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慢性阻塞性肺疾病患者每日1次单吸入器三联疗法与二联疗法比较
Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD


David A. Lipson ... 呼吸系统疾病 • 2018.05.03
相关阅读
• 三联疗法是否有益于慢性阻塞性肺疾病患者 • 有症状的COPD患者可从三联疗法获益

慢性阻塞性肺疾病三联吸入治疗是否优于二联吸入治疗

 

周玉民,冉丕鑫*

广州医科大学附属第一医院呼吸疾病国家重点实验室;呼吸疾病国家临床研究中心

* 通讯作者

 

支气管扩张药物是慢性阻塞性肺疾病(慢阻肺)治疗的主要药物。2018《慢性阻塞性肺疾病全球倡议》(GOLD)推荐吸入长效毒蕈碱拮抗剂(LAMA)或吸入长效β2受体激动剂(LABA)支气管扩张剂作为初始维持治疗;如果疗效不佳,则推荐联合使用。对多症状且加重频繁的患者(D组),在联合应用LAMA-LABA或者吸入皮质类固醇(ICS)-LABA的基础上,如果症状持续或持续急性加重,GOLD建议三联吸入治疗(LAMA-LABA-ICS)。虽然有研究表明三联吸入治疗与二联治疗相比,对改善肺功能和缓解慢阻肺症状有阳性作用,但迄今为止它的使用还需要患者每日多次使用数次吸入器;而且由于长期吸入ICS增加部分患者的肺炎风险,二联吸入治疗(LAMA-LABA)的基础上加用ICS的三联长期吸入治疗还存在争议1

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摘要


背景

慢性阻塞性肺疾病(COPD)治疗中吸入型糖皮质激素、长效毒蕈碱拮抗剂(LAMA)、长效β2受体激动剂(LABA)三联疗法与二联疗法(吸入型糖皮质激素-LABA或LAMA-LABA)相比的益处尚不确定。

 

方法

在该随机临床试验纳入的10,355例COPD患者中,我们比较了52周每日1次糠酸氟替卡松(一种吸入型糖皮质激素)100 μg、芜地溴铵(一种LAMA)62.5 μg、维兰特罗(一种LABA)25μg联合用药(三联疗法)与糠酸氟替卡松-维兰特罗(剂量分别为100 μg和25 μg)、芜地溴铵-维兰特罗(剂量分别为62.5 μg和25 μg)联合用药。每种方案均通过单一Ellipta吸入器给药。研究主要结局为治疗期间中或重度COPD加重的年发生率。

 

结果

三联疗法组COPD中或重度加重的发生率为每年0.91次,糠酸氟替卡松-维兰特罗组为每年1.07次(三联疗法的率比,0.85;95%置信区间[CI],0.80~0.90;15%差异;P<0.001),芜地溴铵-维兰特罗组为每年1.21次(三联疗法的率比,0.75;95% CI,0.70~0.81;25%差异;P<0.001)。三联疗法组导致住院的重度COPD加重的发生率为每年0.13次,而在芜地溴铵-维兰特组为0.19次(率比,0.66;95% CI,0.56~0.78;34%差异;P<0.001)。吸入型糖皮质激素组的肺炎发生率高于芜地溴铵-维兰特罗组,根据至首次事件发生时间分析,三联疗法组中临床医师诊断肺炎的风险显著高于芜地溴铵-维兰特罗组(风险比,1.53;95% CI,1.22~1.92;P<0.001)。

 

结论

该人群中糠酸氟替卡松、芜地溴铵、维兰特罗三联疗法与糠酸氟替卡松-芜地溴铵或芜地溴铵-维兰特罗相比,中或重度COPD加重的发生率较低。三联疗法与芜地溴铵-维兰特罗相比COPD所致住院率也较低(由葛兰素史克公司资助;IMPACT在ClinicalTrials.gov注册号为NCT02164513)。





作者信息

David A. Lipson, M.D., Frank Barnhart, D.V.M., Noushin Brealey, M.D., Jean Brooks, M.Sc., Gerard J. Criner, M.D., Nicola C. Day, Ph.D., Mark T. Dransfield, M.D., David M.G. Halpin, M.D., MeiLan K. Han, M.D., C. Elaine Jones, Ph.D., Sally Kilbride, M.Sc., Peter Lange, M.D., David A. Lomas, M.D., Ph.D., Fernando J. Martinez, M.D., Dave Singh, M.D., Maggie Tabberer, M.Sc., Robert A. Wise, M.D., and Steven J. Pascoe, M.B., B.S. for the IMPACT Investigators
From GlaxoSmithKline, Collegeville (D.A. Lipson, J.B., S.J.P.), and the Perelman School of Medicine, University of Pennsylvania (D.A. Lipson), and Lewis Katz School of Medicine at Temple University (G.J.C.), Philadelphia — all in Pennsylvania; GlaxoSmithKline, Research Triangle Park, NC (F.B., C.E.J.); GlaxoSmithKline, Stockley Park West, Uxbridge (N.B., N.C.D., S.K., M.T.), the Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter (D.M.G.H.), UCL Respiratory, University College London, London (D.A. Lomas), and the Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester University NHS Foundation Trust, Manchester (D.S.) — all in the United Kingdom; the Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham (M.T.D.); the Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor (M.K.H.); the Department of Public Health, University of Copenhagen, Copenhagen (P.L.), and the Medical Department, Pulmonary Section, Herlev–Gentofte Hospital, Herlev (P.L.) — both in Denmark; New York–Presbyterian Hospital/Weill Cornell Medical Center, New York (F.J.M.); and the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (R.A.W.). Address reprint requests to Dr. Lipson at GlaxoSmithKline, 1250 S. Collegeville Rd., Collegeville, PA 19426, or at david.a.lipson@gsk.com.

 

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