Intensive Care Medicine

, Volume 39, Issue 8, pp 1423–1434

Metabolomics in pneumonia and sepsis: an analysis of the GenIMS cohort study

  • Christopher W. Seymour
  • Sachin Yende
  • Melanie J. Scott
  • John Pribis
  • Robert P. Mohney
  • Lauren N. Bell
  • Yi-Fan Chen
  • Brian S. Zuckerbraun
  • William L. Bigbee
  • Donald M. Yealy
  • Lisa Weissfeld
  • John A. Kellum
  • Derek C. Angus
Original

DOI: 10.1007/s00134-013-2935-7

Cite this article as:
Seymour, C.W., Yende, S., Scott, M.J. et al. Intensive Care Med (2013) 39: 1423. doi:10.1007/s00134-013-2935-7

Abstract

Purpose

To determine the global metabolomic profile as measured in circulating plasma from surviving and non-surviving patients with community-acquired pneumonia (CAP) and sepsis.

Methods

Random, outcome-stratified case–control sample from a prospective study of 1,895 patients hospitalized with CAP and sepsis. Cases (n = 15) were adults who died before 90 days, and controls (n = 15) were adults who survived, matched on demographics, infection type, and procalcitonin. We determined the global metabolomic profile in the first emergency department blood sample using non-targeted mass-spectrometry. We derived metabolite-based prognostic models for 90-day mortality. We determined if metabolites stimulated cytokine production by differentiated Thp1 monocytes in vitro, and validated metabolite profiles in mouse liver and kidney homogenates at 8 h in cecal ligation and puncture (CLP) sepsis.

Results

We identified 423 small molecules, of which the relative levels of 70 (17 %) were different between survivors and non-survivors (p ≤ 0.05). Broad differences were present in pathways of oxidative stress, bile acid metabolism, and stress response. Metabolite-based prognostic models for 90-day survival performed modestly (AUC = 0.67, 95 % CI 0.48, 0.81). Five nucleic acid metabolites were greater in non-survivors (p ≤ 0.05). Of these, pseudouridine increased monocyte expression of TNFα and IL1β versus control (p < 0.05). Pseudouridine was also increased in liver and kidney homogenates from CLP mice versus sham (p < 0.05 for both).

Conclusions

Although replication is required, we show the global metabolomic profile in plasma broadly differs between survivors and non-survivors of CAP and sepsis. Metabolite-based prognostic models had modest performance, though metabolites of oxidative stress may act as putative damage-associated molecular patterns.

Keywords

SepsisPneumoniaMetabolomicsBiomarker

Supplementary material

134_2013_2935_MOESM1_ESM.docx (26 kb)
Supplementary material 1 (DOCX 26 kb)
134_2013_2935_MOESM2_ESM.docx (404 kb)
Supplementary material 2 (DOCX 403 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2013

Authors and Affiliations

  • Christopher W. Seymour
    • 1
    • 2
  • Sachin Yende
    • 2
    • 3
  • Melanie J. Scott
    • 2
    • 4
  • John Pribis
    • 4
  • Robert P. Mohney
    • 5
  • Lauren N. Bell
    • 5
  • Yi-Fan Chen
    • 6
  • Brian S. Zuckerbraun
    • 4
  • William L. Bigbee
    • 7
  • Donald M. Yealy
    • 8
  • Lisa Weissfeld
    • 6
  • John A. Kellum
    • 2
    • 3
  • Derek C. Angus
    • 2
    • 3
  1. 1.Department of Critical Care Medicine and Emergency MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of Critical Care, Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) CenterUniversity of PittsburghPittsburghUSA
  3. 3.Department of Critical CareUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of SurgeryUniversity of Pittsburgh School of MedicinePittsburghUSA
  5. 5.Metabolon, Inc.DurhamUSA
  6. 6.Department of Biostatistics, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  7. 7.Magee Women’s Research InstituteUniversity of PittsburghPittsburghUSA
  8. 8.Department of Emergency MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA