Vitamin d metabolism is dysregulated in asthma and chronic obstructive pulmonary disease

David A. Jolliffe, Christos Stefanidis, Zhican Wang, Nazanin Z. Kermani, Vassil Dimitrov, John H. White, John E. McDonough, Wim Janssens, Paul Pfeffer, Christopher J. Griffiths, Andrew Bush, Yi-Ke GUO, Stephanie Christenson, Ian M. Adcock, Kian Fan Chung, Kenneth E. Thummel, Adrian R. Martineau*

*Corresponding author for this work

    Research output: Contribution to journalJournal articlepeer-review

    50 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)371-382
    Number of pages12
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume202
    Issue number3
    DOIs
    Publication statusPublished - 1 Aug 2020

    Scopus Subject Areas

    • Pulmonary and Respiratory Medicine
    • Critical Care and Intensive Care Medicine

    User-Defined Keywords

    • 1a
    • 24R
    • 25-dihydroxyvitamin D
    • 4
    • b25-dihydroxyvitamin D
    • vitamin D 1a-hydroxylase
    • vitamin D 25-hydroxylase

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