [-2.81, 16.60], P = 0.16) levels of the 2 groups. However, subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia showed that TG levels were higher in patients with stable COPD than in healthy individuals (MD = 16.35, 95% CI [5.90, 26.80], P = 0.002). CONCLUSIONS:Excluding the impact of hypolipidemic treatment on serum lipid profile, TG levels were higher in patients with COPD than in healthy individuals. This meta-analysis suggested that physicians should screen COPD patients for elevated TG levels to reduce the risk of cardiovascular morbidity and mortality.
Project description:BACKGROUND: Inhaled bronchodilators are the first-line therapy for COPD. Indacaterol is a novel addition to existing long-acting bronchodilators. OBJECTIVES: Systematic review of randomized controlled trials (RCT) ON efficacy and safety of indacaterol as compared: 1) with placebo at different dosages, 2) with existing bronchodilators; (3) as add-on treatment to tiotropium. METHODS: We searched 13 electronic databases, including MEDLINE, EMBASE and CENTRAL, and contacted the manufacturer for unpublished data. Primary outcome was mean FEV1 change at 12(th) week, secondary outcomes included changes in SGRQ, TDI and BODE index at 6 months, exacerbation at 1 year, and worsening of symptoms. RESULTS: Twelve eligible RCTs of moderate risk of bias included data from 10,977 patients. Compared to placebo, indacaterol improved FEV1 by a weighted mean difference (WMD) of 0.16 L (95%CI: 0.15, 0.18 L, p<0.001), homogeneously above the minimally important difference of 0.10 L. It offered clinically relevant improvement in all secondary outcomes except exacerbation. Magnitude of benefit did not differ significantly by dosage, but one treatment related death was reported at 300 ug. Efficacy of Indacaterol was similar to formoterol and salmeterol (FEV1 WMD?=?0.04 L, 95%CI: 0.01 L, 0.07 L, p?=?0.02); and tiotropium (FEV1 WMD?=?0.01 L, 95%CI: -0.01, 0.03 L, p?=?0.61). The use of indacaterol on top of tiotropium yielded additional improvement on FEV1 (WMD?=?0.07 L, 95%CI: 0.05 L, 0.10 L, p<0.001). CONCLUSION: Indacaterol is safe and beneficial for patients with COPD at dosage ?150 ug. It may serve as a good alternative to existing bronchodilators, or as an add-on to tiotropium for unresponsive patients. Use of higher dosage requires further justification.