Kate Johnson

September 08, 2016

LONDON, United Kingdom — The addition of vitamin D supplements to standard asthma medication can lead to fewer severe asthma attacks in patients with mild to moderate asthma, according to a new Cochrane review.

But "caution is warranted in applying this evidence to clinical practice," write investigators, led by Adrian Martineau, PhD, from the Asthma UK Centre for Applied Research at Queen Mary University of London.

The results come from "relatively few trials, none of which has individually reported a statistically significant effect of vitamin D on risk of exacerbation requiring treatment with systemic corticosteroids as a prespecified outcome," they caution.

The review findings were presented here at the European Respiratory Society International Congress 2016.

"Only three trials reported any participant who experienced a severe exacerbation. The other trials either didn't look at that outcome or none of the patients in either arm experienced that outcome," Dr Martineau told Medscape Medical News.

The review assessed nine double-blind, placebo-controlled trials that involved 435 children and 658 adults with predominantly mild to moderate asthma.

Oral Vitamin D₃ Supplements

Oral vitamin D₃ (cholecalciferol) supplementation was given for 4 to 12 months, and dosing varied from 500 to 1200 IU/day, to weekly, monthly, or twice-monthly dosing, sometimes with boluses.

Overall, supplementation was associated with a significant reduction in the rate of asthma exacerbations treated with systemic corticosteroids (rate ratio, 0.63), meaning the average number of annual attacks decreased from 0.44 to 0.22 per person. However, this finding was based primarily on data from adults and should not be generalized to pediatric populations, Dr Martineau pointed out.

Supplementation also decreased the risk for exacerbations requiring hospitalization or a visit to the emergency department from six to around three per 100 patients (odds ratio, 0.39).

But vitamin D had little or no effect on lung function or on the day-to-day symptoms of asthma, and did not increase the risk for serious adverse events.

"What we don't know is whether the benefits of vitamin D were restricted just to patients who were vitamin D–deficient or whether they were experienced by everybody, irrespective of their baseline status," Dr Martineau explained.

Subgroup analyses are being conducted to answer that question.

For adults who have persistent exacerbations, measuring vitamin D levels would also be justified.

According to the review, it is estimated that about 1 billion people around the world have vitamin D levels below 75 nmol/L, which is generally considered insufficient; levels below 50 nmol/L are considered deficient.

In a large proportion of study participants, levels of vitamin D were deficient or insufficient. Mean/median baseline serum 25-hydroxyvitamin D concentrations ranged from 48 to 89 nmol/L. In a small minority of participants, levels were below 25 nmol/L, which is considered to be profoundly deficient.

"In the context of other vitamin D studies done by us and others, the benefits of supplementation tend to be stronger in those with lower levels," said Dr Martineau. "Our hypothesis is that we will see more marked effects in people with lower levels."

Vitamin D has an anti-inflammatory effect on the lungs and induces innate antimicrobial mechanisms, he explained.

"The data are very good for adults, but there is no evidence in this Cochrane review that vitamin D has this effect on children," said Fernando Martinez, MD, director of the Arizona Respiratory Center at the University of Arizona in Tucson.

"I suspect that it does, but it should be looked at separately so that we're basing our recommendations on data," he told Medscape Medical News.

"I think the association is there. At this point, it would be perfectly legitimate for general practitioners, pediatricians, and even pulmonologists who are following people with asthma to put them all on 500 to 1000 units of vitamin D a day," he added.

"For adults who have persistent exacerbations, measuring vitamin D levels would also be justified, and if they have low levels, you could give them even more," said Dr Martinez.

"In children, since to measure it you have to poke the child, I would suggest that we wait for more data. I'm quite convinced it's going to be that way, but I'm not willing to suggest a specific test for children without having data. Still, supplementation without testing is fine."

Dr Martineau and Dr Martinez have disclosed no relevant financial relationships.

European Respiratory Society (ERS) International Congress 2016: Abstract PA4112. Presented September 6, 2016.


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