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Abstract
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 amongst patients with LCA-derived hyperinflammatory and hypoinflammatory ARDS, and tested the prognostic utility of adding metabolic clusters to LCA phenotypes. We analyzed data from 93 ARDS patients with sepsis enrolled in a multi-center prospective cohort of critically ill patients, comparing 970 metabolites between the two LCA-derived phenotypes. 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. Hyperinflammatory ARDS patients 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. Hyperinflammatory ARDS patients 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 biologic profiling may identify key differences in pathogenesis among patients with ARDS and lead to novel targeted therapies.
View details for DOI 10.1152/ajplung.00278.2022
View details for PubMedID 36648136