Edmonds Marcia L, Milan Stephen J, Camargo Carlos A, Pollack Charles V, Rowe Brian H
Schulich School of Medicine & Dentistry, London, Canada.
Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD002308. doi: 10.1002/14651858.CD002308.pub2.
Systemic corticosteroid therapy is central to the management of acute asthma. The use of inhaled corticosteroids (ICS) may also be beneficial in this setting.
To determine the benefit of ICS for the treatment of patients with acute asthma managed in the emergency department (ED).
We identified controlled clinical trials from the Cochrane Airways Group specialised register of controlled trials. Bibliographies from included studies, known reviews, and texts also were searched. The latest search was September 2012.
We included randomised controlled trials (RCTs) and quasi-RCTs. Studies were included if patients presented to the ED or its equivalent with acute asthma, and were treated with ICS or placebo, in addition to standard therapy. Two review authors independently selected potentially relevant articles, and then independently selected articles for inclusion. Methodological quality was independently assessed by two review authors. There were three different types of studies that were included in this review: 1) studies comparing ICS vs. placebo, with no systemic corticosteroids given to either treatment group, 2) studies comparing ICS vs. placebo, with systemic corticosteroids given to both treatment groups, and 3) studies comparing ICS alone versus systemic corticosteroids. For the analysis, the first two types of studies were included as separate subgroups in the primary analysis (ICS vs. placebo), while the third type of study was included in the secondary analysis (ICS vs. systemic corticosteroid).
Data were extracted independently by two review authors if the authors were unable to verify the validity of extracted information. Missing data were obtained from the authors or calculated from other data presented in the paper. Where appropriate, individual and pooled dichotomous outcomes were reported as odds ratios (OR) with 95% confidence intervals (CIs). Where appropriate, individual and pooled continuous outcomes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% CIs. The primary analysis employed a fixed-effect model and a random-effects model was used for sensitivity analysis. Heterogeneity is reported using I-squared (I(2)) statistics.
Twenty trials were selected for inclusion in the primary analysis (13 paediatric, seven adult), with a total number of 1403 patients. Patients treated with ICS were less likely to be admitted to hospital (OR 0.44; 95% CI 0.31 to 0.62; 12 studies; 960 patients) and heterogeneity (I(2) = 27%) was modest. This represents a reduction from 32 to 17 hospital admissions per 100 patients treated with ICS in comparison with placebo. Subgroup analysis of hospital admissions based on concomitant systemic corticosteroid use revealed that both subgroups indicated benefit from ICS in reducing hospital admissions (ICS and systemic corticosteroid versus systemic corticosteroid: OR 0.54; 95% CI 0.36 to 0.81; 5 studies; N = 433; ICS versus placebo: OR 0.27; 95% CI 0.14 to 0.52; 7 studies; N = 527). However, there was moderate heterogeneity in the subgroup using ICS in addition to systemic steroids (I(2) = 52%). Patients receiving ICS demonstrated small, significant improvements in peak expiratory flow (PEF: MD 7%; 95% CI 3% to 11%) and forced expiratory volume in one second (FEV(1): MD 6%; 95% CI 2% to 10%) at three to four hours post treatment). Only a small number of studies reported these outcomes such that they could be included in the meta-analysis and most of the studies in this comparison did not administer systemic corticosteroids to either treatment group. There was no evidence of significant adverse effects from ICS treatment with regard to tremor or nausea and vomiting. In the secondary analysis of studies comparing ICS alone versus systemic corticosteroid alone, heterogeneity among the studies complicated pooling of data or drawing reliable conclusions.
AUTHORS' CONCLUSIONS: ICS therapy reduces hospital admissions in patients with acute asthma who are not treated with oral or intravenous corticosteroids. They may also reduce admissions when they are used in addition to systemic corticosteroids; however, the most recent evidence is conflicting. There is insufficient evidence that ICS therapy results in clinically important changes in pulmonary function or clinical scores when used in acute asthma in addition to systemic corticosteroids. Also, there is insufficient evidence that ICS therapy can be used in place of systemic corticosteroid therapy when treating acute asthma. Further research is needed to clarify the most appropriate drug dosage and delivery device, and to define which patients are most likely to benefit from ICS therapy. Use of similar measures and reporting methods of lung function, and a common, validated, clinical score would be helpful in future versions of this meta-analysis.
