Vitamin D Supplementation for Childhood Asthma: A Systematic Review and Meta-Analysis

IMPORTANCE: There is growing evidence that vitamin D plays a role in the pathogenesis of asthma but it is unclear whether supplementation during childhood may improve asthma outcomes. OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of vitamin D supplementation as a treatment or adjunct treatment for asthma. DATA SOURCES: We searched MEDLINE, Embase, CENTRAL, and CINAHL through July 2014. STUDY SELECTION: We included RCTs that evaluated vitamin D supplementation in children versus active control or placebo for asthma. DATA EXTRACTION AND SYNTHESIS: One reviewer extracted data and one reviewer verified data accuracy. We qualitatively summarized the main results of efficacy and safety and meta-analyzed data on comparable outcomes across studies. We used GRADE for strength of evidence. MAIN OUTCOME MEASURES: Main planned outcomes measures were ED visits and hospitalizations. As secondary outcomes, we examined measures of asthma control, including frequency of asthma exacerbations, asthma symptom scores, measures of lung function, β(2)-agonist use and daily steroid use, adverse events and 25-hydroxyvitamin D levels. RESULTS: Eight RCTs (one parallel, one crossover design) comprising 573 children aged 3 to 18 years were included. One study (moderate-quality, n = 100) reported significantly less ED visits for children treated with vitamin D. No other studies examined the primary outcome (ED visits and hospitalizations). There was a reduced risk of asthma exacerbations in children receiving vitamin D (low-quality; RR 0.41, 95% CI 0.27 to 0.63, 3 studies, n = 378). There was no significant effect for asthma symptom scores and lung function. The serum 25(OH)D level was higher in the vitamin D group at the end of the intervention (low-quality; MD 19.66 nmol/L, 95% CI 5.96 nmol/L to 33.37 nmol/L, 5 studies, n = 167). LIMITATIONS: We identified a high degree of clinical diversity (interventions and outcomes) and methodological heterogeneity (sample size and risk of bias) in included trials. CONCLUSIONS AND RELEVANCE: Randomized controlled trials provide some low-quality evidence to support vitamin D supplementation for the reduction of asthma exacerbations. Evidence on the benefits of vitamin D supplementation for other asthma-related outcomes in children is either limited or inconclusive. We recommend that future trials focus on patient-relevant outcomes that are comparable across studies, including standardized definitions of asthma exacerbations.