Department of Paediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Key Laboratory of Paediatric Respiratory Disease, Institute of Paediatrics, Nanjing University of Chinese Medicine, Nanjing, China.
Respirology. 2019 Jun;24(6):572-581. doi: 10.1111/resp.13479. Epub 2019 Feb 14.
Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology.
Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes.
We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma.
Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.
哮喘是一个全球性的问题，也是一种复杂的疾病，适合进行代谢组学分析。本研究旨在探索儿童哮喘特有的候选生物标志物，并深入了解哮喘的病理生理学机制。
纳入符合健康对照（n=29）、未控制哮喘（n=37）或控制哮喘（n=43）标准的儿童（6-11 岁）。对患儿的尿液样本进行气相色谱-质谱分析，以探讨儿童哮喘中不同类型的代谢谱。此外，我们采用综合策略来阐明有显著差异的代谢物与哮喘相关基因之间的关系。
共鉴定出 51 种差异代谢物，主要与氨基酸、碳水化合物和嘌呤代谢功能障碍有关。包括尿酸、硬脂酸、苏糖醇、乙酰半乳糖胺、十七烷酸、天冬氨酸、黄嘌呤核苷和次黄嘌呤在内的 8 种候选代谢物的组合（调整 P < 0.05，倍数变化 >1.5 或 <0.67），对哮喘的存在和不良控制或良好控制哮喘的区分具有出色的判别性能，且在各组中的曲线下面积均>0.97。基于这些靶点的富集分析表明，Fc 受体、细胞内甾体激素受体信号通路、DNA 损伤和成纤维细胞增殖与儿童哮喘的炎症、免疫和应激相关的生物学进展有关。
对患儿尿液进行代谢组学分析并结合网络生物学方法，可以根据代谢模式对哮喘谱和亚型进行区分。研究结果为儿童哮喘的潜在发病机制提供了新的见解。
