Open AccessVitamin D Metabolism Is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease
Author(s) -
David A. Jolliffe,
Christos Stefanidis,
Zhican Wang,
Nazanin Zounemat Kermani,
V. Dimitrov,
John H. White,
John E. McDonough,
Wim Janssens,
Paul Pfeffer,
Debabrata Bandyopadhyay,
Andrew Bush,
Yike Guo,
Stephanie A. Christenson,
Ian M. Adcock,
Kian Fan Chung,
Kenneth E. Thummel,
Adrian R. Martineau
Publication year - 2020
Publication title -
american journal of respiratory and critical care medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.272
H-Index - 374
eISSN - 1535-4970
pISSN - 1073-449X
DOI - 10.1164/rccm.201909-1867oc
Subject(s) - copd , medicine , asthma , vitamin d and neurology , vitamin , metabolite , pulmonary disease , vitamin d deficiency , endocrinology , gastroenterology
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 1α,25-dihydroxyvitamin D 3 (1α,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 1α,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 COPD had lower molar ratios of 25(OH)D 3 -to-vitamin D 3 and higher molar ratios of 1α,25(OH) 2 D 3 -to-25(OH)D 3 both presupplementation and postsupplementation ( P ≤ 0.005). Intergroup differences in 1α,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 1α,25(OH) 2 D 3 -to-25(OH)D 3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.