Ducharme Francine M, Lasserson Toby J, Cates Christopher J
Research Centre, CHU Sainte-Justine and the Department of Pediatrics, University of Montreal, Room number 7939, 3175 Cote Sainte-Catherine, Montreal, Québec, Canada, H3T 1C5.
Cochrane Database Syst Rev. 2011 May 11(5):CD003137. doi: 10.1002/14651858.CD003137.pub4.
Asthma patients who continue to experience symptoms despite being on regular inhaled corticosteroids (ICS) represent a management challenge. Long-acting beta(2)-agonists (LABA) or anti-leukotrienes (LTRA) are two treatment options that could be considered as add-on therapy to ICS.
We compared the efficacy and safety profile of adding either daily LABA or LTRA in adults and children with asthma who remain symptomatic on ICS.
We searched the Cochrane Airways Group Specialised Register (up to and including March 2010). We consulted reference lists of all included studies and contacted authors and pharmaceutical manufacturers for other published or unpublished studies.
We included randomised controlled trials (RCTs) conducted in adults or children with recurrent asthma that was treated with ICS and where a fixed dose of a long-acting beta(2)-agonist or leukotriene agent was added for a minimum of 28 days.
Two authors independently assessed the risk of bias of included studies and extracted data. We sought unpublished data and further details of study design, where necessary.
We included 17 RCTs (7032 participants), of which 16 recruited adults and adolescents (6850) and one recruited children aged 6 to 17 years (182). Participants demonstrated substantial reversibility to short-acting beta-agonist at baseline. The studies were at a low risk of bias. The risk of exacerbations requiring systemic corticosteroids was lower with the combination of LABA and ICS compared with LTRA and ICS, from 11% to 9% (RR 0.83, 95% CI 0.71 to 0.97; six studies, 5571 adults). The number needed to treat (NNT) with LABA compared to LTRA to prevent one exacerbation over 48 weeks was 38 (95% CI 22 to 244). The choice of LTRA did not significantly affect the results. The effect appeared stronger in the trials using a single device to administer ICS and LABA compared to those using two devices. In the absence of data from the paediatric trial and the clinical homogeneity of studies, we could not perform subgroup analyses. The addition to ICS of LABA compared to LTRA was associated with a statistically greater improvement from baseline in several of the secondary outcomes, including lung function, functional status measures and quality of life. Serious adverse events were more common with LABA than LTRA, although the estimate was imprecise (RR 1.35, 95% CI 1.00 to 1.82), and the NNT to harm for one additional patient to suffer a serious adverse event on LABA over 48 weeks was 78 (95% CI 33 to infinity). The risk of withdrawal for any reason in adults was significantly lower with LABA and ICS compared to LTRA and ICS (RR 0.84, 95% CI 0.74 to 0.96).
AUTHORS' CONCLUSIONS: In adults with asthma that is inadequately controlled on low doses of inhaled steroids and showing significant reversibility with beta(2)-agonists, LABA is superior to LTRA in reducing oral steroid treated exacerbations. Differences favouring LABA in lung function, functional status and quality of life scores are generally modest. There is some evidence of increased risk of SAEs with LABA. The findings support the use of a single inhaler for the delivery of LABA and inhaled corticosteroids. We are unable to draw conclusions about which treatment is better as add-on therapy for children.
尽管规律使用吸入性糖皮质激素（ICS），但仍有症状的哮喘患者面临管理挑战。长效β2受体激动剂（LABA）或抗白三烯药物（LTRA）是可考虑作为ICS附加治疗的两种选择。
我们比较了在使用ICS后仍有症状的成人和儿童哮喘患者中添加每日LABA或LTRA的疗效和安全性。
我们检索了Cochrane气道组专业注册库（截至2010年3月，包括该月）。我们查阅了所有纳入研究的参考文献列表，并联系作者和制药商以获取其他已发表或未发表的研究。
我们纳入了在成人或复发性哮喘儿童中进行的随机对照试验（RCT），这些患者接受ICS治疗，并添加固定剂量的长效β2受体激动剂或白三烯药物至少28天。
两位作者独立评估纳入研究的偏倚风险并提取数据。必要时，我们寻求未发表的数据和研究设计的进一步细节。
我们纳入了17项RCT（7032名参与者），其中16项招募了成人和青少年（6850名），1项招募了6至17岁的儿童（182名）。参与者在基线时对短效β受体激动剂表现出显著的可逆性。这些研究的偏倚风险较低。与LTRA加ICS相比，LABA加ICS使需要全身使用糖皮质激素的加重发作风险更低，从11%降至9%（风险比0.83，95%置信区间0.71至0.97；6项研究，5571名成人）。与LTRA相比，使用LABA预防48周内一次加重发作的治疗所需人数（NNT）为38（95%置信区间22至244）。LTRA的选择对结果没有显著影响。与使用两种装置的试验相比，在使用单一装置给予ICS和LABA的试验中，效果似乎更强。由于缺乏儿科试验数据以及研究的临床同质性，我们无法进行亚组分析。与LTRA相比，LABA添加到ICS中在几个次要结局方面与基线相比有统计学上更大的改善，包括肺功能、功能状态测量和生活质量。严重不良事件在LABA组比LTRA组更常见，尽管估计不精确（风险比1.35，95%置信区间1.00至1.82），在48周内LABA组导致一名额外患者发生严重不良事件的伤害所需人数为78（95%置信区间33至无穷大）。与LTRA加ICS相比，LABA加ICS在成人中因任何原因退出治疗的风险显著更低（风险比0.84，95%置信区间0.74至0.96）。
在低剂量吸入性糖皮质激素控制不佳且对β2受体激动剂有显著可逆性的成人哮喘患者中，LABA在减少口服糖皮质激素治疗的加重发作方面优于LTRA。在肺功能、功能状态和生活质量评分方面有利于LABA的差异通常较小。有一些证据表明LABA导致严重不良事件的风险增加。这些发现支持使用单一吸入器来递送LABA和吸入性糖皮质激素。我们无法得出哪种治疗作为儿童附加治疗更好的结论。
