Vitamin D supplementation fails to improve time to severe asthma exacerbation in children
Vitamin D supplementation, compared with placebo, did not improve time to severe asthma exacerbation in children with persistent asthma and low vitamin D levels, according to new data published in JAMA.
“While observational studies have reported associations between low vitamin D levels and childhood asthma outcomes, randomized clinical trials have provided less encouraging evidence of a protective effect of vitamin D3 supplementation against morbidity from asthma,” Erick Forno, MD, MPH, assistant professor of pediatrics at the University of Pittsburgh School of Medicine and the UPMC Children’s Hospital of Pittsburgh, and colleagues wrote.
Researchers conducted the randomized, double-blind, placebo-controlled VDKA trial to assess the benefit of vitamin D supplementation compared with placebo. Researchers enrolled children with asthma (aged 6 to 16 years) who were taking low-dose inhaled corticosteroids and had serum 25-hydroxyvitamin D levels less than 30 ng/mL. Enrollment began in 2016 and the trial was terminated early due to futility in March 2019; follow-up ended in September 2019.
Participants were randomly assigned to vitamin D3 4,000 IU per day (n = 96) or placebo (n = 96) for 48 weeks, and maintained with fluticasone propionate (176 µg per day for patients aged 6 to 11 years and 220 µg per day for patients aged 12 to 16 years).
Primary outcome was time to severe asthma exacerbation. Secondary outcomes included time to viral-induced severe exacerbation, proportion of patients where the dose of inhaled corticosteroid was reduced and cumulative fluticasone dose.
In total, 192 participants were randomly assigned to vitamin D supplementation or placebo (mean age, 9.8 years; 40% girls); 180 (93.8%) completed the trial.
More than one-third (37.5%) of patients in the vitamin D group and placebo group (34.4%) experienced one or more severe exacerbations during the trial. Vitamin D supplementation did not significantly improve time to severe exacerbation compared with placebo, with a mean time to exacerbation of 240 days in the vitamin D group vs. 253 days in the placebo group (adjusted HR = 1.13; 95% CI, 0.69-1.85).
Compared with placebo, vitamin D supplementation did not significantly improve any of the secondary outcomes.
Serious adverse events were similar in both groups, with 11 events in the vitamin D group vs. nine in the placebo group.
“The reason [these trial results are] important is there are colleagues around this country and worldwide who are testing vitamin D levels for kids with asthma and giving them vitamin D,” Juan C. Celedón, MD, DrPH, chief of pediatric pulmonary medicine at UPMC Children’s Hospital of Pittsburgh, said in a press release. “As a system, it costs a lot of money to run all these tests and give the supplements.”
The VDKA trial results differ from previous studies conducted in Costa Rica, the U.S., Canada and Puerto Rico, results of which showed children with naturally low vitamin D levels had worse asthma effects. Celedón noted in the press release that one cannot draw conclusions about whether very low vitamin D levels contribute to asthma exacerbations, but he said those children would receive vitamin D supplementation either way because of known effects on bone health.
“The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in this group of patients,” the researchers concluded.