PHILADELPHIA — Children with asthma and on treatment with inhaled corticosteroids who had insufficient blood levels of vitamin D had an increased risk of asthma exacerbations during 4 years of follow-up in a study with 305 children.
The results are only suggestive, because the study wasn't designed to assess the impact of vitamin D levels on asthma, but they warrant further study into a possible role that vitamin D might play in modifying the effect of inhaled corticosteroid in children with asthma.
The results suggest that boosting blood vitamin D levels might improve responsiveness to inhaled corticosteroids in asthmatic children, Dr. Augusto A. Litonjua said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The study included 305 children with asthma enrolled in the inhaled-budesonide group of the Childhood Asthma Management Program. It was designed to assess the safety and efficacy of inhaled budesonide (Pulmicort), compared with nedocromil (Tilade) or placebo.
The primary outcome was the incidence of severe asthma exacerbations, defined as emergency department visits or hospitalization for asthma exacerbations. In this post hoc analysis, Dr. Litonjua, a pulmonologist at the Channing Laboratory of Brigham and Women's Hospital in Boston, and his associates measured blood levels of serum 25-hydroxyvitamin D (25[OH]D), the primary, circulating biomarker of vitamin D status, in blood specimens collected from patients 2 weeks before their randomization in the trial. The post hoc analysis did not receive any commercial funding.
Patients in the inhaled budesonide group were dichotomized by their blood 25(OH)D level. Those with a level of 30 ng/mL or less were categorized as having an insufficient level; those with greater than 30 ng/mL were considered to have sufficient vitamin D.
Sufficient levels existed in 70% of the 305 patients, and insufficient levels were in 30%; the overall average level of 25(OH)D was about 40 ng/dL. The average age of all children in the inhaled-budesonide subgroup was 9 years. About 59% of the children were boys, and 65% were white.
During follow-up, severe asthma exacerbations occurred in 24% of the children with insufficient vitamin D and in 18% of the children with sufficient vitamin D. In several analytic models that adjusted for potential confounding differences at baseline, the increased rate of exacerbations was significantly linked with vitamin D insufficiency. Adjusters included age, height, gender, pulmonary function, race, ethnicity, seasonality, and history of exacerbations in the year prior to the study.
In these adjusted models, children with insufficient vitamin D were about 70% more likely than those with sufficient vitamin D to have exacerbations. However, in a model that included all of these adjustments plus study center, the increased risk for exacerbations was no longer statistically significant, although it was 60% higher in the insufficient vitamin D group.
There are several plausible, physiologic links between vitamin D and asthma severity. Vitamin D acts on bronchial smooth muscle cells and may play a role in the airway remodeling that occurs in long-standing asthma, and the vitamin's receptors and metabolic enzymes exist both in immune cells and lung cells.