Pharmaco-Metabolomics of Inhaled Corticosteroid Response in Individuals with Asthma.
Pharmaco-Metabolomics of Inhaled Corticosteroid Response in Individuals with Asthma.
复制标题
DOI：
10.3390/jpm11111148
复制
发表时间：
2021-11-04
影响因子：
--
通讯作者：
Lasky-Su JA
中科院分区：
文献类型：
--
作者：
Kachroo P;Sordillo JE;Lutz SM;Weiss ST;Kelly RS;McGeachie MJ;Wu AC;Lasky-Su JA
哮喘治疗反应的代谢组学指标尚未确定。在这项研究中，我们旨在揭示吸入皮质类固醇（ICS）治疗时与哮喘加重相关的血浆代谢组学特征。我们确定这些特征是否会随着从青春期到成年期的年龄而变化。我们利用来自麻省总医院布里格姆生物样本库的170名接受ICS治疗的哮喘患者的数据，确定与ICS治疗时哮喘加重相关的血浆代谢物，并检查代谢物加重关联随年龄变化的潜在影响。我们使用液相色谱-高分辨率质谱为基础的代谢组学分析。性别分层分析也进行了显著的关联。研究对象年龄13 ~ 43岁，平均年龄33.5岁。在测试的783种内源性代谢物中，经过多次比较校正和潜在混杂因素校正（Bonferroni p值< 6.2 × 10−4），8种代谢物显示出与病情恶化的显著关联。脂肪酸代谢物的潜在影响被性别所改变，男性的代谢物水平随着ICS的恶化而下降得更大。38种代谢物表现出与年龄的相互作用（名义p值< 0.05）。我们的研究结果表明，血浆代谢组学特征不同于服用ICS时哮喘发作的个体。分化代谢物可以作为ICS反应的生物标志物，并可能突出ICS反应变异性的代谢途径。
Metabolomic indicators of asthma treatment responses have yet to be identified. In this study, we aimed to uncover plasma metabolomic profiles associated with asthma exacerbations while on inhaled corticosteroid (ICS) treatment. We determined whether these profiles change with age from adolescence to adulthood. We utilized data from 170 individuals with asthma on ICS from the Mass General Brigham Biobank to identify plasma metabolites associated with asthma exacerbations while on ICS and examined potential effect modification of metabolite-exacerbation associations by age. We used liquid chromatography–high-resolution mass spectrometry-based metabolomic profiling. Sex-stratified analyses were also performed for the significant associations. The age range of the participating individuals was 13–43 years with a mean age of 33.5 years. Of the 783 endogenous metabolites tested, eight demonstrated significant associations with exacerbation after correction for multiple comparisons and adjusting for potential confounders (Bonferroni p value < 6.2 × 10−4). Potential effect modification by sex was detected for fatty acid metabolites, with males showing a greater reduction in their metabolite levels with ICS exacerbation. Thirty-eight metabolites showed suggestive interactions with age on exacerbation (nominal p-value < 0.05). Our findings demonstrate that plasma metabolomic profiles differ for individuals who experience asthma exacerbations while on ICS. The differentiating metabolites may serve as biomarkers of ICS response and may highlight metabolic pathways underlying ICS response variability.