Colorado APS Clinical Center

Colorado has a long and storied history of heterogeneity-related ARDS, pneumonia, and sepsis (APS) research. After the initial Lancet description of the acute respiratory distress syndrome (ARDS), Colorado investigators subsequently identified pneumonia and sepsis as diagnoses associated with an increased

susceptibility for ARDS. Since that time, Colorado investigators (including many key personnel on this proposal) have reported seminal discoveries regarding heterogeneity of ARDS, pneumonia, and sepsis including identification of a) alcohol use disorders (AUDs) as the first co-morbid conditions that increase

susceptibility to ARDS, b) AUDs deleterious impact on sepsis mortality, c) and sex, racial, and ethnic differences in ARDS and sepsis epidemiology. Simultaneously, Colorado investigators have been unraveling the basic mechanisms of APS focusing on heterogeneity in the host inflammatory response. As a higher

proportion of patients began to survive APS, we expanded our research to examine survivorship focusing on neuromuscular dysfunction. These studies have resulted in enhanced ways to diagnose weakness and improve our understanding of the neuromuscular trajectory of recovery in APS survivors. We propose to

conduct two clinical center-specific scientific projects demonstrating the breadth and depth of our research that spans acute APS severity and its recovery trajectory in survivors. The acute project will identify distinct mononuclear cell endotypes present in the lungs and blood of APS participants with acute respiratory failure

using bulk RNA seq. The recovery project will establish whether neuromuscular endotypes, based primarily on a single time-point nerve conduction study, can identify distinct and clinically relevant trajectories of recovery. We will also explore the cross-cutting theme of how AUDs impact APS heterogeneity. Building upon a strong

and persistent research foundation, we have the research infrastructure to achieve all the outlined goals and are poised to be a strong contributor to the national APS consortium. As an original and integral member of the ARDS and then PETAL Network (for over 28 consecutive years), our multi-disciplinary and collaborative

research group is experienced in conducting high quality NIH-funded prospective cohort research. In 2021, the Colorado research group enrolled 554 APS participants into clinical and translational research studies. This number far exceeds the APS consortium requirement of 240 APS patients per year. We also have extensive

expertise academic rural recruiting historically underrepresented communities (Latinx, Black, and Indigenous) from both and community hospitals. For this proposal, we will also enroll participants from the often overlooked community, ensuring their representation in the APS consortium.In summary, the Colorado APS Center

plans to exceed our enrollment obligations; maintain excellence in the quality of protocol compliance, data acquisition, and regulatory responsibilities; actively contribute to the steering committee and other APS committees; and most importantly advance science and contribute to improving the care of APS patients.