Goyal Vikas, Chang Anne B
Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Australia.
Cochrane Database Syst Rev. 2014 Jun 10;2014(6):CD010327. doi: 10.1002/14651858.CD010327.pub2.
Bronchiectasis is a major contributor to chronic respiratory morbidity and mortality worldwide. Wheeze and other asthma-like symptoms and bronchial hyperreactivity may occur in people with bronchiectasis. Physicians often use asthma treatments in patients with bronchiectasis.
To assess the effects of inhaled long-acting beta2-agonists (LABA) combined with inhaled corticosteroids (ICS) in children and adults with bronchiectasis during (1) acute exacerbations and (2) stable state.
The Cochrane Airways Group searched the the Cochrane Airways Group Specialised Register of Trials, which includes records identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other databases. The Cochrane Airways Group performed the latest searches in October 2013.
All randomised controlled trials (RCTs) of combined ICS and LABA compared with a control (placebo, no treatment, ICS as monotherapy) in children and adults with bronchiectasis not related to cystic fibrosis (CF).
Two review authors extracted data independently using standard methodological procedures as expected by The Cochrane Collaboration.
We found no RCTs comparing ICS and LABA combination with either placebo or usual care. We included one RCT that compared combined ICS and LABA with high-dose ICS in 40 adults with non-CF bronchiectasis without co-existent asthma. All participants received three months of high-dose budesonide dipropionate treatment (1600 micrograms). After three months, participants were randomly assigned to receive either high-dose budesonide dipropionate (1600 micrograms per day) or a combination of budesonide with formoterol (640 micrograms of budesonide and 18 micrograms of formoterol) for three months. The study was not blinded. We assessed it to be an RCT with overall high risk of bias. Data analysed in this review showed that those who received combined ICS-LABA (in stable state) had a significantly better transition dyspnoea index (mean difference (MD) 1.29, 95% confidence interval (CI) 0.40 to 2.18) and cough-free days (MD 12.30, 95% CI 2.38 to 22.2) compared with those receiving ICS after three months of treatment. No significant difference was noted between groups in quality of life (MD -4.57, 95% CI -12.38 to 3.24), number of hospitalisations (odds ratio (OR) 0.26, 95% CI 0.02 to 2.79) or lung function (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Investigators reported 37 adverse events in the ICS group versus 12 events in the ICS-LABA group but did not mention the number of individuals experiencing adverse events. Hence differences between groups were not included in the analyses. We assessed the overall evidence to be low quality.
AUTHORS' CONCLUSIONS: In adults with bronchiectasis without co-existent asthma, during stable state, a small single trial with a high risk of bias suggests that combined ICS-LABA may improve dyspnoea and increase cough-free days in comparison with high-dose ICS. No data are provided for or against, the use of combined ICS-LABA in adults with bronchiectasis during an acute exacerbation, or in children with bronchiectasis in a stable or acute state. The absence of high quality evidence means that decisions to use or discontinue combined ICS-LABA in people with bronchiectasis may need to take account of the presence or absence of co-existing airway hyper-responsiveness and consideration of adverse events associated with combined ICS-LABA.
支气管扩张是全球慢性呼吸道疾病发病率和死亡率的主要促成因素。支气管扩张患者可能出现喘息及其他类似哮喘的症状和支气管高反应性。医生常对支气管扩张患者使用哮喘治疗方法。
评估吸入长效β2受体激动剂(LABA)联合吸入性糖皮质激素(ICS)对支气管扩张患儿及成人在(1)急性加重期和(2)稳定期的治疗效果。
Cochrane气道组检索了Cochrane气道组专业试验注册库,其中包括从Cochrane对照试验中央注册库(CENTRAL)、MEDLINE、EMBASE及其他数据库中识别出的记录。Cochrane气道组于2013年10月进行了最新检索。
所有将ICS与LABA联合使用并与对照组(安慰剂、不治疗、ICS单药治疗)进行比较的随机对照试验(RCT),试验对象为非囊性纤维化(CF)相关性支气管扩张的儿童及成人。
两名综述作者按照Cochrane协作网预期的标准方法程序独立提取数据。
我们未找到将ICS与LABA联合使用并与安慰剂或常规治疗进行比较的RCT。我们纳入了一项RCT,该试验将ICS与LABA联合使用与高剂量ICS进行比较,试验对象为40名无合并哮喘的非CF支气管扩张成人。所有参与者均接受了为期三个月的高剂量二丙酸倍氯米松治疗(1600微克)。三个月后,参与者被随机分配接受高剂量二丙酸倍氯米松(每日1600微克)或布地奈德与福莫特罗联合用药(640微克布地奈德和18微克福莫特罗),为期三个月。该研究未设盲。我们评估其为一项总体偏倚风险较高的RCT。本综述分析的数据显示,在治疗三个月后,接受ICS与LABA联合治疗(稳定期)的患者在过渡性呼吸困难指数方面显著更好(平均差(MD)1.29,95%置信区间(CI)0.40至2.18),且无咳嗽天数更多(MD 12.30,95%CI 2.38至22.2)。两组在生活质量(MD -4.57,95%CI -12.38至3.24)、住院次数(比值比(OR)0.26,95%CI 0.02至2.79)或肺功能(一秒用力呼气容积(FEV1)和用力肺活量(FVC))方面未观察到显著差异。研究者报告ICS组有37例不良事件,ICS与LABA联合治疗组有12例不良事件,但未提及发生不良事件的个体数量。因此,组间差异未纳入分析。我们评估总体证据质量较低。
在无合并哮喘的支气管扩张成人患者的稳定期,一项偏倚风险较高的小型单中心试验表明,与高剂量ICS相比,ICS与LABA联合使用可能改善呼吸困难并增加无咳嗽天数。对于支气管扩张成人患者在急性加重期或支气管扩张患儿在稳定期或急性加重期使用ICS与LABA联合治疗,未提供支持或反对的数据。缺乏高质量证据意味着在支气管扩张患者中决定使用或停用ICS与LABA联合治疗可能需要考虑是否存在合并的气道高反应性以及与ICS与LABA联合治疗相关的不良事件。