氨溴索联合乙酰半胱氨酸治疗慢性阻塞性肺疾病急性加重有效性和安全性的Meta分析

Meta-analysis of the effectiveness and safety of ambroxol combined with acetylcysteine for acute exacerbations of chronic obstructive pulmonary disease

目的系统评价氨溴索联合乙酰半胱氨酸治疗慢性阻塞性肺疾病急性加重(AECOPD)的疗效和安全性,为临床合理用药使用提供循证医学证据。方法系统检索CBM、CNKI、VIP、WanFang、PubMed、Embase、Web of Science、The Cochrane Library、ClinicalTrials数据库,收集氨溴索联合乙酰半胱氨酸治疗对比氨溴索单药治疗AECOPD的随机对照试验(RCTs),检索时间从建库至2022年11月。将检索的文献由2位评价员独立筛选文献、提取资料和评价质量,采用RveMan 5.4进行Meta分析。结果共纳入17篇RCT,收集到1454例患者,所纳入的文献质量较低。Meta分析结果显示,与单用氨溴索治疗相比,氨溴索联合乙酰半胱氨酸治疗AECOPD能显著提高总有效率[RR=1.24,95%CI(1.18,1.30),P<0.00001]、一秒用力呼气容积(FEV1)/用力肺活量(FVC)[MD=5.92,95%CI(4.95,6.88),P<0.00001]、FEV1[MD=0.29,95%CI(0.23,0.34),P<0.00001]及氧分压水平[MD=11.88,95%CI(8.78,14.98),P<0.00001],降低二氧化碳分压[MD=-9.38,95%CI(-10.78,-7.99),P<0.00001]、C反应蛋白(CRP)水平[CRP≥50 mg·L^(-1),MD=-11.34,95%CI(-13.11,-9.56),P<0.00001;CRP≤50 mg·L^(-1),MD=-3.54,95%CI(-4.62,-2.46),P<0.0001]。两组不良反应发生率无显著差异[RR=0.69,95%CI(0.44,1.10),P=0.12]。结论相比氨溴索单药治疗,氨溴索联合乙酰半胱氨酸治疗AECOPD的有效率较高,不良反应发生率轻微。但受文献质量和数量的影响,还需进行多中心、大样本、高质量的RCTs进行验证。

Objective To systematically evaluate the effectiveness and safety of ambroxol combined with acetylcysteine for acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and provide evidence for rational use of drugs.Methods CBM,CNKI,VIP,WanFang,PubMed,Embase,Web of Science,The Cochrane Library,and ClinicalTrials databases were searched for relevant randomized controlled trials(RCTs)of ambroxol combined with acetylcysteine verse ambroxol monotherapy for AECOPD from the inception of the databases to November 2022.All the retrieved papers were screened,and evaluated by two independently researchers,followed by meta-analysis by Rev Man 5.4.Results Totally 17 RCTs were included,involving 1454 patients.The quality of the included research was low.The meta-analysis showed that ambroxol combined with acetylcysteine for AECOPD significantly increased the total effective rate[RR=1.24,95%CI(1.18,1.30),P<0.00001],the value of forced expiratory volume in one second(FEV1)/forced vital capacity(FVC)[MD=5.92,95%CI(4.95,6.88),P<0.00001];FEV1 value[MD=0.29,95%CI(0.23,0.34),P<0.00001],and the oxygen partial pressure level[MD=11.88,95%CI(8.78,14.98),P<0.00001].The reduced carbon dioxide partial pressure[MD=-9.38,95%CI(-10.78,-7.99),P<0.00001]and C-reactive protein(CRP)levels[for CRP≥50 mg·L^(-1)group,MD=-11.34,95%CI(-13.11,-9.56),P<0.00001;for CRP≤50 mg·L^(-1)group,MD=-3.54,95%CI(-4.62,-2.46),P<0.0001]as compared with ambroxol monotherapy.There was no significant difference in the incidence of adverse reactions between the two groups[RR=0.69,95%CI(0.44,1.10),P=0.12].Conclusion Compared with ambroxol monotherapy,ambroxol combined with acetylcysteine is more effective for AECOPD,and the incidence of adverse reactions is light.However,due to the quality and quantity of literatures,multi-center and high-quality RCTs with large sample sizes are needed for verification.