Rationale: 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.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 1α,25-dihydroxyvitamin D₃ (1α,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 1α,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 COPD had lower molar ratios of 25(OH)D₃-to-vitamin D₃ and higher molar ratios of 1α,25(OH)₂D₃-to-25(OH)D₃ both presupplementation and postsupplementation (P ≤ 0.005). Intergroup differences in 1α,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 1α,25(OH)₂D₃-to-25(OH)D₃ in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.

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