Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data.
Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data.
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DOI：
10.1016/s2213-2600(17)30306-5
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Martineau AR
中科院分区：
文献类型：
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作者：
Jolliffe DA;Greenberg L;Hooper RL;Griffiths CJ;Camargo CA Jr;Kerley CP;Jensen ME;Mauger D;Stelmach I;Urashima M;Martineau AR
先前对随机对照试验的汇总数据荟萃分析表明，维生素D补充剂可降低需要全身皮质类固醇治疗的哮喘急性发作的发生率。这种影响是否仅限于低基线维生素D状态的患者尚不清楚。对于这项系统性综述以及对个体受试者数据的一步和两步荟萃分析，我们检索了MEDLINE、Embase、科克伦对照试验中心和Web of Science，以获得在数据库建立至2016年10月26日期间发表的报告哮喘急性发作发生率的关于哮喘患者补充维生素D3或维生素D2的双盲、安慰剂对照、随机对照试验。我们分析了每个合格试验的主要研究者要求的个体受试者数据，调整了年龄和性别，并按研究进行聚类。主要结局是需要全身皮质类固醇治疗的哮喘急性发作的发生率。使用混合效应回归模型获得合并干预效应和95%CI。进行亚组分析，以确定维生素D对哮喘急性发作风险的影响是否因基线25-羟基维生素D（25[OH]D）浓度、年龄、种族或人种、体重指数、维生素D给药方案、吸入性皮质类固醇的使用或研究结束时的25（OH）D水平而异;根据性别和研究持续时间进行事后亚组分析。本研究在PROSPERO注册，编号CRD 42014013953。我们的检索确定了483项独特的研究，其中8项是合格的随机对照试验（共1078例受试者）。我们为每项研究寻找个体参与者数据，并获得了7项研究（955名参与者）的数据。补充维生素D可降低所有受试者中需要全身皮质类固醇治疗的哮喘急性发作率（校正后的发病率比[aIRR] 0·74，95% CI 0·56-0·97; p=0·03; 7项研究中955例受试者;高质量证据）。维生素D组和安慰剂组在至少有一次急性发作或首次急性发作时间的受试者比例方面没有显著差异。对全身性皮质类固醇治疗的哮喘急性发作率进行亚组分析，结果显示，基线25（OH）D低于25 nmol/L的受试者具有保护作用（aIRR 0.33，0.11 - 0.98; p= 0.046; 3项研究中92名参与者;中等质量证据），但基线25（OH）D水平较高的参与者则不然（aIRR 0·77，0·58-1·03; p=0·08;六项研究中有764名参与者;中等质量证据; p相互作用=0·25）。所有其他亚组分析的相互作用的p值也高于0.05;因此，我们没有表明这种干预措施在任何一个亚组中的效果比在另一个亚组中更强。6项研究被评估为偏倚风险较低，1项研究被评估为偏倚风险不明确。两步荟萃分析未发现效应异质性的证据（I2=0·0，p=0·56）。补充维生素D可降低需要全身皮质类固醇治疗的哮喘急性发作的发生率。我们没有发现明确的证据表明这种干预的效果在不同的患者亚组之间存在差异。国家卫生研究所卫生技术评估方案（参考编号：13/03/25）。
A previous aggregate data meta-analysis of randomised controlled trials showed that vitamin D supplementation reduces the rate of asthma exacerbations requiring treatment with systemic corticosteroids. Whether this effect is restricted to patients with low baseline vitamin D status is unknown. For this systematic review and one-step and two-step meta-analysis of individual participant data, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for double-blind, placebo-controlled, randomised controlled trials of vitamin D3 or vitamin D2 supplementation in people with asthma that reported incidence of asthma exacerbation, published between database inception and Oct 26, 2016. We analysed individual participant data requested from the principal investigator for each eligible trial, adjusting for age and sex, and clustering by study. The primary outcome was the incidence of asthma exacerbation requiring treatment with systemic corticosteroids. Mixed-effects regression models were used to obtain the pooled intervention effect with a 95% CI. Subgroup analyses were done to determine whether effects of vitamin D on risk of asthma exacerbation varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, age, ethnic or racial origin, body-mass index, vitamin D dosing regimen, use of inhaled corticosteroids, or end-study 25(OH)D levels; post-hoc subgroup analyses were done according to sex and study duration. This study was registered with PROSPERO, number CRD42014013953. Our search identified 483 unique studies, eight of which were eligible randomised controlled trials (total 1078 participants). We sought individual participant data for each and obtained it for seven studies (955 participants). Vitamin D supplementation reduced the rate of asthma exacerbation requiring treatment with systemic corticosteroids among all participants (adjusted incidence rate ratio [aIRR] 0·74, 95% CI 0·56–0·97; p=0·03; 955 participants in seven studies; high-quality evidence). There were no significant differences between vitamin D and placebo in the proportion of participants with at least one exacerbation or time to first exacerbation. Subgroup analyses of the rate of asthma exacerbations treated with systemic corticosteroids revealed that protective effects were seen in participants with baseline 25(OH)D of less than 25 nmol/L (aIRR 0·33, 0·11–0·98; p=0·046; 92 participants in three studies; moderate-quality evidence) but not in participants with higher baseline 25(OH)D levels (aIRR 0·77, 0·58–1·03; p=0·08; 764 participants in six studies; moderate-quality evidence; pinteraction=0·25). p values for interaction for all other subgroup analyses were also higher than 0·05; therefore, we did not show that the effects of this intervention are stronger in any one subgroup than in another. Six studies were assessed as being at low risk of bias, and one was assessed as being at unclear risk of bias. The two-step meta-analysis did not reveal evidence of heterogeneity of effect (I2=0·0, p=0·56). Vitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall. We did not find definitive evidence that effects of this intervention differed across subgroups of patients. Health Technology Assessment Program, National Institute for Health Research (reference number 13/03/25).