Early differential protein expression in blood and bronchoalveolar fluid among ARDS phenotypes
Protein pathways underlying ARDS phenotypes are not fully elucidated. The aim of this subanalysis of an international randomized controlled clinical trial, which assessed the potential benefit of a maximal lung recruitment strategy, was to identify protein signatures in serum and bronchoalveolar fluid associated with ARDS phenotypes and to improve understanding of the underlying biological pathways. Whole proteomic profiling of serum and bronchoalveolar fluid was performed in 50 and 21 ARDS patients, respectively, and compared with 24 non-ARDS controls. ARDS patients were classified as hyperinflammatory (Hyper; n = 17) or hypoinflammatory (Hypo; n = 33) according to a previously validated three-variable classifier model. Sampling for proteomic analysis was performed at study inclusion, before any study intervention. Protein signatures differentiating hyper- and hypoinflammatory ARDS from controls consisted of 19 proteins in serum and 17 proteins in bronchoalveolar fluid. Proteins that are part of the acute phase response signaling pathway and the complement cascade were more highly expressed in Hypo than in Hyper. Canonical pathway analysis showed that inflammatory pathways, including the complement cascade, acute phase response, and cachexia signaling, were activated to a greater extent in Hypo than in Hyper. For some key molecules, canonical pathways and upstream regulators demonstrated different directions of activation between serum and bronchoalveolar fluid. Distinct ARDS phenotypes are associated with different early proteomic patterns in both serum and bronchoalveolar fluid. Inflammatory pathways and upstream regulators were more pronounced in the hypoinflammatory ARDS phenotype. Trial registration: ClinicalTrials.gov, NCT01667146
Authors
- Jacky Y. Suen (ORCID: https://orcid.org/0000-0002-0309-2524)
- E Paul
- Nicholas Matigian (ORCID: https://orcid.org/0000-0001-7735-9415)
- Shirley Vallance (ORCID: https://orcid.org/0000-0001-8567-1783)
- Meredith Young
- Nusha Chegeni
- Ciara Fahey
- Alex D. Colella (ORCID: https://orcid.org/0000-0002-4111-208X)
- Caroline E. Gebhard
- Gianluigi LiBassi
- Rachael L. Parke (ORCID: https://orcid.org/0000-0003-4209-0334)
- Shailesh Bihari (ORCID: https://orcid.org/0000-0001-7553-8620)
- Shay McGuinness (ORCID: https://orcid.org/0000-0003-0620-4787)
- Andrew John Davies (ORCID: https://orcid.org/0000-0002-7517-6938)
- Dani‐Louise Dixon (ORCID: https://orcid.org/0000-0001-6459-1856)
- Andrew Bersten
- Yaseen Arabi
- John Fraser
- Timothy Chataway
- Alistair Nichol
- Mahe Bouquet
- Lynne Murray
- Kathy Brickell
- Karin Wildi
- David Tuxen
- PHARLAP Study Investigators
- Margaret Passmore
- D. James Cooper
- Carol Hodgson
- Victoria King
- Alex Ritchie
Institutions
- University College Dublin (IE)
- The University of Queensland (AU)
- Flinders University (AU)
- King Saud bin Abdulaziz University for Health Sciences (SA)
- Triemli Hospital (CH)
- Auckland City Hospital (NZ)
- Frankston Hospital (AU)
- The Alfred Hospital (AU)
- Flinders Medical Centre (AU)
- Australian and New Zealand Intensive Care Society (AU)
- King Abdullah International Medical Research Center (SA)
- Digital Science (United States) (US)
- St. Vincent's University Hospital (IE)
- Prince Charles Hospital (AU)
- Medical Research Institute of New Zealand (NZ)
- Kantonsspital Aarau (CH)
- Monash University (AU)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-04-22
- DOI
- https://doi.org/10.1038/s41598-026-43956-0
- Primary Topic
- Respiratory Support and Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Flinders Medical Centre Foundation
- Universität Basel
- Australian and New Zealand College of Anaesthetists
- Flinders University
- University of Queensland
- Medical Research Council
- National Health and Medical Research Council
- Health Research Council of New Zealand