Association of free vitamin D3 concentrations and asthma treatment failures in the VIDA Trial

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

doi:10.1016/j.anai.2018.06.001

Association of free vitamin D₃ concentrations and asthma treatment failures in the VIDA Trial

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

^*Corresponding author for this work

Medicine, Pulmonary Division

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Background: Use of vitamin D₃ 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 5 pg/ mL (n = 65), 5 to 9 pg/ mL (n = 84), and greater than 9 pg/ 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 D₃ 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.

Original language	English (US)
Pages (from-to)	444-450.e1
Journal	Annals of Allergy, Asthma and Immunology
Volume	121
Issue number	4
DOIs	https://doi.org/10.1016/j.anai.2018.06.001
State	Published - Oct 2018

Funding

Funding Sources: This study was conducted with the support of grants HL098102, U10HL098096, UL1TR000150, UL1TR000430, UL1TR000050, HL098075, UL1TR001082, HL098090, HL098177, UL1TR000439, HL098098, UL1TR000448, HL098107, HL098112, HL098103, UL1TR000454, and HL098115 that were awarded by the National Heart, Lung, and Blood Institute. Ciclesonide and levalbuterol were provided without cost by Sunovion Pharmaceuticals Inc.

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Immunology and Allergy
Immunology

Access to Document

10.1016/j.anai.2018.06.001

Cite this

Lima, J. J., Castro, M., King, T. S., Lang, J. E., Ortega, V. E., Peters, S. P., Denlinger, L. C., Israel, E., Sorkness, C. A., Wechsler, M. E., Wenzel, S. E., & Smith, L. J. (2018). Association of free vitamin D₃ concentrations and asthma treatment failures in the VIDA Trial. Annals of Allergy, Asthma and Immunology, 121(4), 444-450.e1. https://doi.org/10.1016/j.anai.2018.06.001

@article{88327ef226ef4d429c14f448dc102853,

title = "Association of free vitamin D3 concentrations and asthma treatment failures in the VIDA Trial",

abstract = "Background: Use of vitamin D3 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 5 pg/ mL (n = 65), 5 to 9 pg/ mL (n = 84), and greater than 9 pg/ 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 D3 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.",

author = "Lima, {John J.} and Mario Castro and King, {Tonya S.} and Lang, {Jason E.} and Ortega, {Victor E.} and Peters, {Stephen P.} and Denlinger, {Loren C.} and Elliot Israel and Sorkness, {Christine A.} and Wechsler, {Michael E.} and Wenzel, {Sally E.} and Smith, {Lewis J.}",

note = "Publisher Copyright: {\textcopyright} 2018 American College of Allergy, Asthma 8 Immunology",

year = "2018",

month = oct,

doi = "10.1016/j.anai.2018.06.001",

language = "English (US)",

volume = "121",

pages = "444--450.e1",

journal = "Annals of Allergy, Asthma and Immunology",

issn = "1081-1206",

publisher = "American College of Allergy, Asthma and Immunology",

number = "4",

}

TY - JOUR

T1 - Association of free vitamin D3 concentrations and asthma treatment failures in the VIDA Trial

AU - Lima, John J.

AU - Castro, Mario

AU - King, Tonya S.

AU - Lang, Jason E.

AU - Ortega, Victor E.

AU - Peters, Stephen P.

AU - Denlinger, Loren C.

AU - Israel, Elliot

AU - Sorkness, Christine A.

AU - Wechsler, Michael E.

AU - Wenzel, Sally E.

AU - Smith, Lewis J.

PY - 2018/10

Y1 - 2018/10

N2 - Background: Use of vitamin D3 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 5 pg/ mL (n = 65), 5 to 9 pg/ mL (n = 84), and greater than 9 pg/ 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 D3 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.

AB - Background: Use of vitamin D3 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 5 pg/ mL (n = 65), 5 to 9 pg/ mL (n = 84), and greater than 9 pg/ 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 D3 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.

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