罗氟司特治疗稳定期慢性阻塞性肺疾病的疗效及其安全性的Meta分析

目的研究罗氟司特对稳定期慢性阻塞性肺疾病（COPD）的疗效及安全性。 方法检索Pubmed、EMBASE、CINAHL、Cochrane clinical trials database、ScienceDirect.gov、中国生物医学文献数据库、万方数据数字化期刊全文数据库、维普数据数字化期刊全文数据库、中国期刊全文数据库等数据库1995年1月至2014年7月的论文，将罗氟司特治疗COPD慢性阻塞性肺疾病Ⅱ/Ⅲ期临床实验的相关文章纳入本研究。观察支气管肺功能、加重风险、健康相关生活质量、不良反应等。用修改后的Jadad量表和Cochrane偏倚风险评估工具对纳入研究质量进行评估。计量资料计算加权均数差（WMD）和95%可信区间（95%CI），计数资料计算比值比（OR）。用I²进行异质性检验。 结果共纳入7篇文献，包含9项随机对照研究。罗氟司特可分别提高支气管舒张前后的一秒用力呼气容积（WMD=57.56，95%CI：48.03~67.10，Z=11.83；WMD=63.97，95%CI：54.01~73.92，Z=12.60，P均<0.05）、用力肺活量（WMD=86.8，95%CI：66.00~107.60，Z=8.18；WMD=89.63 ml，95%CI：70.50~108.77，Z=9.18，P均<0.05）、最大呼气流速（FEF）25%~75%（WMD=21.26，95%CI：11.50~31.03，Z=4.27；WMD=23.04，95%CI：14.17~31.91，Z=5.09，P均<0.05），降低COPD的总体加重率（OR=-0.16，95%CI：-0.24~-0.08，Z=3.74，P<0.05）、中度加重率（OR=-0.08，95%CI：-0.15~-0.02，Z=2.43，P=0.02），延长第一次中重度加重时间（WMD=9.65 min，95%CI：5.31~13.98，Z=4.30，P<0.05），并可提高过渡期呼吸困难指数评分（WMD=0.3，95%CI：0.16~0.44，Z=4.24，P<0.05）。而对重度加重率（OR=0.00，95%CI：-0.02~0.02，Z=0.40，P=0.69），第二次中重度加重时间（WMD=28.24，95%CI：-2.13~58.62，Z=1.82，P=0.07）的影响无统计学意义。罗氟司特治疗相关不良反应主要涉及消化系统、神经系统症状，主要出现在治疗的前4周，有自限趋势。 结论罗氟司特有望成为COPD稳定期的新型抗炎治疗药物。

Efficacy and safety of roflumilast in patients with stable chronic obstructive pulmonary disease: a meta-analysis

ObjectiveTo investigate the efficacy and safety of roflumilast in patients with stable chronic obstructive pulmonary disease (COPD). MethodsPubMed, EMBASE, CINAHL, Cochrane clinical trials database, ScienceDirect, Chinese biomedical literature database, Wanfang, Weipu database, and Chinese periodical database were searched for articles about Phase Ⅱ/Ⅲ clinical trials in patients with COPD treated with roflumilast, published from January 1995 to July 2014. The parameters of lung function, the aggravated risk of COPD, the health-related quality of life and the adverse effects were evaluated. The Jadad scale and the Cochrane collaboration's tool for assessing risk of bias were respectively used for evaluating the RCTs. Meta-analysis was performed using an inverse-variance model, providing weighted mean difference (WMD) and 95% confidence intervals (CI). Heterogeneity was determined by I² statistic. ResultsA total of 7 eligible studies were identified, including 9 randomized controlled trials. The forced expiratory volume in one second (WMD=57.56, 95%CI: 48.03~67.10, Z=11.83; WMD=63.97, 95%CI: 54.01~73.92, Z=12.60, all P<0.05), forced vital capacity (WMD=86.8, 95%CI: 66.00~107.60, Z=8.18; WMD=89.63, 95%CI: 70.50~108.77, Z=9.18, all P<0.05) and forced expiratory flow between 25% and 75% of vital capacity (WMD=21.26, 95%CI: 11.50~31.03, Z=4.27; WMD=23.04, 95%CI: 14.17~31.91, Z=5.09, all P<0.05) before and after bronchodilator increased in the roflumilast group, respectively. The overall exacerbation rate (OR=-0.16, 95%CI: -0.24~-0.08, Z=3.74, P<0.05) and the moderate exacerbation rate (OR=-0.08, 95%CI: -0.15~-0.02, Z=2.43, P=0.02) were reduced, the time to first moderate-severe exacerbation were prolonged (WMD=9.65, 95%CI: 5.31~13.98, Z=4.30, P<0.05), transition dyspnea index significantly increased (WMD=0.3, 95%CI: 0.16~0.44, Z=4.24, P<0.05) in patients treated with roflumilast, while no statistical differences were noted in severe exacerbation rate (OR=0.00, 95%CI: -0.02~0.02, Z=0.40, P=0.69) and the time to second moderate-severe exacerbation (WMD=28.24, 95%CI: -2.13~58.62, Z=1.82, P=0.07). The adverse effects related to treatment are mainly involved in the digestive system and nervous system, mainly occurred during the first 4 weeks after treatment and existed self-limited up to down course. ConclusionAs a novel anti-inflammatory drug, roflumilast is likely to treat the patients with stable COPD.