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BACKGROUND

Oral corticosteroids are commonly used for acute preschool wheeze, although there is conflicting evidence of their benefit. We assessed the clinical efficacy of oral corticosteroids by means of a systematic review and individual participant data (IPD) meta-analysis.

METHODS

In this systematic review with IPD meta-analysis, we systematically searched eight databases (PubMed, Ovid Embase, CINAHLplus, CENTRAL, ClinicalTrials.gov, EudraCT, EU Clinical Trials Register, WHO Clinical Trials Registry) for randomised clinical trials published from Jan 1, 1994, to June 30, 2020, comparing oral corticosteroids with placebo in children aged 12 to 71 months with acute preschool wheeze in any setting based on the Population, Intervention, Comparison, Outcomes framework. We contacted principal investigators of eligible studies to obtain deidentified individual patient data. The primary outcome was change in wheezing severity score (WSS). A key secondary outcome length of hospital stay. We also calculated a pooled estimate of six commonly reported adverse events in the follow-up period of IPD datasets. One-stage and two-stage meta-analyses employing a random-effects model were used. This study is registered with PROSPERO, CRD42020193958.

FINDINGS

We identified 16 102 studies published between Jan 1, 1994, and June 30, 2020, from which there were 12 eligible trials after deduplication and screening. We obtained individual data from seven trials comprising 2172 children, with 1728 children in the eligible IPD age range; 853 (49·4%) received oral corticosteroids (544 [63·8%] male and 309 [36·2%] female) and 875 (50·6%) received placebo (583 [66·6%] male and 292 [33·4%] female). Compared with placebo, a greater change in WSS at 4 h was seen in the oral corticosteroids group (mean difference -0·31 [95% CI -0·38 to -0·24]; p=0·011) but not 12 h (-0·02 [-0·17 to 0·14]; p=0·68), with low heterogeneity between studies (I=0%; τ<0·001). Length of hospital stay was significantly reduced in the oral corticosteroids group (-3·18 h [-4·43 to -1·93]; p=0·0021; I=0%; τ<0·001). Subgroup analyses showed that this reduction was greatest in those with a history of wheezing or asthma (-4·54 h [-5·57 to -3·52]; p=0·0007). Adverse events were infrequently reported (four of seven datasets), but oral corticosteroids were associated with an increased risk of vomiting (odds ratio 2·27 [95% CI 0·87 to 5·88]; τ<0·001). Most datasets (six of seven) had a low risk of bias.

INTERPRETATION

Oral corticosteroids reduce WSS at 4 h and length of hospital stay in children with acute preschool wheeze. In those with a history of previous wheeze or asthma, oral corticosteroids provide a potentially clinically relevant effect on length of hospital stay.

FUNDING

Asthma UK Centre for Applied Research.

背景

口服皮质类固醇常用于治疗急性学龄前喘息，但它们的疗效存在相互矛盾的证据。我们通过系统评价和个体参与者数据（IPD）荟萃分析评估了口服皮质类固醇的临床疗效。

方法

在这项系统评价和 IPD 荟萃分析中，我们系统地检索了 8 个数据库（PubMed、Ovid Embase、CINAHLplus、CENTRAL、ClinicalTrials.gov、EudraCT、EU 临床试验注册处、世界卫生组织临床试验注册处），从 1994 年 1 月 1 日至 2020 年 6 月 30 日，比较了在任何环境下，12 至 71 个月大的急性学龄前喘息的儿童中，口服皮质类固醇与安慰剂的随机临床试验。我们联系了合格研究的主要研究者，以获得去识别的个体患者数据。主要结局是喘息严重程度评分（WSS）的变化。一个关键的次要结局是住院时间的长短。我们还计算了 IPD 数据集随访期间六个常见不良事件的汇总估计值。采用随机效应模型进行了单阶段和两阶段荟萃分析。这项研究在 PROSPERO 注册，CRD42020193958。

发现

我们从 1994 年 1 月 1 日至 2020 年 6 月 30 日发表的 16102 项研究中进行了筛选，其中有 12 项合格的试验。我们从 7 项试验中获得了个体数据，这些试验共涉及 2172 名儿童，其中 7 项试验中 1728 名儿童的年龄在合格的 IPD 范围内；853 名（49.4%）接受了口服皮质类固醇（544 名[63.8%]为男性，309 名[36.2%]为女性），875 名（50.6%）接受了安慰剂（583 名[66.6%]为男性，292 名[33.4%]为女性）。与安慰剂相比，口服皮质类固醇组在 4 小时时 WSS 的变化更大（平均差异-0.31 [95% CI -0.38 至 -0.24]；p=0.011），但 12 小时时没有差异（-0.02 [-0.17 至 0.14]；p=0.68），研究之间的异质性较低（I=0%；τ<0.001）。口服皮质类固醇组的住院时间明显缩短（-3.18 小时[-4.43 至-1.93]；p=0.0021；I=0%；τ<0.001）。亚组分析表明，在有喘息或哮喘病史的患者中，这种减少幅度最大（-4.54 小时[-5.57 至-3.52]；p=0.0007）。不良事件很少报告（七个数据集中有四个），但口服皮质类固醇与呕吐风险增加相关（比值比 2.27 [95% CI 0.87 至 5.88]；τ<0.001）。大多数数据集（七个数据集中有六个）的偏倚风险较低。

解释

口服皮质类固醇可降低急性学龄前喘息儿童的 WSS 和住院时间。在有喘息或哮喘病史的患者中，口服皮质类固醇可能对住院时间有潜在的临床相关影响。

资助

英国哮喘协会应用研究中心。

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