Kirkland Scott W, Vandenberghe Christine, Voaklander Britt, Nikel Taylor, Campbell Sandra, Rowe Brian H
Department of Emergency Medicine, University of Alberta, Edmonton, AB, Canada.
John W. Scott Health Sciences Library, University of Alberta, Edmonton, AB, Canada.
Cochrane Database Syst Rev. 2017 Jan 11;1(1):CD001284. doi: 10.1002/14651858.CD001284.pub2.
Inhaled short-acting anticholinergics (SAAC) and short-acting beta₂-agonists (SABA) are effective therapies for adult patients with acute asthma who present to the emergency department (ED). It is unclear, however, whether the combination of SAAC and SABA treatment is more effective in reducing hospitalisations compared to treatment with SABA alone.
To conduct an up-to-date systematic search and meta-analysis on the effectiveness of combined inhaled therapy (SAAC + SABA agents) vs. SABA alone to reduce hospitalisations in adult patients presenting to the ED with an exacerbation of asthma.
We searched MEDLINE, Embase, CINAHL, SCOPUS, LILACS, ProQuest Dissertations & Theses Global and evidence-based medicine (EBM) databases using controlled vocabulary, natural language terms, and a variety of specific and general terms for inhaled SAAC and SABA drugs. The search spanned from 1946 to July 2015. The Cochrane Airways Group provided search results from the Cochrane Airways Group Register of Trials which was most recently conducted in July 2016. An extensive search of the grey literature was completed to identify any other potentially relevant studies.
Included studies were randomised or controlled clinical trials comparing the effectiveness of combined inhaled therapy (SAAC and SABA) to SABA treatment alone to prevent hospitalisations in adults with acute asthma in the emergency department. Two independent review authors assessed studies for inclusion using pre-determined criteria.
For dichotomous outcomes, we calculated individual and pooled statistics as risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) using a random-effects model and reporting heterogeneity (I²). For continuous outcomes, we reported individual trial results using mean differences (MD) and pooled results as weighted mean differences (WMD) or standardised mean differences (SMD) with 95% CIs using a random-effects model.
We included 23 studies that involved a total of 2724 enrolled participants. Most studies were rated at unclear or high risk of bias.Overall, participants receiving combination inhaled therapy were less likely to be hospitalised (RR 0.72, 95% CI 0.59 to 0.87; participants = 2120; studies = 16; I² = 12%; moderate quality of evidence). An estimated 65 fewer patients per 1000 would require hospitalisation after receiving combination therapy (95% 30 to 95), compared to 231 per 1000 patients receiving SABA alone. Although combination inhaled therapy was more effective than SABA treatment alone in reducing hospitalisation in participants with severe asthma exacerbations, this was not found for participants with mild or moderate exacerbations (test for difference between subgroups P = 0.02).Participants receiving combination therapy were more likely to experience improved forced expiratory volume in one second (FEV₁) (MD 0.25 L, 95% CI 0.02 to 0.48; participants = 687; studies = 6; I² = 70%; low quality of evidence), peak expiratory flow (PEF) (MD 36.58 L/min, 95% CI 23.07 to 50.09; participants = 1056; studies = 12; I² = 25%; very low quality of evidence), increased percent change in PEF from baseline (MD 24.88, 95% CI 14.83 to 34.93; participants = 551; studies = 7; I² = 23%; moderate quality of evidence), and were less likely to return to the ED for additional care (RR 0.80, 95% CI 0.66 to 0.98; participants = 1180; studies = 5; I² = 0%; moderate quality of evidence) than participants receiving SABA alone.Participants receiving combination inhaled therapy were more likely to experience adverse events than those treated with SABA agents alone (OR 2.03, 95% CI 1.28 to 3.20; participants = 1392; studies = 11; I² = 14%; moderate quality of evidence). Among patients receiving combination therapy, 103 per 1000 were likely to report adverse events (95% 31 to 195 more) compared to 131 per 1000 patients receiving SABA alone.
AUTHORS' CONCLUSIONS: Overall, combination inhaled therapy with SAAC and SABA reduced hospitalisation and improved pulmonary function in adults presenting to the ED with acute asthma. In particular, combination inhaled therapy was more effective in preventing hospitalisation in adults with severe asthma exacerbations who are at increased risk of hospitalisation, compared to those with mild-moderate exacerbations, who were at a lower risk to be hospitalised. A single dose of combination therapy and multiple doses both showed reductions in the risk of hospitalisation among adults with acute asthma. However, adults receiving combination therapy were more likely to experience adverse events, such as tremor, agitation, and palpitations, compared to patients receiving SABA alone.
吸入性短效抗胆碱能药物（SAAC）和短效β₂受体激动剂（SABA）是成年急性哮喘患者到急诊科就诊时的有效治疗方法。然而，与单独使用SABA治疗相比，SAAC和SABA联合治疗在减少住院方面是否更有效尚不清楚。
对联合吸入疗法（SAAC+SABA药物）与单独使用SABA减少急诊科就诊的成年哮喘急性加重患者住院率的有效性进行最新的系统检索和荟萃分析。
我们使用控制词汇、自然语言术语以及吸入性SAAC和SABA药物的各种特定和通用术语，检索了MEDLINE、Embase、CINAHL、SCOPUS、LILACS、ProQuest Dissertations & Theses Global和循证医学（EBM）数据库。检索时间跨度为1946年至2015年7月。Cochrane气道组提供了2016年7月最近进行的Cochrane气道组试验注册库的检索结果。对灰色文献进行了广泛检索，以识别任何其他潜在相关研究。
纳入的研究为随机或对照临床试验，比较联合吸入疗法（SAAC和SABA）与单独使用SABA治疗预防急诊科成年急性哮喘患者住院的有效性。两名独立的综述作者使用预先确定的标准评估纳入研究。
对于二分法结局，我们使用随机效应模型计算个体和合并统计量，以风险比（RR）或比值比（OR）及95%置信区间（CI）表示，并报告异质性（I²）。对于连续性结局，我们使用随机效应模型，以均数差（MD）报告个体试验结果，以加权均数差（WMD）或标准化均数差（SMD）及95%CI报告合并结果。
我们纳入了23项研究，共2724名受试者。大多数研究的偏倚风险为不清楚或高风险。总体而言，接受联合吸入疗法的受试者住院可能性较小（RR 0.72，95%CI 0.59至0.87；受试者=2120；研究=16；I²=12%；证据质量中等）。与每1000名单独接受SABA治疗的患者中有231人住院相比，估计每1000名接受联合治疗的患者中住院人数少65人（95% 30至95）。虽然联合吸入疗法在减少重度哮喘急性加重受试者的住院方面比单独使用SABA治疗更有效，但在轻度或中度急性加重受试者中未发现此差异（亚组间差异检验P=0.02）。接受联合治疗的受试者一秒用力呼气量（FEV₁）改善的可能性更大（MD 0.25 L，95%CI 0.02至0.48；受试者=687；研究=6；I²=70%；证据质量低），呼气峰值流速（PEF）（MD 36.58 L/min，95%CI 23.07至50.09；受试者=1056；研究=12；I²=25%；证据质量极低），PEF自基线的增加百分比变化（MD 24.88，95%CI 14.83至34.93；受试者=551；研究=7；I²=23%；证据质量中等），且与单独接受SABA治疗的受试者相比，返回急诊科接受额外治疗的可能性更小（RR 0.80，95%CI 0.66至0.98；受试者=1180；研究=5；I²=0%；证据质量中等）。接受联合吸入疗法的受试者比单独接受SABA药物治疗的受试者更易发生不良事件（OR 2.03，95%CI 1.
