TY - JOUR
T1 - Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS
AU - Kangelaris, Kirsten Neudoerffer
AU - Prakash, Arun
AU - Liu, Kathleen D.
AU - Aouizerat, Bradley
AU - Woodruff, Prescott G.
AU - Erle, David J.
AU - Rogers, Angela
AU - Seeley, Eric J.
AU - Chu, Jeffrey
AU - Liu, Tom
AU - Osterberg-Deiss, Thomas
AU - Zhuo, Hanjing
AU - Matthay, Michael A.
AU - Calfee, Carolyn S.
N1 - Publisher Copyright:
© 2015 the American Physiological Society.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS.
AB - The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS.
KW - ARDS
KW - Gene expression
KW - Neutrophils
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=84930842760&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930842760&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00380.2014
DO - 10.1152/ajplung.00380.2014
M3 - Article
C2 - 25795726
AN - SCOPUS:84930842760
SN - 1040-0605
VL - 308
SP - L1102-L1113
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 11
ER -