Vitamin D Metabolism Is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease.

Vitamin D deficiency is common in patients with asthma and chronic obstructive pulmonary disease (COPD). Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions. To determine whether vitamin D metabolism is altered in asthma or COPD. We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D, administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D, 25(OH)D, and 1α,25-dihydroxyvitamin D (1α,25[OH]D) were determined presupplementation and postsupplementation in 93 adults with asthma, COPD, or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed 14 datasets to compare expression of 1α,25(OH)D-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD versus control subjects. The mean postsupplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in control subjects (39.8 nmol/L;  = 0.001). Compared with control subjects, patients with asthma and COPD had lower molar ratios of 25(OH)D-to-vitamin D and higher molar ratios of 1α,25(OH)D-to-25(OH)D both presupplementation and postsupplementation ( ≤ 0.005). Intergroup differences in 1α,25(OH)D-inducible gene expression signatures were modest and variable if statistically significant. Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D-to-vitamin D and increased molar ratios of 1α,25(OH)D-to-25(OH)D in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.