TY - JOUR AB - RATIONALE: Vitamin D deficiency is common in patients with asthma and COPD. Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions. OBJECTIVE: 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 one year, differed between those with asthma or COPD vs. controls. Serum concentrations of vitamin D3, 25(OH)D3 and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined pre- and post-supplementation 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 fourteen datasets to compare expression of 1α,25[OH]2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD vs. controls. MEASUREMENTS AND MAIN RESULTS: The mean post-supplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in controls (39.8 nmol/L; P=0.001). Compared with controls, 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 pre- and post-supplementation (P≤0.005). Inter-group differences in 1α,25[OH]2D3-inducible gene expression signatures were modest and variable where 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. AU - Jolliffe,DA AU - Stefanidis,C AU - Wang,Z AU - Kermani,NZ AU - Dimitrov,V AU - White,JH AU - McDonough,JE AU - Janssens,W AU - Pfeffer,P AU - Griffiths,CJ AU - Bush,A AU - Guo,Y AU - Christenson,S AU - Adcock,IM AU - Chung,KF AU - Thummel,KE AU - Martineau,AR DO - 10.1164/rccm.201909-1867OC EP - 382 PY - 2020/// SN - 1073-449X SP - 371 TI - Vitamin D metabolism is dysregulated in asthma and chronic obstructive pulmonary disease. T2 - American Journal of Respiratory and Critical Care Medicine UR - http://dx.doi.org/10.1164/rccm.201909-1867OC UR - https://www.ncbi.nlm.nih.gov/pubmed/32186892 UR - https://www.atsjournals.org/doi/10.1164/rccm.201909-1867OC UR - http://hdl.handle.net/10044/1/84755 VL - 202 ER -