Kew Kayleigh M, Beggs Sean, Ahmad Shaleen
Population Health Research Institute, St George's, University of London, Cranmer Terrace, London, UK, SW17 0RE.
Cochrane Database Syst Rev. 2015 May 21;2015(5):CD011316. doi: 10.1002/14651858.CD011316.pub2.
Asthma is the most common chronic medical condition among children and is one of the most common causes of hospitalisation and medical visits. Poorly controlled asthma often leads to preventable exacerbations that require additional medications, hospital stays, or treatment in the emergency department.Long-acting beta2-agonists (LABA) are the preferred add-on treatment for children with asthma whose symptoms are not well controlled on inhaled corticosteroids (ICS). The US Food and Drug Administration has issued a 'black box' warning for LABA in asthma, and now recommends that they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved".
To compare the effect on asthma control and adverse effects of stepping down to inhaled corticosteroids (ICS)-only therapy versus continuing ICS plus LABA in children whose asthma is well controlled on combined ICS and LABA therapy.
We searched the Cochrane Airways Group Specialised Register, and also searched www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews, and manufacturers' trial registries (GlaxoSmithKline and AstraZeneca). We searched all databases from their inception to the present, and imposed no restriction on language of publication. The most recent search was done in April 2015.
We looked for parallel randomised controlled trials of at least eight weeks' duration, available as published full text, abstract only, or unpublished data. We excluded studies including participants with other chronic respiratory comorbidities (for example bronchiectasis).We looked for studies in which children (18 years or younger) whose asthma was well controlled on any dose of ICS and LABA combination therapy were randomised to: a) step-down therapy to ICS alone or b) continued use of ICS and LABA.We included any dose of LABA (formoterol, salmeterol, vilanterol) and any dose of ICS (beclomethasone, budesonide, ciclesonide, mometasone, flunisolide, fluticasone propionate, fluticasone furoate, triamcinolone) delivered in a combination inhaler or in separate inhalers.
Two review authors independently screened all records identified in the searches. We used a data extraction tool in Microsoft Excel to manage searches and document reasons for inclusion and exclusion, and to extract descriptive and numerical data from trials meeting the inclusion criteria.The prespecified primary outcomes were exacerbations requiring oral steroids, asthma control, and all-cause serious adverse events.
Despite conducting extensive searches of electronic databases, trial registries and manufacturers' websites we identified no trials matching the inclusion criteria.After removing duplicates, we screened 1031 abstracts, and assessed 43 full-text articles for inclusion. We identified several adult studies, which will be summarised in a separate review (Ahmad 2014). The most common reasons for exclusion after viewing full texts were 'wrong comparison' (n = 22) and 'adult population' (n = 18).Some adult studies recruited adolescents from age 15, but none reported data separately for those under 18.
AUTHORS' CONCLUSIONS: There is currently no evidence from randomised trials to inform the discontinuation of LABAs in children once asthma control is achieved with ICS plus LABA. It is disappointing that such an important issue has not been studied, and a randomised double-blind trial recruiting children who are controlled on ICS plus LABA is warranted. The study should be large enough to assess children of different ages, and to measure the important safety and efficacy outcomes suggested in this review over at least six months.The only randomised evidence for stopping LABA has been conducted in adults; it will be summarised in a separate review.
哮喘是儿童中最常见的慢性疾病，也是住院和就医的最常见原因之一。哮喘控制不佳常导致可预防的病情加重，需要额外用药、住院或在急诊科接受治疗。长效β2受体激动剂（LABA）是症状在吸入性糖皮质激素（ICS）治疗下控制不佳的哮喘儿童的首选附加治疗药物。美国食品药品监督管理局已对LABA用于哮喘治疗发布了“黑框”警告，现建议“在达到哮喘症状控制所需的最短时间内使用，一旦实现哮喘控制，尽可能停用”。
比较哮喘在ICS加LABA联合治疗下病情得到良好控制的儿童，降级至仅使用吸入性糖皮质激素（ICS）治疗与继续使用ICS加LABA治疗对哮喘控制的效果及不良反应。
我们检索了Cochrane气道组专业注册库，还检索了www.ClinicalTrials.gov、www.who.int/ictrp/en/、原始研究的参考文献列表和现有综述，以及制造商的试验注册库（葛兰素史克和阿斯利康）。我们检索了所有数据库自创建以来至目前的内容，且对出版物语言未作限制。最近一次检索于2015年4月进行。
我们寻找至少为期八周的平行随机对照试验，以已发表的全文、仅摘要或未发表的数据形式可得。我们排除了纳入患有其他慢性呼吸道合并症（如支气管扩张症）参与者的研究。我们寻找的研究中，哮喘在任何剂量的ICS和LABA联合治疗下病情得到良好控制的儿童（18岁及以下）被随机分为：a）降级至仅使用ICS治疗或b）继续使用ICS和LABA。我们纳入联合吸入器或单独吸入器中使用的任何剂量的LABA（福莫特罗、沙美特罗、维兰特罗）和任何剂量的ICS（倍氯米松、布地奈德、环索奈德、莫米松、氟尼缩松、丙酸氟替卡松、糠酸氟替卡松、曲安奈德）。
两位综述作者独立筛选检索中识别出的所有记录。我们使用Microsoft Excel中的数据提取工具来管理检索并记录纳入和排除的原因，以及从符合纳入标准的试验中提取描述性和数值数据。预先设定的主要结局为需要口服类固醇的病情加重、哮喘控制情况以及全因严重不良事件。
尽管对电子数据库、试验注册库和制造商网站进行了广泛检索，但我们未识别出符合纳入标准的试验。去除重复项后，我们筛选了1031篇摘要，并评估了43篇全文文章以确定是否纳入。我们识别出了几项成人研究，将在单独的综述中进行总结（艾哈迈德，2014年）。查看全文后排除的最常见原因是“比较错误”（n = 22）和“成人人群”（n = 18）。一些成人研究招募了15岁及以上的青少年，但没有一项研究分别报告18岁以下人群的数据。
目前尚无随机试验证据表明，哮喘在ICS加LABA治疗下实现控制后，儿童停用LABA的情况。如此重要的问题尚未得到研究令人失望，因此有必要开展一项针对在ICS加LABA治疗下病情得到控制的儿童的随机双盲试验。该研究应足够大，以评估不同年龄段的儿童，并在至少六个月内测量本综述中提出的重要安全性和有效性结局。关于停用LABA的唯一随机证据来自成人研究；将在单独的综述中进行总结。
