Oujiang Laboratory, Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China.
J Proteome Res. 2023 Aug 4;22(8):2558-2569. doi: 10.1021/acs.jproteome.2c00788. Epub 2023 Jul 11.
Community-acquired pneumonia (CAP) is a significant threat to human health and the leading cause of acute respiratory distress syndrome (ARDS). We aimed to reveal the metabolic profiling whether can be used for assessing CAP with or without ARDS (nARDS) and therapeutic effects on CAP patients after treatment. Urine samples were collected at the onset and recovery periods, and metabolomics was employed to identify robust biomarkers. 19 metabolites were significantly changed in the ARDS relative to nARDS, mainly involving purines and fatty acids. After treatment, 7 metabolites in the nARDS and 14 in the ARDS were found to be significantly dysregulated, including fatty acids and amino acids. In the validation cohort, we observed that the biomarker panel consisted of ,-dimethylguanosine, 1-methyladenosine, 3-methylguanine, 1-methyladenosine, and uric acid exhibited better AUCs of 0.900 than pneumonia severity index and acute physiology and chronic health evaluation II (APACHE II) scores between the ARDS and nARDS. Combining -phenylalanine, phytosphingosine, and -acetylaspartylglutamate as biomarkers for discriminating the nARDS and ARDS patients after treatment exhibited good AUCs of 0.811 and 0.821, respectively. The metabolic pathway and defined biomarkers may serve as crucial indicators for predicting the development of ARDS in CAP patients and for assessing therapeutic effects.
社区获得性肺炎(CAP)是对人类健康的重大威胁,也是急性呼吸窘迫综合征(ARDS)的主要原因。我们旨在揭示代谢特征是否可用于评估伴有或不伴有 ARDS(nARDS)的 CAP 以及对 CAP 患者治疗后的疗效。在发病期和恢复期采集尿样,并进行代谢组学分析以鉴定稳健的生物标志物。与 nARDS 相比,ARDS 中 19 种代谢物发生显著变化,主要涉及嘌呤和脂肪酸。治疗后,nARDS 中有 7 种代谢物和 ARDS 中有 14 种代谢物被发现显著失调,包括脂肪酸和氨基酸。在验证队列中,我们观察到生物标志物组合包括 -二甲基鸟苷、1-甲基腺苷、3-甲基鸟嘌呤、1-甲基腺苷和尿酸的 AUC 为 0.900,优于肺炎严重指数和急性生理与慢性健康评估 II(APACHE II)评分在 ARDS 和 nARDS 之间的区分。将 -苯丙氨酸、植物鞘氨醇和 -乙酰天门冬氨酸谷氨酸作为区分治疗后 nARDS 和 ARDS 患者的生物标志物,其 AUC 分别为 0.811 和 0.821。代谢途径和定义的生物标志物可作为预测 CAP 患者发生 ARDS 的关键指标,并评估治疗效果。