全身用皮质类固醇疗法是急性哮喘治疗的核心。在这种情况下,吸入性皮质类固醇(ICS)的使用可能也有益处。
确定ICS对急诊科(ED)治疗的急性哮喘患者的益处。
我们从Cochrane Airways Group专业对照试验注册库中识别对照临床试验。还检索了纳入研究的参考文献、已知综述和教科书。最近一次检索时间为2012年9月。
我们纳入随机对照试验(RCT)和半随机对照试验。如果患者因急性哮喘就诊于急诊科或类似科室,除标准治疗外还接受ICS或安慰剂治疗,则纳入研究。两位综述作者独立选择潜在相关文章,然后独立选择纳入文章。两位综述作者独立评估方法学质量。本综述纳入了三种不同类型的研究:1)比较ICS与安慰剂,两组均未给予全身用皮质类固醇的研究;2)比较ICS与安慰剂,两组均给予全身用皮质类固醇的研究;3)比较单独使用ICS与全身用皮质类固醇的研究。分析时,前两种类型的研究作为单独亚组纳入主要分析(ICS与安慰剂),而第三种类型的研究纳入次要分析(ICS与全身用皮质类固醇)。
如果作者无法核实提取信息的有效性,则由两位综述作者独立提取数据。缺失数据从作者处获取或根据论文中呈现的其他数据计算得出。在适当情况下,个体和汇总的二分法结局报告为比值比(OR)及95%置信区间(CI)。在适当情况下,个体和汇总的连续性结局报告为均数差(MD)或标准化均数差(SMD)及95%CI。主要分析采用固定效应模型,敏感性分析采用随机效应模型。使用I²(I(2))统计量报告异质性。
20项试验被选入主要分析(13项儿科试验,7项成人试验),共1403例患者。接受ICS治疗的患者住院可能性较小(OR 0.44;95%CI 0.31至0.62;12项研究;960例患者),异质性(I(2)=27%)适中。与安慰剂相比,这意味着每100例接受ICS治疗的患者中,住院人数从32例降至17例。基于同时使用全身用皮质类固醇的住院亚组分析显示,两个亚组均表明ICS在减少住院方面有益(ICS与全身用皮质类固醇联合使用与全身用皮质类固醇:OR 0.54;95%CI 0.36至0.81;5项研究;N = 433;ICS与安慰剂:OR 0.27;95%CI 0.14至0.52;7项研究;N = 527)。然而,在除全身用皮质类固醇外还使用ICS的亚组中存在中度异质性(I(2)=52%)。接受ICS治疗的患者在治疗后3至4小时,呼气峰值流速(PEF:MD 7%;95%CI 3%至11%)和一秒用力呼气容积(FEV(1):MD 6%;95%CI 2%至10%)有小幅度但显著的改善。只有少数研究报告了这些结局,因此可纳入荟萃分析,且该比较中的大多数研究未对任何一组给予全身用皮质类固醇。没有证据表明ICS治疗在震颤或恶心呕吐方面有显著不良反应。在比较单独使用ICS与单独使用全身用皮质类固醇的研究的次要分析中,研究间的异质性使数据合并或得出可靠结论变得复杂。
ICS疗法可减少未接受口服或静脉用皮质类固醇治疗的急性哮喘患者的住院人数。当与全身用皮质类固醇联合使用时,它们也可能减少住院人数;然而,最新证据存在矛盾。没有足够证据表明在急性哮喘中除全身用皮质类固醇外使用ICS疗法会导致肺功能或临床评分出现具有临床意义的变化。此外,没有足够证据表明在治疗急性哮喘时ICS疗法可替代全身用皮质类固醇疗法。需要进一步研究以明确最合适的药物剂量和给药装置,并确定哪些患者最可能从ICS疗法中获益。在本荟萃分析的未来版本中,采用类似的肺功能测量和报告方法以及一种通用、经过验证的临床评分将有所帮助。