TY - JOUR
T1 - Vitamin d metabolism is dysregulated in asthma and chronic obstructive pulmonary disease
AU - Jolliffe, David A.
AU - Stefanidis, Christos
AU - Wang, Zhican
AU - Kermani, Nazanin Z.
AU - Dimitrov, Vassil
AU - White, John H.
AU - McDonough, John E.
AU - Janssens, Wim
AU - Pfeffer, Paul
AU - Griffiths, Christopher J.
AU - Bush, Andrew
AU - GUO, Yi-Ke
AU - Christenson, Stephanie
AU - Adcock, Ian M.
AU - Chung, Kian Fan
AU - Thummel, Kenneth E.
AU - Martineau, Adrian R.
N1 - Funding Information:
Supported by the UK National Institute for Health Research (ref RP-PG-0407-10398), Asthma UK (ref AUK-AC-2012-01), and the U.S. NIH (ref 5R01 GM63666). The views expressed are those of the authors and not necessarily those of the U.K. National Health Service, the NIHR, or the UK or U.S. departments of health.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - 1a
KW - 24R
KW - 25-dihydroxyvitamin D
KW - 4
KW - b25-dihydroxyvitamin D
KW - vitamin D 1a-hydroxylase
KW - vitamin D 25-hydroxylase
UR - https://www.scopus.com/pages/publications/85083982724
U2 - 10.1164/rccm.201909-1867OC
DO - 10.1164/rccm.201909-1867OC
M3 - Journal article
C2 - 32186892
AN - SCOPUS:85083982724
SN - 1073-449X
VL - 202
SP - 371
EP - 382
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 3
ER -
