Assessment of the relationship between vitamin D deficiency and asthma outcomes in Peruvian children

Background: Prior evidence suggests that vitamin D deficiency may play a role in increased risk of asthma, markers of asthma control, and allergic disease. However, the results of these studies have been conflicted, and studies of children in low- and middle-income countries are lacking. In addition, recent evidence has found stronger associations of free 25-hydroxyvitamin D [25(OH)D] than total 25(OH)D for certain health outcomes. No studies to date have examined the relationship between free 25(OH)D and asthma, atopy, or pulmonary function. Methods: We conducted an unmatched case-control study of 543 children 9 to 19 years of age with asthma and 341 healthy controls living in Lima, Peru. We first examined the risk factors driving vitamin D deficiency in our population. We then examined the association of total 25(OH)D concentrations with asthma, markers of allergy and lung inflammation, and pulmonary function. Finally, we examined the association of free 25(OH)D concentrations with asthma outcomes in a subset of 288 children. Results: There was a high prevalence of vitamin D insufficiency in these communities. Season of blood draw and study community were the most important independent predictors of vitamin D deficiency. Vitamin D-rich food intake was also associated with 25(OH)D concentrations, and body mass index was associated in one of the two communities. Serum 25(OH)D concentrations were inversely associated with current asthma in one study community with a high prevalence of deficiency. Finally, atopy, FEV1 and FVC were more strongly linked to free 25(OH)D than to total 25(OH)D concentrations. Conclusions: Studies of vitamin D deficiency and disease should consider seasonal variation in vitamin D deficiency by conducting multiple measurements of 25(OH)D concentrations whenever possible. Interventions to improve diet and increase physical activity levels may be helpful for reducing vitamin D deficiency. In addition, vitamin D deficiency may be associated with asthma in populations with a high prevalence of deficiency, but studies are needed to determine whether there is a threshold 25(OH)D concentration after which higher vitamin D levels show no benefit. Lastly, future prospective studies and supplementation trials should incorporate measures of free 25(OH)D to explore further associations with pulmonary function and atopy. Thesis advisor: William Checkley, MD, PhD Assistant Professor, International Health Thesis Readers: Nadia N. Hansel, MD, MPH nhansel1@jhmi.edu Associate Professor and Thesis Committee Chair Division of Pulmonary and Critical Care Medicine Johns Hopkins School of Medicine James Tielsch, PhD, MHS Adjunct Professor, International Health Ana Navas-Acien, MD Associate Professor, Environmental Health Sciences Alternate Thesis Readers: Keith West, DrPH Professor, International Health Marie Diener-West, PhD Professor, Biostatistic