PDF(Pubmed)
Abstract：
Preschool children with recurrent wheezing are a heterogeneous population with many underlying biological pathways that contribute to clinical presentations. Although the morbidity of recurrent wheezing in preschool children is significant, biological studies in this population remain quite limited. To address this gap, this study performed untargeted plasma metabolomic analyses in 68 preschool children with recurrent wheezing to identify metabolomic endotypes of wheezing. K-means cluster analysis was performed on metabolomic dataset including a total of 1382 named and unnamed metabolites. We identified three metabolomic clusters which differed in symptom severity, exacerbation occurrence, and variables associated with social disadvantage. Metabolites that distinguished the clusters included those involved in fatty acid metabolism, fatty acids (long chain monounsaturated fatty acids, long chain polyunsaturated fatty acids, and long chain saturated fatty acids), lysophospholipids, phosphatidylcholines, and phosphatidylethanolamines. Pathway analyses identified pathways of interest in each cluster, including steroid metabolism, histidine metabolism, sphingomyelins, and sphingosines, among others. This study highlights the biologic complexity of recurrent wheezing in preschool children and offers novel metabolites and pathways that may be amenable to future study and intervention.
摘要：
反复喘息的学龄前儿童是一个异质性人群，具有许多潜在的生物学途径，有助于临床表现。尽管学龄前儿童反复喘息的发病率很高，该人群的生物学研究仍然非常有限。为了解决这个差距，这项研究对68例反复喘息的学龄前儿童进行了非靶向血浆代谢组学分析,以确定喘息的代谢组学基因型.对包括总共1382个命名和未命名代谢物的代谢组学数据集进行K-均值聚类分析。我们确定了症状严重程度不同的三个代谢组学簇，恶化发生，以及与社会劣势相关的变量。区分簇的代谢物包括参与脂肪酸代谢的那些，脂肪酸（长链单不饱和脂肪酸，长链多不饱和脂肪酸，和长链饱和脂肪酸)，溶血磷脂，磷脂酰胆碱,和磷脂酰乙醇胺。路径分析确定了每个集群中感兴趣的路径，包括类固醇代谢，组氨酸代谢，鞘磷脂,和鞘氨,在其他人中。这项研究强调了学龄前儿童反复喘息的生物学复杂性，并提供了新的代谢产物和途径，可能适合未来的研究和干预。
