Resilience Endotype-derivation through Parsimonious Analysis and causal Inference of Recovery from Acute Respiratory Distress Syndrome (REPAIR-ARDS)

Project Summary Acute Respiratory Distress Syndrome (ARDS) is a serious lung injury requiring critical and complex care in the Intensive Care Unit (ICU). ARDS results in increased capillary permeability and fluid build-up in the lungs which affects oxygen delivery to red blood cells and leads to non-compliant or "stiff" lungs. Sepsis and trauma remain the major contributors to ARDS among patients admitted to the ICU. Each year, more than 200,000 Americans are diagnosed with ARDS and receive intensive care treatment, resulting in more than 3.6 million hospital days. Mortality rates are extremely high, with an average reported figure of 43% overall, representing a disease deadlier than ischemic heart disease and embolic stroke. There is still no pharmaceutical treatment available for ARDS; however, a number of interventions have been shown to be highly effective in reducing mortality. ARDS continues to be underdiagnosed and missed in up to half of the mild cases. This prevents the judicious and timely applications of effective interventions that have been proven to reduce mortality. Our project seeks to develop and validate predictive models of ARDS using protein biomarkers and clinical data for early diagnosis (Aim 1). Early detection of ARDS using parsimonious biomarkers is needed to improve recognition and timely administration of supporting interventions. We also seek to elucidate resiliency markers and endotypes associated with ARDS recovery using an integrated multiomics pipeline (Aim 2). Underlying biological mechanisms that drive severity and recovery are still unknown. There is now a distinct interest in identifying ‘host-factor resilience’, defined as ability of a host to tolerate the effects of an infection or other significant perturbation and promote salutogenesis. Our main goal is to characterize such protective factors among those who recovery to discover possible therapeutic targets of ARDS. This complex undertaking necessitates a holistic analysis supported by the integration of multiomics sources, such as transcriptomics, metabolomics, proteomics and lipidomics to gain crucial insights into the host-factors that drive resilience and recovery among the critically ill patients.