Vitamin d metabolism is dysregulated in asthma and chronic obstructive pulmonary disease

Rationale: VitaminDdeficiency 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. Objectives: To determine whether vitamin D metabolism is altered in asthma or COPD. Methods: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D3, administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D3, 25(OH)D3, and 1a,25-dihydroxyvitamin D3 (1a,25 [OH]2D3) 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 1a,25(OH)2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD versus control subjects. Measurements and Main Results: 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; P = 0.001). Compared with control subjects, patients with asthma and COPDhad lowermolar ratios of 25(OH)D3-to-vitamin D3 and highermolar ratios of 1a,25(OH)2D3-To-25(OH)D3 both presupplementation and postsupplementation (P0.005). Intergroup differences in 1a,25(OH)2D3-inducible gene expression signatures were modest and variable if statistically significant. Conclusions: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D3-To-vitamin D3 and increased molar ratios of 1a,25(OH)2D3-To-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.