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Using latent class analysis (LCA) of clinical and protein biomarkers, researchers have identified two phenotypes of the acute respiratory distress syndrome (ARDS) with divergent clinical trajectories and treatment responses. We investigated whether plasma metabolites differed among patients with LCA-derived hyperinflammatory and hypoinflammatory ARDS, and we tested the prognostic utility of adding metabolic clusters to LCA phenotypes. We analyzed data from 93 patients with ARDS and sepsis enrolled in a multicenter prospective cohort of critically ill patients, comparing 970 metabolites between the two LCA-derived phenotypes. In all, 188 metabolites were differentially abundant between the two LCA-derived phenotypes. After adjusting for age, sex, confounding medications, and comorbid liver and kidney disease, 82 metabolites remained significantly different. Patients with hyperinflammatory ARDS had reduced circulating lipids but high levels of pyruvate, lactate, and malate. Metabolic cluster and LCA-derived phenotypes were each significantly and independently associated with survival. Patients with hyperinflammatory ARDS may be experiencing a glycolytic shift leading to dysregulated lipid metabolism. Metabolic profiling offers prognostic information beyond what is captured by LCA phenotypes alone. Deeper biological profiling may identify key differences in pathogenesis among patients with ARDS and may lead to novel targeted therapies. [ABSTRACT FROM AUTHOR]

A better understanding of the pathogenesis and the resolution of the acute respiratory distress syndrome (ARDS) is needed. Although some progress has been made with the use of protein biomarkers and candidate gene studies in understanding the pathobiology of ARDS, we propose that new studies that measure the chemical breakdown products of cellular metabolism (metabolomics) may provide new insights into ARDS, in part because metabolomics targets a later point in the genomics cascade than is possible with studies of DNA, RNA, and protein biomarkers. Technological advances have made largescale metabolomic profiling increasingly feasible. Metabolomic approaches have already achieved novel insights in nonpulmonary diseases such as diabetes mellitus and malignancy, as well as in sepsis, a major risk factor for developing ARDS. Metabolomic profiling is a promising approach to identify novel pathways in both patients at risk for developing ARDS as well as in the early phase of established ARDS. [ABSTRACT FROM AUTHOR]