A Genome-Wide Expression Analysis in Blood Identifies Pre-Elafin as a Biomarker in ARDS

Details

• Personal Author:
  Beach D ; Cristiani DC ; Su L ; Wang Z ; Zhai R
• Description:
  Previous microarray-based studies of acute respiratory distress syndrome (ARDS) were performed using various models to mimic disease pathogenesis. The complexity of the pathophysiologic response to direct or indirect lung injury in ARDS is difficult to reconstruct in experimental conditions. Thus, direct analysis of ARDS patient blood may provide valuable information. We investigated genome-wide gene expression profiles in paired whole blood samples from patients with ARDS (n = 8) during the acute stage (within 3 d of diagnosis) and recovery stage of ARDS (around ICU discharge). Among 126 differentially expressed genes, peptidase inhibitor 3 (PI3, encoding elafin, a potent neutrophil elastase inhibitor) had the largest fold-change (-3-fold changes, acute stage/recovery stage) in expression, indicating down-regulation during the acute stage of ARDS. We further examined plasma PI3 levels in 40 patients with ARDS and 23 at-risk control subjects from the same cohort. There was a coincidence of the microarray findings of lower PI3 gene expression with the lower plasma PI3 during the acute-stage. The plasma PI3 levels were statistically significant different among pre-diagnosis, day of diagnosis, and post-diagnosis groups (ANOVA, P = 0.001), with a trend of decreasing from pre- to post-diagnosis group. The time course of plasma PI3 decrease is well correlated with the course of early ARDS development (Pearson correlation coefficient: -0.52, P = 0.0006). Considering that PI3 can covalently binding to extracellular matrix in lung, circulating PI3 may provide a useful clinical marker for monitoring the early development of ARDS and may have implications for ARDS treatment. [Description provided by NIOSH]
• Subjects:
  Age Factors Aging Biomarkers Blood Lung Lung Diseases Men Occupational Health Pathology Respiratory System Respiratory Tract Diseases Safety Women

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• Keywords:
  Acute Respiratory Distress Syndrome Age Factors Age Groups Author Keywords: Gene Expression Profiling Diseases Elafin Genetic Disorders Genomics Humans Injuries Lung Disease Pathogenesis Physiological Response Physiopathology Pulmonary System Disorders Respiratory Function Respiratory System Disorders Sampling Transcriptomics

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• ISSN:
  1044-1549
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  38
• Issue:
  6
• NIOSHTIC Number:
  nn:20059694
• Citation:
  Am J Respir Cell Mol Biol 2008 Jun; 38(6):724-732
• Contact Point Address:
  Zhaoxi Wang, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115
• Email:
  mikewang@hsph.harvard.edu
• Federal Fiscal Year:
  2008
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  American Journal of Respiratory Cell and Molecular Biology
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:70acc6000de0cb8343862547467c14b155182e3bf59248afc6de23c4862624b2894fd137882f76e82f607b9811dc967e87684c0410cedb05e5a5ca6496d0b531
• Download URL:
  https://stacks.cdc.gov/view/cdc/223831/cdc_223831_DS1.pdf
• File Type:
  [PDF - 323.17 KB ]