哮喘和慢性阻塞性肺疾病中的维生素D代谢异常
2020/04/07
摘要
理论及依据：哮喘和COPD患者常见维生素D缺乏。低水平的25-羟基维生素D（25 [OH] D）可能是这些情况的病因或结果。
目的：明确哮喘或COPD中维生素D代谢是否发生改变。
方法：我们在186位成年人中进行了一项纵向研究，以确定在一年内6次口服3 mg维生素D3后25（OH）D水平变化在哮喘或COPD患者与对照组之间是否存在差异。在93名哮喘、COPD或无病情患者中，确定给药前后的维生素D3、25（OH）D3和1α，25-二羟基维生素D3（1α，25 [OH] 2D3）的血清浓度，同时比较各组之间代谢物与母体化合物摩尔比，以评估羟化酶活性。此外，我们分析了14个数据集，从哮喘、COPD的成年人与对照组中获得临床样品，以比较1α，25 [OH] 2D3诱导型基因表达的特征。
测量及主要结果：哮喘（20.9nmol/L）和COPD患者（21.5nmol/L）补充后的25（OH）D增加水平低于对照组（39.8 nmol/L；P=0.001）。 与对照组相比，哮喘和慢性阻塞性肺病患者在治疗前后均具有较低的25（OH）D3维生素D3摩尔比较低、1α，25（OH）2D3与25（OH）D3摩尔比较高（P≤0.005）。1α，25 [OH] 2D3诱导型基因表达特征的组间差异适度且在统计学上具有显著差异。
结论：哮喘和COPD患者补充维生素D后较低25（OH）D水平、25（OH）D3/维生素D3的摩尔比降低及1α，25（OH）2D3/25（OH）D3水平升高，表明在这些情况下维生素D代谢调节的失衡。
Vitamin D Metabolism is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease.
Jolliffe DA1, Stefanidis C1, Wang Z2, Kermani NZ3, Dimitrov V4, White JH5, McDonough JE6, Janssens W7, Pfeffer P8, Griffiths CJ9, Bush A10, Guo Y3, Christenson S11, Adcock IM12, Chung KF13, Thummel KE2, Martineau AR14.
Abstract
RATIONALE:Vitamin D deficiency is common in patients with asthma and COPD. Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions.
OBJECTIVE: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 one year, differed between those with asthma or COPD vs. controls. Serum concentrations of vitamin D3, 25(OH)D3 and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined pre- and post-supplementation 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 fourteen datasets to compare expression of 1α,25[OH]2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD vs. controls.
MEASUREMENTS AND MAIN RESULTS:The mean post-supplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in controls (39.8 nmol/L; P=0.001). Compared with controls, 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 pre- and post-supplementation (P≤0.005). Inter-group differences in 1α,25[OH]2D3-inducible gene expression signatures were modest and variable where 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.
理论及依据：哮喘和COPD患者常见维生素D缺乏。低水平的25-羟基维生素D（25 [OH] D）可能是这些情况的病因或结果。
目的：明确哮喘或COPD中维生素D代谢是否发生改变。
方法：我们在186位成年人中进行了一项纵向研究，以确定在一年内6次口服3 mg维生素D3后25（OH）D水平变化在哮喘或COPD患者与对照组之间是否存在差异。在93名哮喘、COPD或无病情患者中，确定给药前后的维生素D3、25（OH）D3和1α，25-二羟基维生素D3（1α，25 [OH] 2D3）的血清浓度，同时比较各组之间代谢物与母体化合物摩尔比，以评估羟化酶活性。此外，我们分析了14个数据集，从哮喘、COPD的成年人与对照组中获得临床样品，以比较1α，25 [OH] 2D3诱导型基因表达的特征。
测量及主要结果：哮喘（20.9nmol/L）和COPD患者（21.5nmol/L）补充后的25（OH）D增加水平低于对照组（39.8 nmol/L；P=0.001）。 与对照组相比，哮喘和慢性阻塞性肺病患者在治疗前后均具有较低的25（OH）D3维生素D3摩尔比较低、1α，25（OH）2D3与25（OH）D3摩尔比较高（P≤0.005）。1α，25 [OH] 2D3诱导型基因表达特征的组间差异适度且在统计学上具有显著差异。
结论：哮喘和COPD患者补充维生素D后较低25（OH）D水平、25（OH）D3/维生素D3的摩尔比降低及1α，25（OH）2D3/25（OH）D3水平升高，表明在这些情况下维生素D代谢调节的失衡。
（中日友好医院呼吸与危重症医学科 张鑫 摘译 林江涛 审校）
（Am J Respir Crit Care Med. 2020 Mar 18. doi: 10.1164/rccm.201909-1867OC. [Epub ahead of print]）
（Am J Respir Crit Care Med. 2020 Mar 18. doi: 10.1164/rccm.201909-1867OC. [Epub ahead of print]）
Vitamin D Metabolism is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease.
Jolliffe DA1, Stefanidis C1, Wang Z2, Kermani NZ3, Dimitrov V4, White JH5, McDonough JE6, Janssens W7, Pfeffer P8, Griffiths CJ9, Bush A10, Guo Y3, Christenson S11, Adcock IM12, Chung KF13, Thummel KE2, Martineau AR14.
Abstract
RATIONALE:Vitamin D deficiency is common in patients with asthma and COPD. Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions.
OBJECTIVE: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 one year, differed between those with asthma or COPD vs. controls. Serum concentrations of vitamin D3, 25(OH)D3 and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined pre- and post-supplementation 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 fourteen datasets to compare expression of 1α,25[OH]2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD vs. controls.
MEASUREMENTS AND MAIN RESULTS:The mean post-supplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in controls (39.8 nmol/L; P=0.001). Compared with controls, 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 pre- and post-supplementation (P≤0.005). Inter-group differences in 1α,25[OH]2D3-inducible gene expression signatures were modest and variable where 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.
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