Association of Free Vitamin D Concentrations and Asthma Treatment Failures in the VIDA Trial

Overview

Journal Ann Allergy Asthma Immunol

Specialties Allergy & Immunology
Pulmonary Medicine

Date 2018 Jun 17

PMID 29908319

Citations 6

Authors

John J Lima

Mario Castro

Tonya S King

Jason E Lang

Victor E Ortega

Stephen P Peters

Loren C Denlinger

Elliot Israel

Christine A Sorkness

Michael E Wechsler

Sally E Wenzel

Lewis J Smith

Affiliations

Soon will be listed here.

Abstract

Background: Use of vitamin D serum concentrations as a biomarker of vitamin D status is questionable because of variation in vitamin D binding protein.

Objective: To determine associations between free vitamin D3 concentrations and rates of treatment failure and exacerbations in patients with asthma participating in the Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma (VIDA) trial.

Methods: Free concentrations were directly measured by enzyme-linked immunosorbent assay and stratified into low, medium, and high groups: less than 5pg/mL (n = 65), 5 to 9pg/mL (n = 84), and greater than 9pg/mL (n = 48) after 12 weeks of supplementation with oral vitamin D3 and associated with outcomes.

Results: Outcomes did not associate with free concentrations: overall treatment failure rates were 0.60 (95% confidence interval [CI] 0.46-0.78), 0.53 (95%CI 0.40- 0.70), and 0.69 (95%CI 0.54-0.90)/person-year (P = .51), respectively; overall exacerbation rates were 0.28 (95%CI 0.17-0.48), 0.15 (95%CI 0.08-0.30) and 0.42 (95%CI 0.27-0.66)/person-year (P = .22). Mean (standard deviation) baseline free concentrations were lower in non-Hispanic blacks and Hispanics compared with non-Hispanic whites: 4.10 (1.33) and 4.38 (1.11) pg/mL vs 5.16 (1.65) pg/ml, (P < .001 and P = 0.038), respectively. Mean (standard deviation) baseline free concentrations differed between females and males: 4.57 (1.58) and 5.08 (1.41) (P = .026); and between non-overweight (body mass index [BMI] < 25) and overweight (BMI > 25): 5.45 (1.86) vs 4.54 (1.39) (P < .001). The free fraction differed by race and sex but not by BMI.

Conclusion: The use of free concentrations was inferior to total concentrations as a biomarker of efficacy of vitamin D supplementation in VIDA trial participants. Future studies of vitamin D status in patients with asthma should measure both free and total concentrations to better understand which marker of vitamin D function is most informative.

Citing Articles

Therapeutic Potential of Vitamin D in Management of Asthma: A Literature Review.

Tibrewal C, Modi N, Bajoria P, Dave P, Rohit R, Patel P Cureus. 2023; 15(7):e41956.

PMID: 37588324 PMC: 10425698. DOI: 10.7759/cureus.41956.

Development of free 25-hydroxyvitamin D3 assay method using liquid chromatography-tandem mass spectrometry.

Ishimine N, Wu S, Ota R, Takahashi K, Takiwaki M, Sugano M Biosci Rep. 2022; 42(10).

PMID: 36107130 PMC: 9547169. DOI: 10.1042/BSR20221326.

Asthma and Vitamin D Deficiency: Occurrence, Immune Mechanisms, and New Perspectives.

Salmanpour F, Kian N, Samieefar N, Tabari M, Rezaei N J Immunol Res. 2022; 2022:6735900.

PMID: 35874901 PMC: 9307373. DOI: 10.1155/2022/6735900.

Vitamin D Binding Protein and the Biological Activity of Vitamin D.

Chun R, Shieh A, Gottlieb C, Yacoubian V, Wang J, Hewison M Front Endocrinol (Lausanne). 2019; 10:718.

PMID: 31708871 PMC: 6821678. DOI: 10.3389/fendo.2019.00718.

Vitamin D binding protein is not affected by high-dose vitamin D supplementation: a post hoc analysis of a randomised, placebo-controlled study.

Bjorkhem-Bergman L, Torefalk E, Ekstrom L, Bergman P BMC Res Notes. 2018; 11(1):619.

PMID: 30157946 PMC: 6114541. DOI: 10.1186/s13104-018-3725-7.

References

Castro M, King T, Kunselman S, Cabana M, Denlinger L, Holguin F . Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA. 2014; 311(20):2083-91. PMC: 4217655. DOI: 10.1001/jama.2014.5052. View

Looker A, Pfeiffer C, Lacher D, Schleicher R, Picciano M, Yetley E . Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004. Am J Clin Nutr. 2008; 88(6):1519-27. PMC: 2745830. DOI: 10.3945/ajcn.2008.26182. View

Hill T, Graham L, Divgi V . Racial disparities in pediatric asthma: a review of the literature. Curr Allergy Asthma Rep. 2010; 11(1):85-90. DOI: 10.1007/s11882-010-0159-2. View

Batai K, Murphy A, Shah E, Ruden M, Newsome J, Agate S . Common vitamin D pathway gene variants reveal contrasting effects on serum vitamin D levels in African Americans and European Americans. Hum Genet. 2014; 133(11):1395-405. PMC: 4185105. DOI: 10.1007/s00439-014-1472-y. View

Zhang M, Zhao L, Zhou Y, Badr R, Watson P, Ye A . SNP rs11185644 of RXRA gene is identified for dose-response variability to vitamin D3 supplementation: a randomized clinical trial. Sci Rep. 2017; 7:40593. PMC: 5228186. DOI: 10.1038/srep40593. View

Mendel C . The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev. 1989; 10(3):232-74. DOI: 10.1210/edrv-10-3-232. View

Yousefzadeh P, Shapses S, Wang X . Vitamin D Binding Protein Impact on 25-Hydroxyvitamin D Levels under Different Physiologic and Pathologic Conditions. Int J Endocrinol. 2014; 2014:981581. PMC: 4020458. DOI: 10.1155/2014/981581. View

Martineau A, Cates C, Urashima M, Jensen M, Griffiths A, Nurmatov U . Vitamin D for the management of asthma. Cochrane Database Syst Rev. 2016; 9:CD011511. PMC: 6457769. DOI: 10.1002/14651858.CD011511.pub2. View

Man L, Zhang Z, Zhang M, Zhang Y, Li J, Zheng N . Association between vitamin D deficiency and insufficiency and the risk of childhood asthma: evidence from a meta-analysis. Int J Clin Exp Med. 2015; 8(4):5699-706. PMC: 4483990. View

10.

Ahn J, Yu K, Stolzenberg-Solomon R, Simon K, McCullough M, Gallicchio L . Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 2010; 19(13):2739-45. PMC: 2883344. DOI: 10.1093/hmg/ddq155. View

11.

Lai J, Bikle D, Lizaola B, Hayssen H, Terrault N, Schwartz J . Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in cirrhotics with and without synthetic dysfunction. Liver Int. 2015; 35(10):2294-300. PMC: 4567539. DOI: 10.1111/liv.12819. View

12.

LeFevre M . Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014; 162(2):133-40. DOI: 10.7326/M14-2450. View

13.

Hoofnagle A, Eckfeldt J, Lutsey P . Vitamin D-Binding Protein Concentrations Quantified by Mass Spectrometry. N Engl J Med. 2015; 373(15):1480-2. PMC: 4654614. DOI: 10.1056/NEJMc1502602. View

14.

Sutherland E, Goleva E, Jackson L, Stevens A, Leung D . Vitamin D levels, lung function, and steroid response in adult asthma. Am J Respir Crit Care Med. 2010; 181(7):699-704. PMC: 2868500. DOI: 10.1164/rccm.200911-1710OC. View

15.

Johnsen M, Grimnes G, Figenschau Y, Torjesen P, Almas B, Jorde R . Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D. Scand J Clin Lab Invest. 2014; 74(3):177-83. DOI: 10.3109/00365513.2013.869701. View

16.

Powe C, Ricciardi C, Berg A, Erdenesanaa D, Collerone G, Ankers E . Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res. 2011; 26(7):1609-16. PMC: 3351032. DOI: 10.1002/jbmr.387. View

17.

Walsh J, Evans A, Bowles S, Naylor K, Jones K, Schoenmakers I . Free 25-hydroxyvitamin D is low in obesity, but there are no adverse associations with bone health. Am J Clin Nutr. 2016; 103(6):1465-71. DOI: 10.3945/ajcn.115.120139. View

18.

Freishtat R, Iqbal S, Pillai D, Klein C, Ryan L, Benton A . High prevalence of vitamin D deficiency among inner-city African American youth with asthma in Washington, DC. J Pediatr. 2010; 156(6):948-952. PMC: 3328513. DOI: 10.1016/j.jpeds.2009.12.033. View

19.

Bikle D, Gee E, Halloran B, Kowalski M, Ryzen E, Haddad J . Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986; 63(4):954-9. DOI: 10.1210/jcem-63-4-954. View

20.

Pludowski P, Holick M, Grant W, Konstantynowicz J, Mascarenhas M, Haq A . Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol. 2017; 175:125-135. DOI: 10.1016/j.jsbmb.2017.01.021. View