U01HL168145

Colorado APS Clinical Center - Colorado has a long and storied history of heterogeneity-related Acute Respiratory Distress Syndrome (ARDS), pneumonia, and sepsis (APS) research. After the initial Lancet description of 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 the 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 in academic rural recruiting historically underrepresented communities (Latinx, Black, and Indigenous) from both academic 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.

The Regents Of The Univ. Of Colorado

THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Aurora, Colorado 800452560 United States

Single Zip Code

ARDS, Pneumonia, and Sepsis Phenotyping Consortium Clinical Centers (U01 Clinical Trial Not Allowed) (RFA-HL-23-001)

Amendment Since initial award the total obligations have increased 2264% from $48,422 to $1,144,687.