The acute respiratory distress syndrome (ARDS) remains a common and frequently fatal cause of acute respiratory failure in critically ill patients, with no specific preventative strategies or therapies available. The goal of this project is to study the clinical and biological features of ARDS subtypes in a broad sample of patients with ARDS and to determine how these subtypes change over time, in order to tailor therapy to individual ARDS patients and thereby improve clinical outcomes from ARDS.
This award will support investigation of the novel hypothesis that ARDS contains two distinct subphenotypes (also known as “endotypes”). Dr. Calfee recently identified and validated the presence of two distinct endotypes of ARDS in three large randomized controlled trials.16 These endotypes had strikingly different clinical characteristics, biomarker profiles, and clinical outcomes, and significant endotype-specific treatment responses were identified within a clinical trial previously thought to be “negative.” However, because these endotypes were identified in the setting of randomized controlled trials, using a narrow set of clinical and biological data, it remains unknown whether an expanded set of clinical characteristics and biomarkers would contribute significantly to ARDS endotype identification. Likewise, it remains unknown whether patients can transition between ARDS endotypes over the course of their illness and how the biology of each endotype evolves over the first several days of ARDS. The research proposed for this award will directly address these gaps in knowledge about ARDS endotypes, so as to improve our ability to design personalized therapies tailored to the biology of disease for critically ill patients with ARDS.