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