罗氟司特对亚洲慢性阻塞性肺疾病患者肺功能影响的Meta分析

目的:系统评价罗氟司特对亚洲慢性阻塞性肺疾病(COPD)患者肺功能的影响,为临床合理用药提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、Embase、中国生物医学文献数据库、中国知网、维普数据库和万方数据库,收集罗氟司特或罗氟司特联合常规治疗或安慰剂(试验组)对比常规治疗或安慰剂治疗(对照组)治疗亚洲人群COPD的随机对照试验(RCT)。筛选文献,提取资料并按照Cochrane偏倚风险评估工具评价文献质量后,采用Rev Man 5.2软件进行Meta分析。结果:共纳入6项RCT,包括1 494例患者。Meta分析结果显示,试验组患者支气管扩张药使用前第1秒用力呼气容积MD=75.19,95%CI(53.21,97.17),P<0.000 01]、支气管扩张药使用后第1秒用力呼气容积MD=56.60,95%CI(27.56,85.63),P=0.000 1]、用力肺活量MD=43.67,95%CI(15.91,71.43),P=0.002]、支气管扩张药使用后25%～75%用力肺活量的平均流速MD=14.58,95%CI(8.43,20.73),P<0.001]、腹泻发生率RR=5.06,95%CI(1.26,20.27),P=0.02]、呼吸道感染发生率RR=1.94,95%CI(1.30,2.90),P=0.001]、食欲下降发生率RR=7.43,95%CI(2.94,18.79),P=0.001]、体质量下降发生率RR=5.46,95%CI(2.12,14.03),P=0.001]、头痛发生率RR=7.73,95%CI(1.42,42.16),P=0.02]、头晕发生率RR=3.44,95%CI(1.28,9.27),P=0.01]、胃炎发生率RR=5.09,95%CI(1.49,17.45),P=0.01]、厌食症发生率RR=5.06,95%CI(1.97,13.00),P=0.001]均显著高于对照组;圣乔治呼吸问卷总评分MD=-5.82,95%CI(-7.77,-3.87),P<0.001]、呼吸症状评分MD=-1.67,95%CI(-2.51,-0.84),P<0.001]、活动受限评分MD=-1.55,95%CI(-2.14,-0.97),P<0.001]、疾病影响评分MD=-2.59,95%CI(-3.40,-1.79),P<0.001]均显著低于对照组。结论:罗氟司特可改善亚洲COPD患者的肺功能及呼吸困难症状,但会增加不良反应的发生风险。

Effects of Roflumilast on Lung Function of Asian Patients with Chronic Obstructive Pulmonary Disease:a Meta-analysis

OBJECTIVE:To systematically evaluate the effects of roflumilast on lung function of Asian patients with chronic obstructive pulmonary disease(COPD),and to provide evidence-based reference for rational drug use in the clinic. METHODS: Retrieved from Cochrane library,PubMed,Embase,CBM,CNKI,VIP and Wanfang database,RCTs about roflumilast or roflumilast combined with routine treatment or placebo (trial group) versus routine treatment or placebo (control group) in the treatment of Asian COPD patients were collected. After literature screening,data extraction and quality evaluation with Cochrane bias risk evaluation tool,Meta-analysis was conducted by using Rev Man 5.2 software. RESULTS:Totally 6 RCTs were included, involving 1 494 patients. Meta-analysis showed that pre-bronchodilator FEV1(pre-FEV1)MD=75.19,95%CI(53.21,97.17),P< 0.000 01],post-bronchodilator FEV1(post-FEV1)MD=56.60,95%CI(27.56,85.63),P=0.000 1],forced vital capacity(FVC)MD=43.67,95% CI(15.91,71.43),P=0.002],average flow rate of post-bronchodilator 25%-75% of forced vital capacity (post-FEF25%-75%)MD=14.58,95%CI(8.43,20.73),P<0.001],the incidence of diarrhea RR=5.06,95%CI(1.26,20.27), P=0.02],respiratory infection RR=1.94,95% CI(1.30,2.90),P=0.001],decreased appetite RR=7.43,95% CI(2.94, 18.79),P=0.001],body weight decrease RR=5.46,95% CI(2.12,14.03),P=0.001],headache RR=7.73,95% CI(1.42, 42.16),P=0.02],dizziness RR=3.44,95%CI(1.28,9.27),P=0.01],gastritis RR=5.09,95%CI(1.49,17.45),P=0.01]and anorexia RR=5.06,95% CI(1.97,13.00),P=0.001] in trial group were significantly higher than control group;St. George’s Respiratory Questionnaire (SGRQ) total score MD=- 5.82, 95% CI(- 7.77,- 3.87), P<0.001], respiratory symptom score MD=- 1.67,95% CI (- 2.51,- 0.84), P<0.001], activity limited score MD=- 1.55,95%CI(-2.14,-0.97),P<0.001] and disease impact score MD=-2.59,95%CI(-3.40,-1.79),P<0.001] of trial group were significantly lower than those of control group. CONCLUSIONS:Roflumilast can improve lung function and dyspnea in Asian COPD patients,but it can increase the risk of ADR.