Plasma characteristic metabolites of pediatric community-acquired pneumonia in traditional Chinese medicine syndrome differentiation.

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.