David A Jolliffe1, Christos Stefanidis1, Zhican Wang2, Nazanin Z Kermani3, Vassil Dimitrov4, John H White4, John E McDonough5, Wim Janssens6, Paul Pfeffer1, Christopher J Griffiths1, Andrew Bush7, Yike Guo3, Stephanie Christenson8, Ian M Adcock7, Kian Fan Chung7, Kenneth E Thummel2, Adrian R Martineau1. 1. Asthma UK Centre for Applied Research, Institute of Population Health Sciences, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. 2. Department of Pharmaceutics, University of Washington, Seattle, Washington. 3. Data Science Institute, William Penney Laboratory and. 4. Department of Physiology, McGill University, Montreal, Quebec, Canada. 5. Yale School of Medicine, New Haven, Connecticut. 6. Laboratory of Respiratory Diseases and Thoracic Surgery, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Leuven, Belgium; and. 7. National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom. 8. Division of Pulmonary, Critical Care, Allergy, & Sleep Medicine, Department of Medicine, University of California, San Francisco, California.
Abstract
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 D3, administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D3, 25(OH)D3, and 1α,25-dihydroxyvitamin D3 (1α,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 1α,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 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 presupplementation and postsupplementation (P ≤ 0.005). Intergroup differences in 1α,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 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.
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 D3, administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D3, 25(OH)D3, and 1α,25-dihydroxyvitamin D3 (1α,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 1α,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 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 presupplementation and postsupplementation (P ≤ 0.005). Intergroup differences in 1α,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 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.
Entities:
Keywords:
1α,25-dihydroxyvitamin D; 24R,25-dihydroxyvitamin D; 4,β25-dihydroxyvitamin D; vitamin D 1α-hydroxylase; vitamin D 25-hydroxylase
Authors: Kristina M DiFranco; Jennifer K Mulligan; Aman S Sumal; Gill Diamond Journal: J Steroid Biochem Mol Biol Date: 2017-01-24 Impact factor: 4.292
Authors: Robert J Freishtat; Sabah F Iqbal; Dinesh K Pillai; Catherine J Klein; Leticia M Ryan; Angela S Benton; Stephen J Teach Journal: J Pediatr Date: 2010-03-16 Impact factor: 4.406
Authors: Prescott G Woodruff; Homer A Boushey; Gregory M Dolganov; Chris S Barker; Yee Hwa Yang; Samantha Donnelly; Almut Ellwanger; Sukhvinder S Sidhu; Trang P Dao-Pick; Carlos Pantoja; David J Erle; Keith R Yamamoto; John V Fahy Journal: Proc Natl Acad Sci U S A Date: 2007-09-26 Impact factor: 11.205
Authors: Dave Singh; Steven M Fox; Ruth Tal-Singer; Stewart Bates; John H Riley; Bartolome Celli Journal: PLoS One Date: 2014-09-29 Impact factor: 3.240
Authors: Matthew J Loza; Ratko Djukanovic; Kian Fan Chung; Daniel Horowitz; Keying Ma; Patrick Branigan; Elliot S Barnathan; Vedrana S Susulic; Philip E Silkoff; Peter J Sterk; Frédéric Baribaud Journal: Respir Res Date: 2016-12-15
Authors: Despoina Manousaki; Lavinia Paternoster; Marie Standl; Miriam F Moffatt; Martin Farrall; Emmanuelle Bouzigon; David P Strachan; Florence Demenais; Mark Lathrop; William O C M Cookson; J Brent Richards Journal: PLoS Med Date: 2017-05-09 Impact factor: 11.069
Authors: Nasser M Al-Daghri; Omar S Al-Attas; Sobhy M Yakout; Abdullah M Alnaami; Kaiser Wani; Majed S Alokail Journal: Medicine (Baltimore) Date: 2018-09 Impact factor: 1.817
Authors: Jose Manuel Quesada-Gomez; José Lopez-Miranda; Marta Entrenas-Castillo; Antonio Casado-Díaz; Xavier Nogues Y Solans; José Luis Mansur; Roger Bouillon Journal: Nutrients Date: 2022-06-29 Impact factor: 6.706
Authors: Andrew J Halayko; Christopher D Pascoe; Jessica D Gereige; Michael C Peters; Robyn T Cohen; Prescott G Woodruff Journal: Am J Respir Crit Care Med Date: 2021-08-15 Impact factor: 21.405
Authors: Christos Stefanidis; Andrew Bush; Christopher Newby; Chinedu Nwokoro; Susan Liebeschuetz; Imogen P Skene; Christopher J Griffiths; Adrian R Martineau Journal: ERJ Open Res Date: 2022-05-16
Authors: Zahra Raisi-Estabragh; Adrian R Martineau; Elizabeth M Curtis; Rebecca J Moon; Andrea Darling; Susan Lanham-New; Kate A Ward; Cyrus Cooper; Patricia B Munroe; Steffen E Petersen; Nicholas C Harvey Journal: Aging Clin Exp Res Date: 2021-06-12 Impact factor: 3.636
Authors: Christian Muschitz; Ralf Harun Zwick; Judith Haschka; Hans Peter Dimai; Martina Rauner; Karin Amrein; Robert Wakolbinger; Peter Jaksch; Ernst Eber; Peter Pietschmann Journal: Wien Klin Wochenschr Date: 2021-06-16 Impact factor: 1.704
Authors: Juan F Alcala-Diaz; Laura Limia-Perez; Ricardo Gomez-Huelgas; Maria D Martin-Escalante; Begoña Cortes-Rodriguez; Jose L Zambrana-Garcia; Marta Entrenas-Castillo; Ana I Perez-Caballero; Maria D López-Carmona; Javier Garcia-Alegria; Aquiles Lozano Rodríguez-Mancheño; Maria Del Sol Arenas-de Larriva; Luis M Pérez-Belmonte; Irwin Jungreis; Roger Bouillon; Jose Manual Quesada-Gomez; Jose Lopez-Miranda Journal: Nutrients Date: 2021-05-21 Impact factor: 5.717