Bronchoalveolar Lavage Fluid Protein Expression in Acute Respiratory Distress Syndrome Provides Insights into Pathways Activated in Subjects with Different Outcomes

Sci Rep. 2017 Aug 7;7(1):7464. doi: 10.1038/s41598-017-07791-8.

Abstract

Acute respiratory distress syndrome (ARDS) is associated with high mortality. We sought to identify biological pathways in ARDS that differentiate survivors from non-survivors. We studied bronchoalveolar lavage fluid (BALF) from 36 patients with ARDS (20 survivors, 16 non-survivors). Each sample, obtained within seven days of ARDS onset, was depleted of high abundance proteins and labeled for iTRAQ LC-MS/MS separately. Protein identification and relative quantification was performed employing a target-decoy strategy. A variance weighted t-test was used to identify differential expression. Ingenuity Pathway Analysis was used to determine the canonical pathways that differentiated survivors from non-survivors. We identified 1115 high confidence proteins in the BALF out of which 142 were differentially expressed between survivors and non-survivors. These proteins mapped to multiple pathways distinguishing survivors from non-survivors, including several implicated in lung injury and repair such as coagulation/thrombosis, acute phase response signaling and complement activation. We also identified proteins assigned to fibrosis and ones involved in detoxification of lipid peroxide-mediated oxidative stress to be different in survivors and non-survivors. These results support our previous findings demonstrating early differences in the BALF protein expression in ARDS survivors vs. non-survivors, including proteins that counter oxidative stress and canonical pathways associated with fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Chromatography, Liquid
  • Female
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Humans
  • Male
  • Middle Aged
  • Mortality
  • Prognosis
  • Proteomics / methods*
  • Respiratory Distress Syndrome, Adult / metabolism*
  • Respiratory Distress Syndrome, Adult / mortality*
  • Signal Transduction
  • Tandem Mass Spectrometry