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

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.

• Authors: 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
• Journal: Intensive care medicine (Intensive Care Med) Vol. 39 Issue 8 Pg. 1423-34 (Aug 2013) ISSN: 1432-1238 [Electronic] United States
• PMID: 23673400 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Aged
• Aged, 80 and over
• Case-Control Studies
• Cohort Studies
• Community-Acquired Infections (blood, genetics, metabolism)
• Female
• Humans
• Male
• Metabolomics
• Pneumonia (blood, genetics, metabolism)
• Prospective Studies
• Sepsis (blood, genetics, metabolism)