L-Arginine supplementation in severe asthma
L-Arginine supplementation in severe asthma
复制标题
L-精氨酸补充治疗重症哮喘
DOI：
10.1172/jci.insight.137777
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发表时间：
2020-07-09
期刊：
影响因子：
8
通讯作者：
Kenyon, Nicholas J.
中科院分区：
文献类型：
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作者：
Liao, Shu-Yi;Showalter, Megan R.;Kenyon, Nicholas J.
背景资料。L-精氨酸代谢紊乱被认为发生在重症哮喘患者中。补充L精氨酸对这些患者L精氨酸代谢产物谱的影响尚不清楚。我们假设，与安慰剂相比，患有低呼出一氧化氮(FeNO)的重症哮喘患者在其标准哮喘药物中加入L-精氨酸后，病情恶化的程度会更少，并将表现出最大的代谢物谱变化。方法：参与者参加了UCD的单中心、交叉、双盲L-精氨酸干预试验。受试者服用安慰剂或L精氨酸，剂量为0.05 mg/kg(理想体重)，每天两次。主要终点是中度哮喘加重。用质谱仪测定纵向血浆代谢物水平。采用线性混合效应模型检验治疗效果。结果：纳入50名研究对象。在总体队列中，L-精氨酸并没有显著减少哮喘的恶化。更高的瓜氨酸水平和更低的精氨酸利用率指数与更高的FeNO水平相关(分别为P=0.005和P=2.51×10(-9))。较高的AAI与较低的恶化事件相关。二十烷类前列腺素H-2(PGH(2))和N-α-乙酰-L-精氨酸被发现是区分临床有效和无效的良好预测指标。结论：在L-精氨酸干预的总体队列中，哮喘恶化的发生率没有统计学意义的降低。PGH(2)、N-α-乙酰-L-精氨酸和AAI可作为未来干预精氨酸代谢组的临床试验的预测生物标志物。
BACKGROUND. Dysregulation of L-arginine metabolism has been proposed to occur in patients with severe asthma. The effects of L-arginine supplementation on L-arginine metabolite profiles in these patients are unknown. We hypothesized that individuals with severe asthma with low fractional exhaled nitric oxide (FeNO) would have fewer exacerbations with the addition of L-arginine to their standard asthma medications compared with placebo and would demonstrate the greatest changes in metabolite profiles.METHODS. Participants were enrolled in a single-center, crossover, double-blind L-arginine intervention trial at UCD. Subjects received placebo or L-arginine, dosed orally at 0.05 mg/kg (ideal body weight) twice daily. The primary end point was moderate asthma exacerbations. Longitudinal plasma metabolite levels were measured using mass spectrometry. A linear mixed-effect model with subject-specific intercepts was used for testing treatment effects.RESULTS. A cohort of 50 subjects was included in the final analysis. L-Arginine did not significantly decrease asthma exacerbations in the overall cohort. Higher citrulline levels and a lower arginine availability index (AAI) were associated with higher FeNO (P = 0.005 and P = 2.51 x 10(-9), respectively). Higher AAI was associated with lower exacerbation events. The eicosanoid prostaglandin H-2 (PGH(2)) and N-alpha-acetyl-L-arginine were found to be good predictors for differentiating clinical responders and nonresponders.CONCLUSIONS. There was no statistically significant decrease in asthma exacerbations in the overall cohort with L-arginine intervention. PGH(2), N-alpha-acetyl-L-arginine, and the AAI could serve as predictive biomarkers in future clinical trials that intervene in the arginine metabolome.