Department of Pediatrics, Emory University, Atlanta, Ga.
Department of Pediatrics, Emory University, Atlanta, Ga; Department of Biomedical Informatics, Emory University, Atlanta, Ga.
J Allergy Clin Immunol. 2023 Jan;151(1):118-127.e10. doi: 10.1016/j.jaci.2022.07.027. Epub 2022 Sep 9.
The asthma of some children remains poorly controlled, with recurrent exacerbations despite treatment with inhaled corticosteroids. Aside from prior exacerbations, there are currently no reliable predictors of exacerbation-prone asthma in these children and only a limited understanding of the potential underlying mechanisms.
We sought to quantify small molecules in the plasma of children with exacerbation-prone asthma through mass spectrometry-based metabolomics. We hypothesized that the plasma metabolome of these children would differ from that of children with non-exacerbation-prone asthma.
Plasma metabolites were extracted from 4 pediatric asthma cohorts (215 total subjects, with 41 having exacerbation-prone asthma) and detected with a mass spectrometer. High-confidence annotations were retained for univariate analysis and were confirmed by a sensitivity analysis in subjects receiving high-dose inhaled corticosteroids. Metabolites that varied by cohort were excluded. MetaboAnalyst software was used to identify pathways of interest. Concentrations were calculated by reference standardization.
We identified 32 unique, cohort-independent metabolites that differed in children with exacerbation-prone asthma compared to children with non-exacerbation-prone asthma. Comparison of metabolite concentrations to literature-reported values for healthy children revealed that most metabolites were decreased in both asthma groups, but more so in exacerbation-prone asthma. Pathway analysis identified arginine, lysine, and methionine pathways as most impacted.
Several plasma metabolites are perturbed in children with exacerbation-prone asthma and are largely related to arginine, lysine, and methionine pathways. While validation is needed, plasma metabolites may be potential biomarkers for exacerbation-prone asthma in children.
尽管接受吸入皮质类固醇治疗，一些儿童的哮喘仍控制不佳，反复发作。除了先前的加重外，目前这些儿童没有可靠的预测指标来预测易加重哮喘，而且对潜在的潜在机制也只有有限的了解。
我们通过基于质谱的代谢组学方法来定量分析易加重哮喘儿童的血浆中小分子。我们假设这些儿童的血浆代谢组与不易加重哮喘的儿童不同。
从 4 个儿科哮喘队列（总共 215 名受试者，其中 41 名患有易加重哮喘）中提取血浆代谢物，并使用质谱仪进行检测。保留具有高置信度注释的代谢物进行单变量分析，并通过接受高剂量吸入皮质类固醇的受试者的敏感性分析进行确认。排除因队列而异的代谢物。使用 MetaboAnalyst 软件来识别感兴趣的途径。通过参考标准化计算浓度。
我们确定了 32 种独特的、与队列无关的代谢物，这些代谢物在易加重哮喘的儿童中与不易加重哮喘的儿童存在差异。将代谢物浓度与健康儿童的文献报道值进行比较表明，大多数代谢物在两个哮喘组中均降低，但在易加重哮喘组中降低更为明显。途径分析确定精氨酸、赖氨酸和蛋氨酸途径受到的影响最大。
易加重哮喘儿童的几种血浆代谢物受到干扰，并且主要与精氨酸、赖氨酸和蛋氨酸途径有关。虽然需要验证，但血浆代谢物可能是儿童易加重哮喘的潜在生物标志物。
