Findings from a new study in JAMA do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in children with persistent asthma.
Previous observational studies have linked vitamin D levels to severe asthma exacerbations, but findings from a new study do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in children with persistent asthma. The findings were published in JAMA.
While past observational studies have shown an association between vitamin D levels and childhood asthma outcomes, randomized controlled trials have not provided the same evidence.
"With observational studies, you never know—is vitamin D causing asthma to be worse or do kids with worse asthma end up having lower vitamin D?" study lead author Juan C. Celedón, MD, DrPH, chief of pediatric pulmonary medicine at UPMC Children's Hospital of Pittsburgh, said in a statement.
In the Vitamin D to Prevent Severe Asthma Exacerbations study, researchers recruited 192 participants from 7 sites across Boston, but only 180 completed the trial. Patients were randomly assigned to either daily placebo capsules or daily vitamin D3, 4000 IU, plus inhaled fluticasone propionate. Children between the ages of 6 and 11 years received 88 mcg of inhaled fluticasone propionate twice per day, while children aged 12 and older received 110 mcg twice per day. The participants were randomized to their groups after a 4-week run-in period in which they all received placebo capsules plus the inhaled fluticasone.
However, after a second interim analysis, there had been 26 events in the 90 participants (28.9%) in the placebo group and 25 events in the 91 participants (27.5%) in the vitamin D group. The data and safety monitoring board “recommended that no new participants be randomized due to futility.”
Nearly all (94.4%) of the patients in the vitamin D group achieved a level of 30 ng/mL or higher compared with just 40.7% in the placebo group at 16 weeks. By week 48, 87.2% in the vitamin D group achieved that level compared with 30.1% in the placebo group. At baseline, 23% of participants had vitamin D levels less than 20 ng/mL and 12 had levels that low at the exit visit.
The primary end point was time to a severe asthma exacerbation, defined as either the use of systemic corticosteroids for at least 3 days or a hospitalization or emergency department visit because of asthma, requiring systemic corticosteroids. During the trial, 37.5% of patients in the vitamin D group and 34.4% patients in the placebo group had at least 1 severe asthma exacerbation. The mean time to severe exacerbation was 240 days in the vitamin D group and 253 days in the placebo group.
The researchers also found that, compared with placebo, vitamin D3 supplementation did not significantly prolong the time to first viral-induced severe exacerbation. In addition, the proportion of patients whose inhaled corticosteroid dose could be halved was not significantly different between the groups by the midpoint of the trial.
The authors concluded that their study findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbation in children.
“Among children with persistent asthma and low vitamin D levels, vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation,” they wrote.
Forno E, Bacherier LB, Phipatanakul W, et al. Effect of Vitamin D3 supplementation on severe asthma exacerbations in children with asthma and low vitamin D levels. JAMA. 2020;324(8):752. doi:10.1001/jama.2020.12384