Metabolomic Analysis in Sepsis Induced Acute Respiratory Distress Syndrome 公开
Martin, Ralitza (2014)
Published
Abstract
Abstract
Metabolomic Analysis in Sepsis Induced Acute Respiratory
Distress Syndrome By Ralitza Martin
Rationale: Metabolomic analysis is a novel approach in
critical illness providing rapid analysis of metabolites from
various biological materials, such as plasma and bronchoalveolar
lavage fluid (BALF), with minimal sample preparation. This study
tested if metabolomics could discriminate sepsis patients according
to development of ARDS and mortality.
Methods: Prospective cohort of adult ICU patients at Grady Memorial
Hospital meeting the ACCP/SCCM definition of severe sepsis or
septic shock. Following informed consent, each subject underwent
blood sampling and bronchoscopy with BAL. BALF and plasma were
analyzed on a LCMS metabolomics platform using C18 chromatography
and high-resolution mass spectrometry and analyzed using LIMMA to
identify differentially expressed metabolites (DEMs) after
adjusting for false discovery rate (FDR). Classification accuracies
were evaluated using 10-fold cross-validation (CV) using support
vector machine.
Results: Metabolomic analysis was performed on 79 BALF and
plasma samples, 42 had ARDS. The mean age of the cohort was 53.9
years, 59 % male, 68% black. The overall mortality for the cohort
was 48%. There was no mortality difference between ARDS and
non-ARDS patients (42.9% vs. 54.1%, p=0.32). BALF FDR analysis
between survivors and non-survivors of sepsis revealed 37 DEMs with
85.9% 10-fold CV classification accuracy. Top 500 metabolites from
the network analysis were found to be significantly enriched in the
lipid and drug metabolism, and aminoacid biosynthesis pathways.
BALF analysis between ARDS and non-ARDS patients showed 35 DEMs
with 92.1% CV accuracy, with pathways for aminoacid and drug
metabolism, significantly enriched. Analysis of plasma did not
reveal any significant DEMs in regards to development of ARDS or
mortality after FDR correction.
Conclusion: While BALF metabolites were able to discriminate
between sepsis non-survivors and survivors, and those developing
ARDS or not, plasma metabolites could not. Sampling of the lung
compartment may be necessary to understand the metabolic changes
occurring in ARDS that may be linked to survival.
Table of Contents
TABLE OF CONTENTS
Introduction 1-2
Background 3-11
Methods 12-16
Results 17-20
Discussion 21-24
Table 1 25
Table 2 26
Table 3a 27
Table 3b 28
Figure 1 29
Figure 2 30
Table 4 31
Figure 3 32
Figure 4 33
Table 5 34
References 35-37
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