Vanderbilt University Medical Center has received a six-year, $31.6 million federal grant to lead a national effort to better understand acute respiratory distress syndrome (ARDS), pneumonia and sepsis, which together kill hundreds of thousands of people in the United States each year.
Grant HL168478 is jointly funded by the National Heart, Lung and Blood Institute, and the National Institute of General Medical Sciences of the National Institutes of Health (NIH).
The grant will support the Vanderbilt Coordinating Center for the NHLBI/NIGMS ARDS, Pneumonia and Sepsis (APS) Phenotyping Consortium. The center will operate out of the Vanderbilt Institute for Clinical and Translational Research (VICTR).
There are many different causes for and severities of ARDS, pneumonia, and sepsis. Treatment has been hampered by an incomplete understanding of how each syndrome develops. Now, emerging evidence suggests that ARDS, pneumonia and sepsis likely represent many distinct disorders with different underlying causes and disease mechanisms.
A major goal of the consortium is to understand the different types of ARDS, pneumonia, and sepsis, and from that, to develop treatments targeting specific dysfunctional pathways. Early work will focus on “phenotyping” ARDS, pneumonia and sepsis — identifying subtypes of each syndrome based on biological similarities and differences among different patients.
“The goal is to better understand the association of patient characteristics, especially their biochemistry and underlying pathophysiology, with outcomes,” said Gordon Bernard, MD, VUMC Executive Vice President for Research, VICTR program director and a principal investigator of the consortium’s coordinating center.
“Identifying and leveraging precision diagnoses will transform the methods of critical care research and medical practice, and ultimately will change the trajectory of patient outcomes for the better,” Bernard said.
“I think this is a tremendous opportunity to deepen our understanding of ARDS, pneumonia and sepsis,” added co-principal investigator Wesley Self, MD, VUMC Senior Vice President for Clinical Research, who will assume the role of VICTR director in July.
“Clinical trials for these illnesses during the past two decades have largely failed to identify new effective therapies,” Self said. “We are very hopeful that intense study of the mechanisms of disease over the next several years will lead to breakthroughs that will facilitate better treatments for these serious diseases.”
Under VUMC’s leadership, the APS Phenotyping Consortium will bring together many of the nation’s experts in phenotyping critical care illnesses. Through a network of 22 participating hospitals, the consortium will enroll at least 5,000 patients and perform extensive diagnostic testing, including laboratory testing of blood and respiratory specimens and imaging studies.
The six lead (hub) sites of the consortium, which is structured in a hub-and-spoke model, are VUMC, Intermountain Medical Center in Murray, Utah, University of California San Francisco, University of Michigan, University of Pennsylvania and University of Colorado.
The VUMC site is led by Lorraine Ware, MD, professor of Medicine, and Julie Bastarache, MD, associate professor of Medicine.
Bernard, the Melinda Owen Bass Professor of Medicine, was deeply engaged in initial efforts to standardize the definitions of ARDS and sepsis more than 30 years ago. Since then, VUMC has been at the forefront of efforts to understand these conditions through applications that include genetics, microbiology, biomarkers, clinical and laboratory data.
Self is a physician scientist who is nationally known for designing and conducting clinical research and for advancing the treatment of patients with severe infections.
Other key VUMC investigators in the consortium include:
- Frank Harrell, Jr., PhD, professor of Biostatistics, Matthew Shotwell, PhD, associate profess of Biostatistics, and Yaomin Xu, PhD, assistant professor of Biostatistics, who will lead the Design, Data, & Statistical Analysis Unit.
- James Chappell, MD, PhD, research professor of Pediatric Infectious Diseases, who will lead the biospecimen repository.
- Paul Harris, PhD, professor of Biomedical Informatics, and Alex Cheng, PhD, research assistant professor of Biomedical Informatics, who will lead the bioinformatics work.
- Todd Rice, MD, MSc, associate professor of Medicine, who will lead the Clinical Research Management unit.
- Jillian Rhoads, PhD, VICTR senior scientific project manager, who will serve as the program’s organizational lead.
- Chris Lindsell, PhD, data coordinating center investigator.
- VICTR Executive Director Jill Pulley, MBA, and Jana Shirey-Rice, PhD, translational science team lead.
This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.