ESPE Yearbook of Paediatric Endocrinology

JAMA. 2020 Aug 25;324(8):752–760. doi: 10.1001/jama.2020.12384. Abstract: https://pubmed.ncbi.nlm.nih.gov/32840597/

In brief: Several observational studies have linked low serum 25(OH)D levels to severe asthma exacerbations, lower lung function, and reduced response to corticosteroids. In this randomized controlled trial in children with persistent asthma and low vitamin D levels, vitamin D3 supplementation compared with placebo did not improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in these children.

Comment: Vitamin D has immune-modulatory and anti-inflammatory effects. Vitamin D may also attenuate viral-induced asthma attacks by reducing rhinovirus replication in bronchial epithelium. A meta-analysis of clinical trials including participant-level data showed that vitamin D3 supplementation was associated with lower risk of asthma exacerbations, but the pooled estimate was not significant among children < 16 years old. However, previous paediatric randomized trials have not focused on children with low vitamin D levels or who are at high risk for severe asthma exacerbations. Moreover, previous trials did not monitor vitamin D levels and did not show consistently higher levels after supplementation.

In this randomized trial, participants were randomized to vitamin D3, 4000 IU/d (n=96), or placebo (n=96) for 48 weeks, and maintained with fluticasone propionate, 176 μg/d (6–11 years old), or 220 μg/d (12–16 years old). Among 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D3 supplementation did not improve the primary outcome, time to a severe exacerbation: mean 240 days on vitamin D3 vs 253 days on placebo (mean difference, −13.1 days [95% CI, −42.6–16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69–1.85]; P=0.63). Likewise Vitamin D3 supplementation did not improve secondary outcomes: time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial.

This study has limitations as it was underpowered to, (a) assess if small difference in severe asthma exacerbation (37.5% in the vitamin D3 group and 34.4% in the placebo group) was statistically significant and, (b) to determine whether vitamin D3 supplementation reduces severe asthma exacerbations in children with vitamin D levels <20 ng/mL because only few participants had such levels. In addition, findings cannot be extrapolated to other age groups, including preschool children, or to settings with limited ability to monitor vitamin D levels.

To conclude, among children with persistent asthma and low vitamin D levels, this trial showed that vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in such patients.