Project Summary This proposal presents the Intermountain West-Atlantic Center (InterACT), which brings together four robust investigative sites to participate in the APS Phenotypes Consortium. InterACT proposes to use robust statistical and machine learning methods to phenotype patients with Acute Respiratory Distress Syndrome (ARDS), pneumonia, and sepsis in two broad proposals. In the first proposal for the entire Consortium, we will use multiplex cytokine arrays and clinical variables in the setting of normalized treatment trajectories to improve the accuracy of phenotyping by accounting for the role treatment plays. This method creates phenotypes that will be confirmed, with an eye toward therapeutic implications, in emulated clinical trials. In the second proposal for the Center specifically, we will focus our statistical methodology on new work investigating the pattern of tissue injury and repair, with a focus on hyaluronan and soluble Receptor for Advanced Glycation Endproducts (sRAGE) as tissue injury biomarkers and predictors of dysregulated inflammation. This work will culminate in emulated trials of novel agents that modulate the pathologic consequences of tissue injury. Together these highly innovative proposals promise actionable, treatment-responsive patient phenotypes for future clinical trials.

Project Narrative The Intermountain West-Atlantic Center (InterACT) brings together four technically experienced, high-enrolling sites to participate in the APS Phenotypes Consortium. InterACT will use robust statistical methods to phenotype patients with Acute Respiratory Distress Syndrome (ARDS), pneumonia, and sepsis in two broad proposals that incorporate target trial emulation to confirm phenotypes. The Consortium-wide proposal focuses on clinical data and inflammatory cytokines, while the Center-specific proposal investigates hyaluronan and tissue injury and repair pathways.