title: Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset.
abstract: There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This "high metabolite" endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS.
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, Stanford, California; ajrogers@stanford.edu.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Rogers
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California.
authors.forename: Kévin
authors.initials: K
authors.lastname: Contrepois
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, California.
authors.forename: Manhong
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, California.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, California.
authors.forename: Gary
authors.initials: G
authors.lastname: Peltz
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine and Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.affiliation: Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, California.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D000328:Adult; D001826:Body Fluids / Q000378:metabolism*; D016000:Cluster Analysis; D003710:Demography; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D025341:Principal Component Analysis; D011654:Pulmonary Edema / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D015854:Up-Regulation
keywords: ARDS; endotype; metabolomics; phenotype; pulmonary edema