噻托溴铵在中重度哮喘中的作用——meta分析-东南大学学报医学版

噻托溴铵在中重度哮喘中的作用——meta分析

单位：1. 东南大学附属中大医院呼吸科, 江苏南京 210009;
2. 东南大学医学院, 江苏南京 210009

分类号：R562.25

出版年·卷·期（页码）：2015·34·第六期（946-952）

摘要：

目的:评估噻托溴铵在标准治疗仍控制不佳的中重度哮喘中的疗效及安全性.方法:以"tiotropium"、"spiriva"和"asthma"为检索词,检索PubMed、EMBASE、CENTRAL数据库和ClinicalTrial.gov;以"噻托溴铵"、"思力华"、"速乐"和"哮喘"为检索词检索万方数据库、中国期刊全文数据库(CNKI)及中国生物医学文献数据库(CBMdisc),检索时间为1980年1月至2014年10月.选取采用了随机双盲对照,并且治疗时间大于4周的临床研究予以纳入.逐个进行质量评价和资料提取.运用RevMan 5.3.5软件对所获数据进行统计分析,计数资料采用优势比(odds ratios,OR),计量资料采用加权均数差(weighted mean difference,WMD).对比噻托溴铵和安慰剂对入选患者肺功能(最大呼气流量,peak expiratory flow,PEF;第一秒用力呼气容积,forced expiratory volume in one second,FEV₁)、急救药物的使用次数(喷·d^-1)、夜间唤醒次数、哮喘控制情况(Asthma Control Questionnaire-7,ACQ-7)、哮喘生活质量(Asthma Quality of Life Questionnaire,AQLQ)及副作用的影响.结果:通过筛选共纳入9篇文献,其中1篇包括了2个临床试验,故共纳入10个随机对照临床研究,包括5篇平行随机对照研究和5篇交叉随机对照研究,总计3 892例患者.噻托溴铵治疗哮喘可以改善晨起PEF(WMD 21.25 L·min^-1,95% CI 17.54~24.97 L·min^-1,P<0.000 01,I²=0%)及夜间PEF(WMD 23.05 L·min^-1,95%CI 19.60~26.50 L·min^-1,P<0.000 01,I²=38%);提高Peak FEV₁(WMD 0.16 L,95%CI 0.13~0.19 L,P<0.000 01,I²=39%)和Trough FEV₁(WMD 0.09 L,95%CI 0.07~0.12 L,P<0.000 01,I²=52%);减少不良事件的发生(OR 0.80,95%CI 0.67~0.95,P=0.009,I²=0%).虽然经过汇集分析显示加用噻托溴铵治疗后ACQ-7评分(WMD-0.14,95%CI-0.20~-0.08,P<0.00001,I²=0%)和AQLQ评分(WMD 0.08,95%CI0.01~0.14,P=0.02,I²=0%)有所降低,但没有达到临床意义的最小差别.治疗的最后1周夜间唤醒次数(WMD 0.00,95%CI-0.06~0.05,P=0.87,I²=0%)、每天急救药物使用次数(喷·d^-1)(WMD-0.04,95%CI-0.18~0.11,P=0.63,I²=0%)和严重不良事件的发生(OR 1.01,95%CI 0.69~1.47,P=0.96,I²=0%)差异均无统计学意义.结论:噻托溴铵治疗经标准治疗控制不佳的哮喘患者是安全和有效的,可以改善肺功能,减少不良事件的发生,亦没有增加严重不良事件的发生.噻托溴铵治疗哮喘有一定的应用前景.

Objective: To evaluate the efficacy and safety of tiotropium in moderate-to-severe asthma still uncontrolled after standard treatment. Methods: Using "tiotropium", "spiriva" and "asthma" as key words, an electronic and manual search was conducted in the databases PubMed, EMBASE, CENTRAL, ClinicalTrial.gov, Wanfang Data, CNKI and CBMdisc from Jan, 1980 to Oct, 2014. Which included clinical trials of random double blind controls and lasting 4 weeks and longer. Quality assessment and data extraction of the included articles were performed. Weighted mean difference(WMD) for peak expiratory flow(PEF), forced expiratory volume in one second(FEV₁), night waking due to asthma or limitation of activity, frequency of reliever use for symptoms relief, Asthma Control Questionnaire-7(ACQ-7) and Asthma Quality of Life Questionnaire (AQLQ), pooled odds ratios(OR) for occurrence of adverse events and serious adverse events were calculated between the tiotropium treated group and the placebo group using software Revman5.3.5. Results: Nine articles fulfilled the inclusion criteria. One of them had two clinical trials. So ten randomized controlled clinical studies were included in the meta-analysis, including five parallel randomized controlled studies and five crossover randomized controlled studies. In the 3 892 patients, results showed tiotropium could improve morning and night PEF, Peak and Trough FEV₁, and reduce the occurrence of adverse events. Even though ACQ-7 and AQLQ diminished somewhat, it had no clinical significance. Night waking due to asthma or limitation of activity, frequency of reliever use for symptom relief and occurrence of serious adverse events during the last week of treatment also did not have clinical significance. Conclusion: Tiotropium in the treatment of poorly controlled asthma patients who have received standard treatment is safe and effective. It can improve pulmonary function, reduce the incidence of adverse events without increasing serious ones. It is hypothesized that tiotropium in treating asthma has certain prospect in application.

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