Format

Send to

Choose Destination
Am J Physiol Lung Cell Mol Physiol. 2015 Jun 1;308(11):L1102-13. doi: 10.1152/ajplung.00380.2014. Epub 2015 Mar 20.

Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.

Author information

1
Department of Medicine, Division of Hospital Medicine, University of California-San Francisco, San Francisco, California; kirsten.kangelaris@ucsf.edu.
2
Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California;
3
Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California; Cardiovascular Research Institute, University of California-San Francisco, San Francisco, California;
4
Department of Physiologic Nursing, University of California-San Francisco, San Francisco, California; Institute for Human Genetics, University of California-San Francisco, San Francisco, California;
5
Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California-San Francisco, San Francisco, California; and.
6
Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California-San Francisco, San Francisco, California; and.
7
Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California-San Francisco, San Francisco, California; and Department of Pulmonary and Critical Care, Stanford University, Stanford, California.
8
Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California; Cardiovascular Research Institute, University of California-San Francisco, San Francisco, California; Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California-San Francisco, San Francisco, California; and.

Abstract

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.

KEYWORDS:

ARDS; gene expression; neutrophils; sepsis

PMID:
25795726
PMCID:
PMC4451399
DOI:
10.1152/ajplung.00380.2014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center