Vitamin D Metabolism is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE(2020)
摘要
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 D-3, administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D-3, 25(OH)D-3, and 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25 [OH](2)D-3) 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 1 alpha,25(OH)(2)D-3-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)D-3-to-vitamin D-3 and highermolar ratios of 1 alpha,25(OH)(2)D-3-to-25(OH)D-3 both presupplementation and postsupplementation (P< 0.005). Intergroup differences in 1 alpha,25(OH)(2)D-3-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)D-3-to-vitamin D-3 and increased molar ratios of 1 alpha,25(OH)(2)D-3-to-25(OH)D-3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.
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关键词
vitamin D 25-hydroxylase,vitamin D 1 alpha-hydroxylase,1 alpha,25-dihydroxyvitamin D,24R,25-dihydroxyvitamin D,4,beta 25-dihydroxyvitamin D
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