Lipid Profile and Differential Lipids in Serum Predict Severity of Community-Acquired Pneumonia: A Prospective, Multi-Centre Study

Background: This study aimed to characterize the lipidomic responses to community-acquired pneumonia (CAP), and validate the effectiveness of these lipids as indicators of the severity of the CAP as well as of the risk of death in severe CAP.Methods: Lipidomic profiles of serum were generated using ultra high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS). Principal component analysis (PCA) and supervised orthogonal partial least squares discriminant analysis (OPLS-DA) was implemented to distinguish between the classes of samples and to identify the differentially expressed variables. The area under the receiver operating characteristic curve of the significant differential lipids was compared. Spearman’s rank correlation test and multiple linear regression (MLR) analysis were applied to further explore the putative differentially expressed lipids correlation with clinical parameters. Kaplan–Meier methods were used to build 30-day survival curves, and survival rates were compared using the log-rank test.Results: A total of 6 categories and 509 lipid species were detected in the positive ion mode using UPLC-MS/MS. In the negative ion mode, 3 categories and 195 lipid species were detected. According to the screening criteria, 5 lipids in total were selected as target lipids, which are PC (16:0_18:1), PC (18:2_20:4), PC (20:5_18:2), PC (36:4) and PC (38:6). Area under curves (AUC) for all five li p ids were superior to PSI (0.749, 0.550-0.892) and CURB-65 (0.772, 0.575-0.908). PC (18: 2_20: 4), PC (38: 6) and PC (36: 4) was negatively related to FiO 2 and PC (18: 2_20: 4) was inversely correlated with the PCT. As the relative abundance of PC (16:0_18:1), PC (36: 4), PC (20: 5_18: 2) and PC (38: 6) decreased, the length of hospital stay significantly extended. There was a statistically significant difference in the probability of 30-day mortality between the high-abundance and low-abundance groups of PC (16: 0_18: 1), PC (36: 4) and PC (20: 5_18: 2) (og-rank p <0.05).Conclusion: Our research suggests that the serum lipidomics approach of the UHPLC-MS/MS platform can be used to reveal lipid changes during CAP and establish lipid profiles related to disease severity.Trial registration: ClinicalTrials.gov, NCT03093220. Registered on 28 March 2017 (retrospectively registered).