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Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity
- Source :
- Critical Care, Vol 22, Iss 1, Pp 1-14 (2018), Critical Care
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- Background This study aimed to determine whether community-acquired pneumonia (CAP) had a metabolic profile and whether this profile can be used for disease severity assessment. Methods A 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. Results The 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 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. Conclusions This 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 registration ClinicalTrials.gov, NCT03093220. Registered retrospectively on 28 March 2017. Electronic supplementary material The online version of this article (10.1186/s13054-018-2049-2) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
0301 basic medicine
Metabolite
Pneumonia severity index
Critical Care and Intensive Care Medicine
Liquid chromatography–mass spectrometry
Severity of Illness Index
Gastroenterology
Cohort Studies
Cresols
chemistry.chemical_compound
0302 clinical medicine
Community-acquired pneumonia
APACHE
APACHE II
Dehydroepiandrosterone Sulfate
Area under the curve
lcsh:Medical emergencies. Critical care. Intensive care. First aid
Middle Aged
Community-Acquired Infections
Cohort
Biomarker (medicine)
Female
China
medicine.medical_specialty
macromolecular substances
Sulfuric Acid Esters
Arginine
Severity
03 medical and health sciences
Dehydroepiandrosterone sulfate
Internal medicine
medicine
Humans
Metabolomics
Lactic Acid
Physical Examination
Retrospective Studies
Sphingolipids
business.industry
Research
030208 emergency & critical care medicine
Pneumonia
Biomarker
lcsh:RC86-88.9
medicine.disease
Metabolism
030104 developmental biology
chemistry
business
Biomarkers
Chromatography, Liquid
Subjects
Details
- Language :
- English
- ISSN :
- 13648535 and 03093220
- Volume :
- 22
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Critical Care
- Accession number :
- edsair.doi.dedup.....75ea821e85977cbc019ee6d9e9e38d04