Lasserson Toby J, Ferrara Giovanni, Casali Lucio
Cochrane Editorial Unit, The Cochrane Collaboration, 13 Cavendish Square, London, UK, W1G 0AN.
Cochrane Database Syst Rev. 2011 Dec 7;2011(12):CD004106. doi: 10.1002/14651858.CD004106.pub4.
Long-acting beta-agonists are a common second line treatment in people with asthma inadequately controlled with inhaled corticosteroids. Single device inhalers combine a long-acting beta-agonist with an inhaled steroid delivering both drugs as a maintenance treatment regimen. This updated review compares two fixed-dose options, fluticasone/salmeterol FP/SALand budesonide/formoterol, since this comparison represents a common therapeutic choice.
To assess the relative effects of fluticasone/salmeterol and budesonide/formoterol in people with asthma.
We searched the Cochrane Airways Group register of trials with prespecified terms. We performed additional hand searching of manufacturers' web sites and online trial registries. Search results are current to June 2011.
We included randomised studies comparing fixed dose fluticasone/salmeterol and budesonide/formoterol in adults or children with a diagnosis of asthma. Treatment in the studies had to last for a minimum of 12 weeks.
Two authors independently assessed studies for inclusion in the review. We combined continuous data outcomes with a mean difference (MD), and dichotomous data outcomes with an odds ratio (OR). We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
Five studies met the review entry criteria (5537 adults). Study populations entered the studies having previously been treated with inhaled steroids and had moderate or mild airway obstruction (mean FEV(1) predicted between 65% and 84% at baseline). Most of the studies assessed treatment over a period of six months. The studies were at a low risk of selection and performance/detection bias, although we could not determine whether missing data had an impact on the results. Availablility of outcome data was satisfactory.Primary outcomesThe odds ratio for exacerbations requiring oral steroids was lower with fluticasone/salmeterol but did not reach statistical significance (OR 0.89, 95% confidence interval (CI) 0.74 to 1.07, four studies, N = 4949). With an assumed risk with budesonide/formoterol of 106/1000 participants requiring oral steroids, treatment with fluticasone/salmeterol would lead to between 25 fewer and seven more people per 1000 experiencing a course of oral steroids. Although the odds of hospital admission was higher with fluticasone/salmeterol, this did not reach statistical significance (OR 1.29, 95% CI 0.68 to 2.47, four studies, 4879 participants). With an assumed risk in the budesonide/formoterol of 7/1000, between two fewer and 10 more people per 1000 would be hospitalised on fluticasone/salmeterol. The odds of a serious adverse event related to asthma was higher with fluticasone/salmeterol but did not differ significantly between treatments (OR 1.47, 95% CI 0.75 to 2.86, three studies, 4054 participants). With an assumed risk in the budesonide/formoterol of 7/1000, between two fewer and 13 more people per 1000 would experience a serious adverse event on fluticasone/salmeterol.Secondary outcomesLung function outcomes, symptoms, rescue medication, composite of exacerbations leading to either emergency department visit or hospital admission, withdrawals and adverse events did not differ statistically between treatments. Assessment of quality of life was limited to two studies, both of which gave results that did not reach statistical significance. One study reported one death out of 1000 participants on fluticasone/salmeterol and no deaths in a similar number of participants treated with budesonide/formoterol. No deaths were reported in the other studies.
AUTHORS' CONCLUSIONS: Statistical imprecision in the effect estimates for exacerbations and serious adverse events do not enable us to conclude that either therapy is superior. The uncertainty around the effect estimates justify further trials to provide more definitive conclusions; the overall quality of evidence based on GRADE recommendations for the three primary outcomes and withdrawals due to serious adverse events was moderate. We rated the quality of evidence for mortality to be low. Results for lung function outcomes showed that the drugs were sufficiently similar that further research is unlikely to change the effects. No trials were identified in the under-12s and research in this population is a high priority. Evaluation of quality of life is a priority for future research.
长效β受体激动剂是吸入性糖皮质激素治疗控制不佳的哮喘患者常用的二线治疗药物。单装置吸入器将长效β受体激动剂与吸入性糖皮质激素结合，作为维持治疗方案同时递送两种药物。本更新综述比较了两种固定剂量组合，氟替卡松/沙美特罗（FP/SAL）和布地奈德/福莫特罗，因为这种比较代表了一种常见的治疗选择。
评估氟替卡松/沙美特罗和布地奈德/福莫特罗对哮喘患者的相对疗效。
我们使用预先设定的检索词检索Cochrane Airways Group试验注册库。我们还对制造商网站和在线试验注册库进行了额外的手工检索。检索结果截至2011年6月。
我们纳入了比较固定剂量氟替卡松/沙美特罗和布地奈德/福莫特罗在诊断为哮喘的成人或儿童中的随机研究。研究中的治疗必须持续至少12周。
两位作者独立评估纳入综述的研究。我们将连续数据结果合并为平均差（MD），将二分数据结果合并为比值比（OR）。我们使用推荐分级评估、制定与评价（GRADE）系统评估证据质量。
五项研究符合综述纳入标准（5537名成人）。研究人群在进入研究前曾接受吸入性糖皮质激素治疗，且有中度或轻度气道阻塞（基线时预计平均FEV(1)在65%至84%之间）。大多数研究评估了六个月期间的治疗。这些研究存在低选择风险和执行/检测偏倚，尽管我们无法确定缺失数据是否对结果有影响。结局数据的可用性令人满意。
需要口服糖皮质激素的加重发作的比值比在氟替卡松/沙美特罗组较低，但未达到统计学显著性（OR 0.89，95%置信区间（CI）0.74至1.07，四项研究，N = 4949）。假设布地奈德/福莫特罗组有106/1000名参与者需要口服糖皮质激素，使用氟替卡松/沙美特罗治疗每1000人中经历口服糖皮质激素疗程的人数将减少25人至增加7人。尽管氟替卡松/沙美特罗组住院几率较高，但未达到统计学显著性（OR 1.29，95% CI 0.68至2.47，四项研究，4879名参与者）。假设布地奈德/福莫特罗组有7/1000的住院风险，使用氟替卡松/沙美特罗治疗每1000人中住院人数将减少2人至增加10人。与哮喘相关的严重不良事件的比值比在氟替卡松/沙美特罗组较高，但治疗组之间无显著差异（OR 1.47，95% CI 0.75至2.86，三项研究，4054名参与者）。假设布地奈德/福莫特罗组有7/1000的风险，使用氟替卡松/沙美特罗治疗每1000人中经历严重不良事件的人数将减少2人至增加13人。
肺功能结局、症状、急救药物、导致急诊就诊或住院的加重发作综合情况、退出研究情况和不良事件在治疗组之间无统计学差异。生活质量评估仅限于两项研究，两项研究结果均未达到统计学显著性。一项研究报告在使用氟替卡松/沙美特罗治疗的1000名参与者中有1例死亡，在接受布地奈德/福莫特罗治疗的类似数量参与者中无死亡报告。其他研究未报告死亡情况。
加重发作和严重不良事件效应估计的统计不精确性使我们无法得出哪种治疗更优的结论。效应估计的不确定性证明有必要进行进一步试验以得出更明确的结论；基于GRADE推荐的三项主要结局和因严重不良事件退出研究情况的证据总体质量为中等。我们将死亡率的证据质量评为低。肺功能结局结果表明两种药物足够相似，进一步研究不太可能改变疗效。未识别出12岁以下儿童的试验，该人群的研究是高度优先事项。生活质量评估是未来研究的优先事项。
