title: Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.
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.
authors: Department of Medicine, Division of Hospital Medicine, University of California-San Francisco, San Francisco, California; kirsten.kangelaris@ucsf.edu.
authors: Kirsten Neudoerffer
authors: KN
authors: Kangelaris
authors: Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California;
authors: Arun
authors: A
authors: Prakash
authors: Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California; Cardiovascular Research Institute, University of California-San Francisco, San Francisco, California;
authors: Kathleen D
authors: KD
authors: Liu
authors: Department of Physiologic Nursing, University of California-San Francisco, San Francisco, California; Institute for Human Genetics, University of California-San Francisco, San Francisco, California;
authors: Bradley
authors: B
authors: Aouizerat
authors: 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.
authors: Prescott G
authors: PG
authors: Woodruff
authors: Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California-San Francisco, San Francisco, California; and.
authors: David J
authors: DJ
authors: Erle
authors: 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.
authors: Angela
authors: A
authors: Rogers
authors: Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California-San Francisco, San Francisco, California; and.
authors: Eric J
authors: EJ
authors: Seeley
authors: Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California;
authors: Jeffrey
authors: J
authors: Chu
authors: Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California;
authors: Tom
authors: T
authors: Liu
authors: Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California;
authors: Thomas
authors: T
authors: Osterberg-Deiss
authors: Departments of Medicine and Anesthesia, University of California-San Francisco, San Francisco, California;
authors: Hanjing
authors: H
authors: Zhuo
authors: 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.
authors: Michael A
authors: MA
authors: Matthay
authors: 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.
authors: Carolyn S
authors: CS
authors: Calfee
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D009504:Neutrophils / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000209:etiology / Q000235:genetics / Q000276:immunology; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000276:immunology; D059467:Transcriptome
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger
keywords: ARDS; gene expression; neutrophils; sepsis