Jaeschke Roman, O'Byrne Paul M, Mejza Filip, Nair Parameswaran, Lesniak Wiktoria, Brozek Jan, Thabane Lehana, Cheng Ji, Schünemann Holger J, Sears Malcolm R, Guyatt Gordon
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Crit Care Med. 2008 Nov 15;178(10):1009-16. doi: 10.1164/rccm.200804-494OC. Epub 2008 Sep 5.
Inhaled long-acting beta-agonists (LABAs), when used as monotherapy in asthma, may increase asthma-related hospitalizations, life threatening events requiring intubation/mechanical ventilation, and asthma-related deaths, but concomitant use of inhaled corticosteroids (ICS) may modify this effect.
To determine the safety of long-acting beta-agonists among patients with asthma using corticosteroids.
We conducted a systematic review and metaanalysis of parallel-group, blinded, randomized, controlled trials with at least 12 weeks of treatment addressing the impact of LABA on asthma-related and total morbidity and mortality in patients concomitantly using ICS. We searched MEDLINE, EMBASE, ACPJC, and Cochrane (Central) databases, and contacted authors and sponsors.
We used a random effects model to pool results from different studies as odds ratios (ORs) (95% confidence interval [CI]) (OR < 1.0 favors LABA). The search yielded 62 relevant studies included in this analysis. Among over 29,000 participants (15,710 taking LABA, with over 8,000 patient-years observed in the LABA groups), there were three asthma-related deaths and two asthma-related, nonfatal intubations (all in LABA groups; <or= one event per study). Differences in asthma-related hospitalizations (OR, 0.74; 95% CI, 0.53-1.03) and asthma-related serious adverse events (mostly hospitalizations; OR, 0.75; 95% CI, 0.54-1.03) failed to reach statistical significance. The OR for total mortality was 1.26 (95% CI, 0.58-2.74), reflecting 14 deaths in LABA groups and eight deaths in control groups, respectively.
In patients with asthma using ICS, LABA did not increase the risk of asthma-related hospitalizations. There were very few asthma-related deaths and intubations, and events were too infrequent to establish LABA's relative effect on these outcomes.
吸入性长效β受体激动剂（LABA）在哮喘单药治疗时，可能会增加与哮喘相关的住院率、需要插管/机械通气的危及生命事件以及与哮喘相关的死亡，但同时使用吸入性糖皮质激素（ICS）可能会改变这种效应。
确定在使用糖皮质激素的哮喘患者中长效β受体激动剂的安全性。
我们对平行组、双盲、随机对照试验进行了系统评价和荟萃分析，这些试验治疗时间至少为12周，探讨了LABA对同时使用ICS的患者与哮喘相关的发病率和总发病率及死亡率的影响。我们检索了MEDLINE、EMBASE、ACPJC和Cochrane（Central）数据库，并联系了作者和赞助商。
我们使用随机效应模型汇总不同研究的结果，以比值比（OR）（95%置信区间[CI]）表示（OR<1.0有利于LABA）。检索得到62项相关研究纳入本分析。在超过29000名参与者中（15710名使用LABA，LABA组观察到超过8000患者年），有3例与哮喘相关的死亡和2例与哮喘相关的非致命性插管（均在LABA组；每项研究≤1例事件）。与哮喘相关的住院率差异（OR，0.74；95%CI，0.53 - 1.03）和与哮喘相关的严重不良事件（主要是住院；OR，0.75；95%CI，0.54 - 1.03）未达到统计学显著性。总死亡率的OR为1.26（95%CI，0.58 - 2.74），分别反映LABA组14例死亡和对照组8例死亡。
在使用ICS的哮喘患者中，LABA不会增加与哮喘相关的住院风险。与哮喘相关的死亡和插管极少，且事件发生频率过低，无法确定LABA对这些结局的相对影响。
