International journal of chronic obstructive pulmonary disease
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Int J Chron Obstruct Pulmon Dis · Jan 2017
Pri-microRNA-124 rs531564 polymorphism minor allele increases the risk of pulmonary artery hypertension by abnormally enhancing proliferation of pulmonary artery smooth muscle cells.
MicroRNA-124 (miR-124) has been reported to be downregulated in the cells exposed to hypoxia, which was confirmed in our study. We then used online microRNA target prediction tools to identify GRB2, SMAD5, and JAG1 as the candidate target genes of miR-124, and we next validated GRB2 as a direct gene by using luciferase reporter system. We also established the regulatory relationship between miR-124 and GRB2 by showing the negative linear relationship between GRB2 and miR-124 expression. ⋯ Meanwhile, we also conducted real-time polymerase chain reaction and Western blot analysis to study the expression of GRB2 among different genotypes or pulmonary artery smooth muscle cells (PASMCs) treated with miR-124 mimics, GRB2 small interfering RNA, and miR-124 inhibitors, respectively, and found that introduction of miR-124 or GRB2 small interfering RNA could reduce the expression of GRB2 and inhibit the proliferation of PASMCs, while miR-124 upregulated the expression of GRB2 and promoted the proliferation of PASMCs. A total of 412 COPD patients with PAH (n=182) or without PAH (n=230) were recruited in this study, and more individuals carrying at least one minor allele of rs531564 were found in the COPD patients with PAH than in those without PAH (odds ratio: 0.61, 95% confidence interval: 0.41-0.91; P=0.166). In conclusion, the presence of rs531564 minor allele may increase the risk of PAH in COPD by reducing miR-124 expression, increasing GRB2 expression, and promoting the proliferation of PASMCs.
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Int J Chron Obstruct Pulmon Dis · Jan 2017
Pre- and post-bronchodilator airway obstruction are associated with similar clinical characteristics but different prognosis - report from a population-based study.
According to guidelines, the diagnosis of COPD should be confirmed by post-bronchodilator (post-BD) airway obstruction on spirometry; however, in clinical practice, this is not always performed. The aim of this population-based study was to compare clinical characteristics and prognosis, assessed as mortality, between subjects with airway obstruction divided into pre- but not post-BD obstruction, post-BD airway obstruction (COPD), and subjects without airway obstruction. ⋯ Even though subjects with COPD and pre- not post-BD obstruction had fairly similar presentation of clinical characteristics, only those with COPD, specifically GOLD stage ≥2, had increased risk for death when compared with nonobstructive subjects.
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Int J Chron Obstruct Pulmon Dis · Jan 2017
Review Meta AnalysisEffect of carbocisteine on patients with COPD: a systematic review and meta-analysis.
COPD is the fourth leading cause of death in the world. It is a common, progressive, treatable and preventable disease. The exacerbation of COPD is associated with the peripheral muscle force, forced expiratory volume in 1 second (FEV1), the quality of life and mortality. Many studies indicated that the mucoactive medicines could reduce the exacerbations of COPD. This study summarized the efficacy of carbocisteine as a treatment for COPD. ⋯ Long-term use of carbocisteine (500 mg TID) may be associated with lower exacerbation rates, the smaller number of patients with at least one exacerbation and higher quality of life of patients with COPD.
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Int J Chron Obstruct Pulmon Dis · Jan 2017
Review Meta AnalysisLABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis.
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments. The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD. ⋯ The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD. These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.
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Int J Chron Obstruct Pulmon Dis · Jan 2017
Randomized Controlled Trial Multicenter StudyImprovement in 24-hour bronchodilation and symptom control with aclidinium bromide versus tiotropium and placebo in symptomatic patients with COPD: post hoc analysis of a Phase IIIb study.
A previous Phase IIIb study (NCT01462929) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium, and improvement of symptoms versus placebo. This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study. ⋯ In this post hoc analysis of symptomatic patients with moderate to severe COPD, aclidinium 400 μg BID provided additional improvements compared with tiotropium 18 μg QD in: 1) bronchodilation, particularly during the nighttime, 2) daily COPD symptoms (E-RS), 3) early-morning and nighttime symptoms, and 4) early-morning limitation of activity.