Objective: To evaluate the efficacy and safety of tiotropium Respimat in the treatment of chronic obstructive pulmonary disease (COPD) according to the Cochrane systematic evaluation. Methods: The Cochrane Library, PubMed, EMbase, CNKI, VIP and CBM, Wanfang Data were searched(from the foundation date to Jan. 2016) for the randomized controlled trials (RCTs) of tiotropium Respimat in the treatment of patients with COPD. Two reviewers independently retrieved the RCTs according to the inclusion and exclusion criteria, assessed the methodological quality of the included trials.and performed statistical analysis on the data using RevMan 5.3 software. Results: Totally 11 RCTs on efficacy were finally included.The results of the combined analysis showed that FEV(1) was significantly improved in the tiotropium Respimat group than that in the placebo group[MD=0.12, 95%CI(0.10-0.14), P<0.000 01], while FEV(1) was similar between the tiotropium Respimat group and the tiotropium HandiHaler group[5 μg: MD=0.00, 95%CI(-0.04-0.04), P=0.94; 2.5 μg: MD=-0.04, 95%CI(-0.10-0.01), P=0.12; 10 μg: MD=0.02, 95%CI(-0.06-0.09), P=0.66]. FVC was significantly improved in the tiotropium Respimat group than that in the placebo group[MD=0.18, 95%CI(0.09-0.28), P=0.0002], while FVC was similar between the tiotropium Respimat group and the HandiHaler group[2.5 μg: MD=-0.06, 95%CI(-0.16-0.04), P=0.24; 5 μg: MD=-0.00, 95%CI(-0.08-0.08), P=1.00; 10 μg: MD=0.02, 95%CI(-0.14-0.19), P=0.78]. The risk of acute exacerbations was lower in the tiotropium Respimat group (5 μg / kg) than in the placebo group [OR=0.72, 95%CI(0.60-0.86), P=0.000 3]. It was similar in the tiotropium Respimat group (5 μg) and the HandiHaler group[OR=1.01, 95%CI(0.94-1.09), P=0.71]. The SGRQ total score of the tiotropium Respimat group (5 μg) was significantly different from that of the placebo group[MD=-3.6, 95%CI(-3.88--3.32), P<0.000 01]. C(max, ss) and AUC(0-6 h, ss) were also similar between the tiotropium Respimat group and the HandiHaler group[MD=0.2, 95%CI(-5.1-5.5), P=0.94]; MD=-1.01, 95%CI(-11.78-9.77), P=0.85]. Nine RCTs were included in the evaluation of the incident rates of adverse drug reactions(ADR). There was no significant difference between the tiotropium Respimat group HandiHaler group and the placebo group[RR=0.95, 95%CI(0.89-1.00), P=0.05], [OR=1.07, 95%CI(1.00-1.16), P=0.06]. Conclusions: The efficacy and safety of tiotropium Respimat was similar to tiotropium HandiHaler in the treatment of COPD. They can effectively improve the pulmonary function and clinical symptoms of patients. But the long-term efficacy and safety of tiotropium Respimat still need to be confirmed by higher quality and larger RCTs with long-term follow-up.
目的： 系统评价噻托溴铵喷雾剂治疗慢性阻塞性肺疾病(慢阻肺)的疗效和安全性。 方法： 以"tiotropium respimat"、"tiotropium bromide spray"、"chronic obstructive pulmonary disease"、"COPD"、"randomized"、"controlled"、"randomly"为英文检索词，"噻托溴铵喷雾剂"、"慢阻肺"、"慢性阻塞性肺疾病"、"随机对照"为中文检索词，分别检索Cochrane Library、PubMed、EMbase、中国知网、维普数据、中国生物医学文献数据库和万方数据，各数据库检索时间均从建库至2016年10月。按照Cochrane系统评价方法检索噻托溴铵喷雾剂治疗慢阻肺的所有随机对照试验(RCT)，2名研究者按照纳入排除标准进行数据提取和质量评价，采用RevMan 5.3软件进行统计分析。 结果： 共纳入11个RCT研究，对文献进行不同指标分析：在改善患者FEV(1)水平方面，噻托溴铵喷雾剂组(5 μg/吸)优于安慰剂组[MD＝0.12，95%CI(0.10～0.14)，P<0.01]。不同剂量噻托溴铵喷雾剂组均与粉吸入剂组疗效相似[5 μg: MD＝0.00，95%CI(－0.04～0.04)，P＝0.94；2.5 μg：MD＝－0.04，95%CI(－0.10～0.01)，P＝0.12；10 μg：MD＝0.02，95%CI(－0.06～0.09)，P＝0.66]。在改善患者FVC水平方面，噻托溴铵喷雾剂组(5 μg/吸)优于安慰剂组[MD＝0.18，95%CI(0.09～0.28)，P<0.01]。不同剂量噻托溴铵喷雾剂组与粉吸入剂组疗效相似[2.5 μg：MD＝－0.06，95%CI(－0.16～0.04)，P＝0.24；5 μg：MD＝－0.00, 95%CI(－0.08～0.08)，P＝1.00；10 μg：MD＝0.02，95%CI(－0.14～0.19)，P＝0.78]。在急性加重风险方面，噻托溴铵喷雾剂组(5 μg/吸)发生急性加重的风险较安慰剂组低[OR＝0.72, 95%CI(0.60～0.86)，P<0.01]。噻托溴铵喷雾剂组(5 μg/吸)和粉吸入剂组发生急性加重风险相似[OR＝1.01, 95%CI(0.94～1.09)，P＝0.71]。圣乔治呼吸问卷评分上，噻托溴铵喷雾剂组(5 μg/吸)优于安慰剂组[MD＝－3.6, 95%CI(－3.88～－3.32)，P<0.01]。噻托溴铵喷雾剂组(5 μg/吸)和粉吸入剂组在稳态时的最大血药浓度、血药浓度-时间曲线下面积均相似[MD＝0.2, 95%CI(－5.1～5.5)，P＝0.94]；MD＝－1.01, 95%CI(－11.78～9.77)，P＝0.85]。安全性部分纳入9项RCT研究，噻托溴铵喷雾剂组(5 μg/吸)与安慰剂组及粉吸入剂组的不良反应发生率均相似[RR＝0.95, 95%CI(0.89～1.00)，P＝0.05，OR＝1.07, 95%CI(1.00～1.16)，P＝0.06]。 结论： 噻托溴铵喷雾剂与粉吸入剂具有相似的疗效，均能有效改善慢阻肺患者肺功能及临床症状，且安全性较好；但其远期疗效及安全性有待长期随访的RCT研究结果验证。.
Keywords: Pulmonary disease, chronic obstructive; Randomized controlled trial; Systematic review; Tiotropium Respimat.