Community-acquired pneumonia (CAP) is the leading cause of lower respiratory tract infections in children. Heat syndrome (HS) and cold syndrome (CS) are two main syndrome types of pediatric CAP in traditional Chinese medicine (TCM). This study aimed to identify plasma metabolic profiles in pediatric CAP and to further select potential biomarkers to distinguish between HS and CS. An ultra-performance liquid chromatography coupled with linear ion trap quadrupole-orbitrap mass spectrometry method was applied to plasma samples of 296 patients and 55 healthy controls (HC). The samples were divided into the discovery group (n = 213, HS = 160, CS = 23, HC = 30) and the validation group (n = 138, HS = 93, CS = 20, HC = 25). The orthogonal partial least-squares discriminant analysis, the value of fold change, and Kruskal-Wallis test with false discovery rate correction (q-value <0.05) were applied to identify differential plasma metabolites. The area under the ROC curve (AUC) was used to evaluate the diagnostic performance of the screened metabolites. The results showed that the plasma levels of aspartic acid, phenylalanine, arginine, lysoPC20:1, lysoPE16:0, lysoPE18:0, and PE (16:0_22:6) were increased in CS compared with HC. The plasma levels of PC (18:1_18:1), PC (20:4_20:4), PE (16:0_18:2), lysoPE20:4, lysoPE18:2, and lysoPE22:6 were decreased, whereas, the plasma level of ceramide (d18:1_24:1) was increased in HS compared with HC. There were 13 differential metabolites in CS (AUC = 0.995) and 15 differential metabolites in HS (AUC = 0.954), compared with HC. A panel of seven biomarkers, including LysoPC20:1, lysoPE16:0, lysoPE18:2, lysoPE20:4, lysoPE22:6, PC (18:1_18:1), and PC (20:4_20:4) showed good discrimination between HS and CS with an AUC of 0.982. Altered plasma amino acids and lipids may provide an objective basis for TCM syndrome differentiation in pediatric CAP.
社区获得性肺炎是儿童最常见的下呼吸道感染性疾病之一,其中医辨证分型可分为寒、热证两大类。本研究旨在建立寒、热证之间的血浆代谢图谱, 并找出区分二者的潜在生物标志物。采用超高效液相色谱联合线性离子阱四极轨道质谱技术检测 296 例患者和 55 例健康儿童血浆样品, 其中 213 例为筛选组(热证 = 160 例, 寒证 = 23 例, 健康对照 = 30 例), 138 例为验证组(热证 = 93 例, 寒证 = 20 例, 健康对照 = 25 例)。寒、热证之间的差异性代谢物筛选方法为正交偏最小二乘判别分析 (OPLS-DA)、差异倍数、Kruskal-Wallis检验结合 FDR 错误发现率校准 (q值 < 0.05)。ROC曲线下面积 (AUC) 评价潜在生物标志物的诊断准确性。与健康对照组相比, 寒证中天冬氨酸、苯丙氨酸、精氨酸、溶血性磷脂酰胆碱 20:1、溶血性磷脂酰乙醇胺 16:0、溶血性磷脂酰乙醇胺 18:0 和磷脂酰乙醇胺 (16:0_22:6)表达水平升高, 而热证中磷脂酰胆碱 (18:1_18:1)、磷脂酰胆碱 (20:4_20:4)、磷脂酰乙醇胺 (16:0_18:2)、溶血性磷脂酰乙醇胺 20:4、溶血性磷脂酰乙醇胺 18:2 和溶血性磷脂酰乙醇胺 22:6表达水平降低。神经酰胺 (d18:1_24:1)是热证中唯一上调的物质。13 个差异性代谢物组合, 其区分寒证与健康对照的 AUC 为 0.995, 15 个差异性代谢物组合, 其区分热证与健康对照之间的 AUC 为 0.954。7个脂质组成的代谢物群组, 包括溶血性磷脂酰胆碱 20:1, 溶血性磷脂酰乙醇胺 16:0, 溶血性磷脂酰乙醇胺 18:2, 溶血性磷脂酰乙醇胺 20:4, 溶血性磷脂酰乙醇胺 22:6, 磷脂酰胆碱 (18:1_18:1), 磷脂酰胆碱 (20:4_20:4), 其区分寒证与热证的 AUC 为 0.982, 呈现出极好的诊断价值, 可作为区分儿童社区获得性肺炎寒、热证的潜在生物标志物。综上所述, 血浆中代谢紊乱的氨基酸和脂质为中医儿科辨证客观化提供了一定的依据。.
Keywords: cold syndrome; community-acquired pneumonia; heat syndrome; metabolomics; pediatrics of traditional Chinese medicine; 中医儿科; 代谢组学; 寒证; 热证; 社区获得性肺炎.
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