长效β2激动剂／吸入激素联合吸入剂与增加吸入激素量治疗哮喘的对比研究

Combination therapy with single inhaler of long-acting β2-adrenoceptor agonists/inhaled corticosteroids compared with higher dose of inhaled corticosteroids in asthmatic patients

目的系统分析长效β2激动剂／吸入激素联合吸入剂（ICS／LABA）与增加吸入激素（ICS）量治疗哮喘的放果．定量评估联合治疗效能及临床安全性。方法应用＂ Fluticasone arid salmerterol＂ ＂budesonide/formoterol＂ ,＂ Serctide＂ ,＂ Advair＂ ＂ Symbicort Turbuhaler＂,联合“Randomised controlied trial”，检索1997年1月至2009年12月Medline和Embase两大数据库收录的文献。也检索了GlaxoSnfithKline临床试验登记数据库、Cochrane列照研究登记数据库，并辅以文献追溯以获得另外的研究或者纳入研究的详细资料。结果联合吸入剂组较至少增加一倍以上吸入激素组晨间呼气峰流速、晚间呼气峰流速及临床FEV1在研究终点分别增加17．59L／min、14．95L／min和0．08L／min（P〈0．01）。哮喘急性发作前者较后者有统计学意义的下降，OR值为0．61（95%．C10．53—0．70，P〈0．01）．无症状天数、哮喘控制天数和未使用缓解症状药物天数的百分数等前者较后者分别增加6．30（95％CI3．52—9．10，P〈0．01）、9．49（95％C14．74-14．25，P〈0．01）和6．59（95％C16．10～7．08，P〈0．01）。沙丁胺醇气雾剂的揿数下降0．22（95％C10．11-0，33，P〈0．01）。两组总体不良反应差异无统计学意义。结论ICS／LABA联合剂比增加ICS剂量更能改善肺功能．降低哮喘急性发作，增加哮喘控制天数，其疗效优于增加ICS剂量，且简化应用。

Objective To provide a quantitative summary estimate on the efficacy and safety measures of tile combination therapy. Methods We searched databases （ Medline and Embase） from January 1997 to December 2009 using＇ Fluticasone and salmerterol＇ or＇ Seretide＇ or＇ Advair＇ or＇ budesonide/formoterol＇ or＇ S）;mbicort ＇Turbuhaler＇ in combination with ＇ Randomised controlled trial＇. The databases of GlaxoSmithKline Clinic＇a] Trial Register and Cochrane Controlled Trials Register, or relevant original studies and review articles were approached for additional studies or details of all relevant studies. Results Morning peak expiratory flow（PEF） ,evening PEF and clinic FEV1 were 17.59L/rain, 14.95L/min and 0.08L/min higher with combination therpy than with increasing ICSs by two fold or more at endpoint,respeetively. The risk of asthmatic exacerbation was reduced in tile combination therpy group compared with the increased doses of ICS groups,with OR being 0.61 （95% CI 0.53 -0.70,P 〈0.01 ）. Significantly increases in tile percent of symptom-free days 6.30 （95 % CI 3.52 - 9.10 ）. aslhma-cantrol days 9.49 （ 95% CI 4.74 - 14.25） and relieve-free days 6.59（95% CI 6.10 - 7.08） were observed in patients treated with ICS/LABA compared with increased doses of ICSs at endpoint. Reduction in reliever medication use （inhalations/day）0.22 （95% CI 0.11 - 0.33） with significant difference was also observe, d at endpoint. Conclusion Combination products of ]CS/LABA were more effective than a high dose of ICSs in improving lung function,reducing asthmatic exacerbation and use of reliever medication and improving control of asthma.