Abstract：
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.
RESULTS: 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 (I2=0%; τ2<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; I2=0%; τ2<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]; pinteraction=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]; τ2<0·001). Most datasets (six of seven) had a low risk of bias.
CONCLUSIONS: 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.
BACKGROUND: Asthma UK Centre for Applied Research.
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.
RESULTS: 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 (I2=0%; τ2<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; I2=0%; τ2<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]; pinteraction=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]; τ2<0·001). Most datasets (six of seven) had a low risk of bias.
CONCLUSIONS: 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.
BACKGROUND: Asthma UK Centre for Applied Research.
摘要：
背景：口服皮质类固醇通常用于急性学龄前喘息，尽管它们的益处有相互矛盾的证据。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：在这篇IPD荟萃分析的系统综述中，我们系统地搜索了八个数据库(PubMed，OvidEmbase,CINAHLplus,中部,ClinicalTrials.gov,EudraCT,欧盟临床试验注册，WHO临床试验注册），用于1994年1月1日至2020年6月30日发表的随机临床试验，比较了12至71个月儿童的口服皮质类固醇和安慰剂，并根据人口在任何情况下患有急性学龄前哮喘，干预,比较,成果框架。我们联系了符合条件的研究的主要研究者，以获得未识别的个体患者数据。主要结果是喘息严重程度评分（WSS）的变化。住院时间的关键次要结局。我们还计算了在IPD数据集的随访期内六个常见不良事件的汇总估计值。采用随机效应模型的一阶段和两阶段荟萃分析。这项研究在PROSPERO注册，CRD42020193958。
结果：我们确定了1994年1月1日至2020年6月30日之间发表的16102项研究，其中有12项经过重复数据删除和筛选的合格试验。我们从包含2172名儿童的7项试验中获得了个体数据，符合IPD年龄范围的1728名儿童;853名(49·4%)接受口服皮质类固醇(男性544例[63·8%],女性309例[36·2%]),875名(50·6%)接受安慰剂(男性583例[66·6%],女性292例[33·4%]).与安慰剂相比，口服糖皮质激素组4h时WSS的变化更大（平均差-0·31[95％CI-0·38至-0·24]；p=0·011），但12h时没有变化（-0·02[-0·17至0·14]；p=0·68），研究间异质性低(I2=0%；τ2<0·001)。口服糖皮质激素组的住院时间显着减少（-3·18h[-4·43至-1·93]；p=0·0021；I2=0％；τ2<0·001）。亚组分析表明，这种减少在有喘息或哮喘病史的患者中最大（-4·54h[-5·57至-3·52]；pinteraction=0·0007）。不良事件很少报告(七个数据集中的四个)，但口服糖皮质激素与呕吐风险增加相关(比值比2·27[95%CI0·87~5·88];τ2<0·001)。大多数数据集（七个中的六个）的偏倚风险较低。
结论：口服糖皮质激素可降低学龄前急性喘息患儿4小时的WSS和住院时间。在那些有喘息或哮喘病史的人中，口服糖皮质激素对住院时间有潜在的临床相关影响.
背景：哮喘英国应用研究中心。
方法：在这篇IPD荟萃分析的系统综述中，我们系统地搜索了八个数据库(PubMed，OvidEmbase,CINAHLplus,中部,ClinicalTrials.gov,EudraCT,欧盟临床试验注册，WHO临床试验注册），用于1994年1月1日至2020年6月30日发表的随机临床试验，比较了12至71个月儿童的口服皮质类固醇和安慰剂，并根据人口在任何情况下患有急性学龄前哮喘，干预,比较,成果框架。我们联系了符合条件的研究的主要研究者，以获得未识别的个体患者数据。主要结果是喘息严重程度评分（WSS）的变化。住院时间的关键次要结局。我们还计算了在IPD数据集的随访期内六个常见不良事件的汇总估计值。采用随机效应模型的一阶段和两阶段荟萃分析。这项研究在PROSPERO注册，CRD42020193958。
结果：我们确定了1994年1月1日至2020年6月30日之间发表的16102项研究，其中有12项经过重复数据删除和筛选的合格试验。我们从包含2172名儿童的7项试验中获得了个体数据，符合IPD年龄范围的1728名儿童;853名(49·4%)接受口服皮质类固醇(男性544例[63·8%],女性309例[36·2%]),875名(50·6%)接受安慰剂(男性583例[66·6%],女性292例[33·4%]).与安慰剂相比，口服糖皮质激素组4h时WSS的变化更大（平均差-0·31[95％CI-0·38至-0·24]；p=0·011），但12h时没有变化（-0·02[-0·17至0·14]；p=0·68），研究间异质性低(I2=0%；τ2<0·001)。口服糖皮质激素组的住院时间显着减少（-3·18h[-4·43至-1·93]；p=0·0021；I2=0％；τ2<0·001）。亚组分析表明，这种减少在有喘息或哮喘病史的患者中最大（-4·54h[-5·57至-3·52]；pinteraction=0·0007）。不良事件很少报告(七个数据集中的四个)，但口服糖皮质激素与呕吐风险增加相关(比值比2·27[95%CI0·87~5·88];τ2<0·001)。大多数数据集（七个中的六个）的偏倚风险较低。
结论：口服糖皮质激素可降低学龄前急性喘息患儿4小时的WSS和住院时间。在那些有喘息或哮喘病史的人中，口服糖皮质激素对住院时间有潜在的临床相关影响.
背景：哮喘英国应用研究中心。
