Combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) inhaler therapy (ICS/LABA therapy) represents the mainstay of the management of moderate and severe asthma, recommended in the Global Initiative for Asthma (GINA) guidelines for steps 3, 4 and 5 [1]. Indeed, in some countries, such as Australia, ICS/LABA therapy now represents the default ICS treatment, with a recent survey reporting that just over four out of every five adults with asthma who are prescribed ICS receive ICS/LABA therapy [2, 3]. As a result, the optimal use of ICS/LABA therapy is a priority in the management of asthma and this requires the consideration of a number of key issues. First, ICS and LABA should not be prescribed as separate inhalers in asthma due to the risks associated with LABA monotherapy in patients who are non-adherent with their ICS inhaler [4]. This recommendation reflects concern that LABA monotherapy increases the risk of mortality in patients with poorly controlled asthma, in contrast to ICS/LABA treatment for which no such risk has been identified [5]. Secondly, there are two main management regimens by which ICS/LABA inhalers can be prescribed. The most common “standard” regimen is fixed-dose ICS/LABA maintenance with a short-acting β-agonist (SABA) as reliever. The alternative option is to use a combination ICS/LABA inhaler as both maintenance and reliever therapy (referred to as the MART regimen). To implement the MART regimen it is necessary for the LABA component to have a fast onset of action, which allows for its use as a reliever as well as a maintenance therapy. The efficacy of the MART regimen has been illustrated with budesonide/formoterol using both turbuhaler [6] and metered dose inhaler (MDI) [7] devices for delivery, as well as with beclometasone/formoterol using the MDI device [8]. Thirdly, there is evidence that turbuhaler administration of budesonide/formoterol according to the MART regimen is more effective than the regimen comprising fixed-dose ICS/LABA maintenance (at a higher maintenance ICS dose) with “as required” SABA therapy in adults and children with chronic asthma [9]. In the Cochrane systematic review and meta-analysis summarising this evidence, the point estimates for the magnitude of the greater efficacy of the MART regimen were large. For the MART regimen versus the higher fixed-dose ICS/LABA regimen, the odds ratio for risk of exacerbations requiring hospitalisation or a visit to the emergency room was 0.72 (95% CI 0.57–0.90) while the odds ratio for exacerbations requiring oral corticosteroids was 0.75 (95% CI 0.65–0.87). This knowledge-base has now been extended by the publication, by jorup et al. [10] in this issue of the European Respiratory Journal, of an individual patient data subgroup meta-analysis which reports on the efficacy of the MART regimen in children aged 12–17 years. This meta-analysis includes 1847 adolescents from six double-blind randomised controlled trials comparing MART with an active comparator. Five trials required patients to have had at least one asthma exacerbation in the previous year at randomisation, thereby ensuring that the findings could be generalised to high risk adolescents with asthma. Comparator treatments used a SABA or LABA as the reliever therapy and included maintenance ICS at a dose of at least double the equivalent daily maintenance dose of ICS used in the MART regimen, or maintenance ICS/LABA at the same or a higher equivalent daily maintenance ICS dose, thereby representing the main treatment options from GINA steps 2, 3, 4 and 5 [1]. ICS/LABA maintenance and reliever therapy is recommended for adolescents with asthma at risk of severe exacerbations http://ow.ly/xhhO30gKZ6W

中文翻译：

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吸入性皮质类固醇/长效β-激动剂维持和缓解治疗方案：从何而来？

联合吸入性皮质类固醇 (ICS)/长效 β-激动剂 (LABA) 吸入疗法（ICS/LABA 疗法）代表中度和重度哮喘管理的主要支柱，在全球哮喘倡议 (GINA) 指南中推荐用于步骤 3 , 4 和 5 [1]。事实上，在澳大利亚等一些国家，ICS/LABA 治疗现在代表了默认的 ICS 治疗，最近的一项调查报告称，每 5 名接受 ICS 处方的哮喘成人中，有超过 4 人接受 ICS/LABA 治疗 [2, 3 ]。因此，ICS/LABA 治疗的最佳使用是哮喘管理的优先事项，这需要考虑许多关键问题。首先，由于不依从 ICS 吸入器的患者与 LABA 单药治疗相关的风险，ICS 和 LABA 不应作为单独的哮喘吸入器开处方 [4]。该建议反映了这样一种担忧，即 LABA 单药治疗会增加哮喘控制不佳患者的死亡风险，而 ICS/LABA 治疗则没有发现此类风险[5]。其次，ICS/LABA 吸入器有两种主要的管理方案。最常见的“标准”方案是固定剂量 ICS/LABA 维持治疗，并使用短效 β-激动剂 (SABA) 作为缓解剂。另一种选择是使用联合 ICS/LABA 吸入器作为维持和缓解治疗（称为 MART 方案）。为了实施 MART 方案，LABA 成分必须具有快速起效，这允许其用作缓解剂和维持疗法。MART 方案的疗效已通过使用涡轮吸入器 [6] 和计量吸入器 (MDI) [7] 装置进行递送的布地奈德/福莫特罗以及使用 MDI 装置 [8] 的倍氯米松/福莫特罗进行说明。第三，有证据表明，在成人和儿童中，根据 MA​​RT 方案，布地奈德/福莫特罗 turbuhaler 给药比包含固定剂量 ICS/LABA 维持（更高的 ICS 维持剂量）和“按需”SABA 治疗的方案更有效慢性哮喘[9]。在总结这一证据的 Cochrane 系统评价和荟萃分析中，对 MART 方案更大疗效的幅度的点估计很大。对于 MART 方案与较高固定剂量 ICS/LABA 方案相比，需要住院或去急诊室就诊的急性加重风险的优势比为 0.72 (95% CI 0.57–0.90)，而需要口服皮质类固醇的急性加重的优势比为 0.75 (95% CI 0.65–0.87)。该知识库现已通过 jorup 等人的出版物进行了扩展。[10] 在本期《欧洲呼吸杂志》中，一项个体患者数据亚组荟萃分析报告了 MART 方案对 12-17 岁儿童的疗效。这项荟萃分析包括来自六项双盲随机对照试验的 1847 名青少年，这些试验将 MART 与活性对照试验进行了比较。五项试验要求患者在随机分组时在前一年至少发生过一次哮喘急性发作，从而确保研究结果可以推广到患有哮喘的高危青少年。比较治疗使用 SABA 或 LABA 作为缓解治疗，包括维持 ICS 的剂量至少是 MART 方案中使用的 ICS 的等效每日维持剂量的两倍，或维持 ICS/LABA 的剂量与每日维持 ICS 相同或更高剂量，从而代表 GINA 步骤 2、3、4 和 5 [1] 中的主要治疗方案。ICS/LABA 维持和缓解治疗推荐用于有严重恶化风险的哮喘青少年 http://ow.ly/xhhO30gKZ6W