维生素 D 自由浓度与 VIDA 试验中哮喘治疗失败的关系。
Association of free vitamin D concentrations and asthma treatment failures in the VIDA Trial.
机构信息
Nemours Children's Health System, Jacksonville, Florida.
Washington University School of Medicine, St Louis, Missouri.
出版信息
Ann Allergy Asthma Immunol. 2018 Oct;121(4):444-450.e1. doi: 10.1016/j.anai.2018.06.001. Epub 2018 Jun 14.
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.
背景
由于维生素 D 结合蛋白的差异，血清维生素 D 浓度作为维生素 D 状态的生物标志物的使用存在疑问。
目的
确定游离维生素 D3 浓度与接受维生素 D 附加治疗增强哮喘患者皮质激素反应（VIDA）试验的哮喘患者治疗失败和加重率之间的关联。
方法
通过酶联免疫吸附试验直接测量游离浓度，并分为低、中、高组：12 周口服维生素 D3 补充后，游离浓度分别小于 5pg/ml（n=65）、5-9pg/ml（n=84）和大于 9pg/ml（n=48），并与结局相关联。
结果
结局与游离浓度无关：总体治疗失败率分别为 0.60（95%置信区间[CI]0.46-0.78）、0.53（95%CI 0.40-0.70）和 0.69（95%CI 0.54-0.90）/人年（P=0.51）；总体恶化率分别为 0.28（95%CI 0.17-0.48）、0.15（95%CI 0.08-0.30）和 0.42（95%CI 0.27-0.66）/人年（P=0.22）。与非西班牙裔白人和西班牙裔相比，非西班牙裔黑人和西班牙裔的基线游离浓度平均值（标准差）较低：分别为 4.10（1.33）和 4.38（1.11）pg/ml，而非西班牙裔白人的为 5.16（1.65）pg/ml（P<0.001 和 P=0.038）。女性和男性的基线游离浓度平均值（标准差）不同：4.57（1.58）和 5.08（1.41）（P=0.026）；非超重（体重指数[BMI] < 25）和超重（BMI > 25）的游离浓度平均值（标准差）不同：5.45（1.86）和 4.54（1.39）（P<0.001）。游离分数因种族和性别而异，但与 BMI 无关。
结论
在 VIDA 试验参与者中，游离浓度作为维生素 D 补充疗效的生物标志物不如总浓度。未来对哮喘患者维生素 D 状态的研究应同时测量游离和总浓度，以更好地了解哪种维生素 D 功能标志物最具信息性。
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