大环内酯类药物预防慢性阻塞性肺疾病急性发作的Meta分析

Meta Analysis of Macrolides in the Prevention of Acute Exacerbation of Chronic Obstructive Pulmonary Disease ABSTRACT

目的慢性阻塞性肺疾病急性发作(AECOPD)可以导致高住院率和高死亡率。慢性阻塞性肺疾病急性发作(AECOPD)与气道炎症加重和细菌感染有关,大环内酯类抗生素是一类同时具有抗菌作用和抗炎作用以及免疫调节作用的药物。本研究采用发表的随机对照试验进行Meta分析,探讨大环内酯类药物预防慢性阻塞性肺病的急性发作期有效性和安全性。方法通过检索PUBMed、Embase、Cochrane Library、CNKI、EBM数据库,检索出随机对照试验相关文献,并使用RevMan5.3软件进行Meta分析,评价大环内酯类药物是否能预防AECOPD的发生。主要结局指标是随访期间试验组与对照组患者至少发生一次急性加重的频次,次要结局指标包括住院率、死亡率、SGRQ(圣乔治呼吸问卷)评分、不良反应事件等。结果纳入文献包括10项RCT试验,1702名患者。对纳入的研究进行Meta分析后结果显示,大环内酯类药物能显著减少COPD患者至少发生一次急性加重的频次(RR=0.67, 95%CI:0.55-0.83, P<0.05,Ⅰ2=63%),即使用大环内酯类药能预防COPD急性发作。亚组分析显示只有使用红霉素或阿奇霉素疗程6-12个月才有效,大环内酯类药能显著降低患者住院率(RR=0.76, 95%CI:0.64-0.90, P<0.05,Ⅰ2=0%),不能显著减少SGRQ总评分(Mean difference=-4.42, 95%CI:-8.79 to-0.04, P=0.05,Ⅰ2=95%),总的不良反应发生事件率与死亡率在治疗组与对照组之间无显著性差异。结论使用红霉素或阿奇霉素治疗6-12个月,可有效减少COPD患者至少发生一次急性发作频率,降低因急性加重住院的住院率,不能提高患者日常生活质量(SGRQ评分),而且大环内酯类药物不会显著增加患者不良反应事件的发生。对于死亡率,大环内酯类药物与对照组并无显著差异性,得出大环内酯类药物并不会显著降低患者死亡率。然而纳入文献数量较少,因此我们使用这些结论必须要谨慎,今后需要更多设计科学严谨的前瞻性随机对照双盲的高质量试验来支持。

Objective The acute episode of chronic obstructive pulmonary disease (AECOPD) can lead to high hospitalization rates and high mortality rates. The acute episode of chronic obstructive pulmonary disease(AECOPD) is associated with airway inflammation and bacterial infection.The macrolide antibiotics are a class of drugs that have both antibacterial, anti-inflammatory effects and immune regulation, so the macrolides can effectively prevent AECOPDs attack. In this study, meta analysis of published randomized controlled trials was conducted to investigate the feasibility and safety of macrolides in the prevention of acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods By retrieving the pubmed, embase, cochrane library databases,CNKI, EBM, a meta-analysis of the rct-related literature was conducted to evaluate the occurrence of preventive macrolides in preventing aecopds. The first outcome measure was the frequency of at least one acute exacerbation in the trial group and the control group during follow-up in the literature.The second measure including hospitalization rate,mortality,SGRQ score and adverse events. Results A meta-analysis of the included studies showed that macrolides significantly reduced the frequency of at least one acute exacerbation in copd patients(RR=0.67,95%CI:0.55-0.83, F<0.05,Ⅰ^2=63%), using macrolides to prevent acute onset of COPD. The subgroup analysis showed that the use of erythromycin or azithromycin for 6-12 months was effective, and macrolides could significantly reduce the patient's hospitalization(RR=0.76,95% CI:.64-0.90, P<0.O5,Ⅰ^2 =%). Macrolides could not significantly reduce the total SGRQ score(Meandiffirence=-4.42,95%CI=-8.79 to -0.04, P=0.05,Ⅰ^2=95%). There was no significant difference in the incidence of adverse events and mortality between the treatment group and the control group.Conclusion Our results suggest that 6-12 months of erythromycin or azithromycin treatment can effectively reduce the frequency of acute episodes in patients with copd and reduce hospitalization rates for acute exacerbation. Not improve the quality of daily life of patients with SGRQ scores, although macrolides may increase the incidence of adverse events in patients. However, there is no significant difference between macrolides and the control group, suggesting that macrolides can not significantly reduce the mortality of patients. The quality is low, so we have to becareful in using these conclusions, and more scientifically rigorous, prospective, randomized, double-blind, high-quality trials are needed in the future.