Low Vitamin D May Blunt Effectiveness of Asthma Treatment

July 13, 2012 — When using inhaled corticosteroids to treat patients with persistent asthma, vitamin D levels should be closely monitored and supplemented, if necessary, according to results from a multicenter placebo-controlled study of 1041 children with mild to moderate persistent asthma. Ann Chen, MD, MPH, assistant professor in the Department of Population Medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, and colleagues found that children with asthma who are deficient in vitamin D show less improvement over the course of a year’s therapy with corticosteroids than do children who have more normal levels.

“In asthmatic children treated with inhaled corticosteroids, vitamin D deficiency is associated with poorer lung function than [in] children with vitamin D insufficiency or sufficiency,” the authors write.

The findings were published online July 13 in the American Journal of Respiratory and Critical Care Medicine.

Dr. Chen and colleagues note that the prevalence of both asthma and vitamin D deficiency have increased in recent years, suggesting there may be a causal link between the 2. “Multiple studies have supported the hypothesis that asthma and vitamin D deficiency are related,” they write, “but few studies have examined the direct effects of vitamin D levels and corticosteroid treatment on lung function in children with asthma.”

To look more closely into that possible association, the investigators analyzed data from the Childhood Asthma Management Program, a multicenter trial of 1041 children diagnosed with mild to moderate persistent asthma. All the children were between 5 and 12 years of age.

On the children’s entry into the study, administrators measured levels of 25-hydroxyvitamin D in their serum and then randomly assigned them to receive 1 of 3 agents: the inhaled corticosteroid budesonide, the nonsteroidal anti-inflammatory agent nedocromil, or placebo. Data regarding baseline vitamin D levels were available for 1024 children.

Spirometry readings were obtained before and after the children used their inhalers. Those tests were conducted at intake into the study and again after a year of therapy.

The investigators also categorized the children into 3 groups according to their serum levels of vitamin D: those who had sufficient levels (>30 ng/mL), those deemed to have insufficient levels (20 – 30 ng/mL), and those with deficient levels (<20 ng/mL).

Main outcome measures were changes in prebronchodilator forced expiratory volume in 1 second (FEV₁), bronchodilator response, and provocative concentration of methacholine producing a 20% decline in FEV₁.

The researchers report that of the 1024 children, 663 (nearly 65%) had sufficient levels of vitamin D, 260 (just over 25%) had insufficient levels, and 101 (roughly 10%) had deficient levels.

Compared with children who had sufficient or insufficient levels of vitamin D, those with deficient levels were more likely to be older and black and to have a higher body mass index, the researchers write.

Among children being treated with corticosteroids, those who were vitamin D deficient were less likely than other children taking the same drug to show big improvements in prebronchodilator FEV₁ scores after 12 months of treatment.

More specifically, children with insufficient levels of vitamin D showed a 330-mL increase, those with sufficient levels showed a 290-mL increase, and children with vitamin D deficiencies had only a 140-mL increase in prebronchodilator FEV₁. That difference was significant to a P value of < .007, after adjustments for age, sex, race, body mass index, number of visits to emergency departments, and the season of the year that serum for the vitamin D specimen had been drawn.

The investigators do acknowledge a couple of limitations of the study; namely, that the sample size of children with vitamin D deficiencies was relatively small (101 children) and that vitamin D levels were assessed only once, on entry into the trial.

Even so, Dr. Wu and colleagues say the present study is the first to suggest that vitamin D sufficiency in patients treated with inhaled corticosteroids is associated with improved lung function in patients with mild to moderate persistent asthma. They suggest monitoring vitamin D levels and, if they are found to be low, considering supplementation.

This study was funded by the National Heart, Lung, and Blood Institute, the Childhood Asthma Management Program, and the National Center for Research Resources. The authors have disclosed no relevant financial relationships.

Am J Respir Crit Care Med. Published online July 13, 2012.