Johnstone Kate J, Chang Anne B, Fong Kwun M, Bowman Rayleen V, Yang Ian A
School of Medicine, The University of Queensland, Brisbane, Australia.
Cochrane Database Syst Rev. 2013 Mar 28;2013(3):CD009305. doi: 10.1002/14651858.CD009305.pub2.
Persistent cough is a common clinical problem. Despite thorough investigation and empirical management, a considerable proportion of those people with subacute and chronic cough have unexplained cough, for which treatment options are limited. While current guidelines recommend inhaled corticosteroids (ICS), the research evidence for this intervention is conflicting.
To assess the effects of ICS for subacute and chronic cough in adults.
We searched the Cochrane Airways Group Register of Trials, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and ClinicalTrials.gov in December 2012 and conducted handsearches.
Two authors independently assessed all potentially relevant trials. All published and unpublished randomised comparisons of ICS versus placebo in adults with subacute or chronic cough were included. Participants with known chronic respiratory disease and asthma were excluded. Studies of cough-variant asthma and eosinophilic bronchitis were eligible.
Two authors independently extracted data pertaining to pre-defined outcomes. The primary outcome was the proportion of participants with clinical cure or significant improvement (over 70% reduction in cough severity measure) at follow up (clinical success). The secondary outcomes included proportion of participants with clinical cure or over 50% reduction in cough severity measure at follow up, mean change in cough severity measures, complications of cough, biomarkers of inflammation and adverse effects. We requested additional data from study authors.
Eight primary studies, including 570 participants, were included. The overall methodological quality of studies was good. Significant clinical heterogeneity resulting from differences in participants and interventions, as well as variation in outcome measures, limited the validity of comparisons between studies for most outcomes. Data for the primary outcome of clinical cure or significant (> 70%) improvement were available for only three studies, which were too heterogeneous to pool. Similarly, heterogeneity in study characteristics limited the validity of meta-analysis for the secondary outcomes of proportion of participants with clinical cure or over 50% reduction in cough severity measure and clinical cure. One parallel group trial of predominantly chronic cough with 'cough-variant asthma' identified a significant treatment effect and contributed to the majority of statistical heterogeneity for these outcomes. While ICS treatment resulted in a mean decrease in cough score of 0.34 standard deviations (SMD -0.34; 95% CI -0.56 to -0.13; 346 participants), the quality of evidence was low. Heterogeneity also prevented meta-analysis for the outcome of mean change in visual analogue scale score. Meta-analysis was not possible for the outcomes of pulmonary function, complications of cough or biomarkers of inflammation due to insufficient data. There was moderate quality evidence that treatment with ICS did not significantly increase the odds of experiencing an adverse event (OR 1.67; 95% CI 0.92 to 3.04).
AUTHORS' CONCLUSIONS: The studies were highly heterogeneous and results were inconsistent. Heterogeneity in study design needs to be addressed in future research in order to test the efficacy of this intervention. International cough guidelines recommend that a trial of ICS should only be considered in patients after thorough evaluation including chest X-ray and consideration of spirometry and other appropriate investigations.
持续性咳嗽是常见的临床问题。尽管进行了全面检查和经验性治疗,但相当一部分亚急性和慢性咳嗽患者的咳嗽原因不明,且治疗选择有限。虽然当前指南推荐吸入性糖皮质激素(ICS),但该干预措施的研究证据存在矛盾。
评估ICS对成人亚急性和慢性咳嗽的疗效。
我们于2012年12月检索了Cochrane Airways试验组注册库、Cochrane对照试验中央注册库、MEDLINE、EMBASE和ClinicalTrials.gov,并进行了手工检索。
两位作者独立评估所有可能相关的试验。纳入所有已发表和未发表的关于ICS与安慰剂在成人亚急性或慢性咳嗽患者中的随机对照比较。排除已知患有慢性呼吸道疾病和哮喘的参与者。咳嗽变异性哮喘和嗜酸性粒细胞性支气管炎的研究符合条件。
两位作者独立提取与预定义结局相关的数据。主要结局是随访时临床治愈或显著改善(咳嗽严重程度测量值降低超过70%)的参与者比例(临床成功)。次要结局包括随访时临床治愈或咳嗽严重程度测量值降低超过50%的参与者比例、咳嗽严重程度测量值的平均变化、咳嗽并发症、炎症生物标志物和不良反应。我们向研究作者索要了额外数据。
纳入了8项主要研究,共570名参与者。研究的总体方法学质量良好。参与者和干预措施的差异以及结局测量的变化导致的显著临床异质性,限制了大多数结局研究间比较的有效性。仅有3项研究提供了临床治愈或显著(>70%)改善这一主要结局的数据,这些数据异质性太大,无法合并。同样,研究特征的异质性限制了对临床治愈或咳嗽严重程度测量值降低超过50%的参与者比例以及临床治愈这些次要结局进行荟萃分析的有效性。一项主要针对“咳嗽变异性哮喘”的慢性咳嗽的平行组试验确定了显著的治疗效果,并导致了这些结局的大部分统计异质性。虽然ICS治疗使咳嗽评分平均降低了0.34个标准差(标准化均数差-0.34;95%置信区间-0.56至-0.13;346名参与者),但证据质量较低。异质性也妨碍了对视觉模拟量表评分平均变化结局进行荟萃分析。由于数据不足,无法对肺功能、咳嗽并发症或炎症生物标志物结局进行荟萃分析。有中等质量的证据表明,ICS治疗不会显著增加发生不良事件的几率(比值比1.67;95%置信区间0.92至3.04)。
这些研究高度异质性,结果不一致。未来研究需要解决研究设计中的异质性问题,以检验该干预措施的疗效。国际咳嗽指南建议,只有在对患者进行包括胸部X线检查并考虑肺功能测定和其他适当检查的全面评估后,才应考虑进行ICS试验。