Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity

Abstract

BackgroundThis study aimed to determine whether community-acquired pneumonia (CAP) had a metabolic profile and whether this profile can be used for disease severity assessment.MethodsA total of 175 individuals including 119 CAP patients and 56 controls were enrolled and divided into two cohorts. Serum samples from a discovery cohort (n = 102, including 38 non-severe CAP, 30 severe CAP, and 34 age and sex-matched controls) were determined by untargeted ultra-high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomics. Selected differential metabolites between CAP patients versus controls, and between the severe CAP group versus non-severe CAP group, were confirmed by targeted mass spectrometry assays in a validation cohort (n = 73, including 32 non-severe CAP, 19 severe CAP and 22 controls). Pearson’s correlation analysis was performed to assess relationships between the identified metabolites and clinical severity of CAP. The area under the curve (AUC), sensitivity and specificity of the metabolites for predicting the severity of CAP were also investigated.ResultsThe metabolic signature was markedly different between CAP patients and controls. Fifteen metabolites were found to be significantly dysregulated in CAP patients, which were mainly mapped to the metabolic pathways of sphingolipid, arginine, pyruvate and inositol phosphate. The alternation trends of five metabolites among the three groups including sphinganine, p-Cresol sulfate, dehydroepiandrosterone sulfate (DHEA-S), lactate and l-arginine in the validation cohort were consistent with those in the discovery cohort. Significantly lower concentrations of sphinganine, p-Cresol sulfate and DHEA-S were observed in CAP patients than in controls (p < 0.05). Serum lactate and sphinganine levels were positively correlated with confusion, urea level, respiratory rate, blood pressure, and age > 65 years (CURB-65), pneumonia severity index (PSI) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, while DHEA-S inversely correlated with the three scoring systems. Combining lactate, sphinganine and DHEA-S as a metabolite panel for discriminating severe CAP from non-severe CAP exhibited a better AUC of 0.911 (95% confidence interval 0.825–0.998) than CURB-65, PSI and APACHE II scores.ConclusionsThis study demonstrates that serum metabolomics approaches based on the LC-MS/MS platform can be applied as a tool to reveal metabolic changes during CAP and establish a metabolite signature related to disease severity.Trial registrationClinicalTrials.gov, NCT03093220. Registered retrospectively on 28 March 2017.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2049-2) contains supplementary material, which is available to authorized users.

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

“…Sphingolipids are an important part of the structure of biological membranes and has complex biological functions, such as mediating inflammation [28], regulating proliferation, signal transduction, and migration of cells, as well as apoptosis [29][30]. Previous studies have shown significant changes in sphingolipid metabolism pathways in BALF [9] and serum [31] in CAP patients. Imbalances in the sphingolipid metabolism pathways also occur in other lung inflammatory diseases, such as asthma [32] and chronic obstructive pulmonary disease [33].…”

Molecular Diagnostics in Pulmonary Infections

“…A separate group used 1D 1H nuclear magnetic resonance (NMR) spectra to generate metabolic profiles from 15 patients with pneumonia; comparing the metabolic profiles using Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) they were able to differentiate cases of VAP from those without [104]. Finally, Ning et al analyzed 119 patients with CAP and found markedly different metabolic patterns as assessed by liquid chromatographymass spectrometry (LC-MS) compared with control patients [105]. Sphinganine, p-Cresol sulfate, and DHEA-S were significantly lower, and in combination with lactate, this panel could dis-criminate severe CAP from non-severe CAP with an impressive AUC of 0.911, better than the CURB-65, PSI, and APACHE II scores [105].…”

“…Finally, Ning et al analyzed 119 patients with CAP and found markedly different metabolic patterns as assessed by liquid chromatographymass spectrometry (LC-MS) compared with control patients [105]. Sphinganine, p-Cresol sulfate, and DHEA-S were significantly lower, and in combination with lactate, this panel could dis-criminate severe CAP from non-severe CAP with an impressive AUC of 0.911, better than the CURB-65, PSI, and APACHE II scores [105].…”

Discovery and Predictive Modeling of Urine Microbiome, Metabolite and Cytokine Biomarkers in Hospitalized Patients with Community Acquired Pneumonia

“…nutrition and drug treatment) and internal microbiome influences. Metabolites are dynamic analytes present in biological fluids, including urine, producing unique signatures that are readily detected with mass spectrometry and are currently being studied in patients with pneumonia [17][18][19][20] . While these studies have made great strides in elucidating underlying mechanisms of pneumonia and determined some promising biomarkers for specific causative agents, none have combined metabolomics and microbial-omics nor expanded from the discovery phase to algorithmic predictive modeling.…”