title: Proteomic profiles in acute respiratory distress syndrome differentiates survivors from non-survivors.
abstract: Acute Respiratory Distress Syndrome (ARDS) continues to have a high mortality. Currently, there are no biomarkers that provide reliable prognostic information to guide clinical management or stratify risk among clinical trial participants. The objective of this study was to probe the bronchoalveolar lavage fluid (BALF) proteome to identify proteins that differentiate survivors from non-survivors of ARDS. Patients were divided into early-phase (1 to 7 days) and late-phase (8 to 35 days) groups based on time after initiation of mechanical ventilation for ARDS (Day 1). Isobaric tags for absolute and relative quantitation (iTRAQ) with LC MS/MS was performed on pooled BALF enriched for medium and low abundance proteins from early-phase survivors (n = 7), early-phase non-survivors (n = 8), and late-phase survivors (n = 7). Of the 724 proteins identified at a global false discovery rate of 1%, quantitative information was available for 499. In early-phase ARDS, proteins more abundant in survivors mapped to ontologies indicating a coordinated compensatory response to injury and stress. These included coagulation and fibrinolysis; immune system activation; and cation and iron homeostasis. Proteins more abundant in early-phase non-survivors participate in carbohydrate catabolism and collagen synthesis, with no activation of compensatory responses. The compensatory immune activation and ion homeostatic response seen in early-phase survivors transitioned to cell migration and actin filament based processes in late-phase survivors, revealing dynamic changes in the BALF proteome as the lung heals. Early phase proteins differentiating survivors from non-survivors are candidate biomarkers for predicting survival in ARDS.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Maneesh
authors.initials: M
authors.lastname: Bhargava
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Trisha L
authors.initials: TL
authors.lastname: Becker
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Viken
authors.affiliation: Minnesota Supercomputer Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Pratik D
authors.initials: PD
authors.lastname: Jagtap
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Dey
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Steinbach
authors.affiliation: School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Baolin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Vipin
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Bitterman
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Ingbar
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America; Minneapolis VA Medical Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Wendt
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D011237:Predictive Value of Tests; D011379:Prognosis; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D016019:Survival Analysis; D017741:Survivors; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D015415:Biomarkers; D020543:Proteome