Newswise — ANN ARBOR, MI – Critical care takes a team—in research as well as in practice. For the first time ever, the University of Michigan, Henry Ford Hospital, the University of Cincinnati and the University of Chicago are teaming up to study and combat life-threatening critical illnesses. Funded by the National Institutes of Health (NIH) and led by members of the University of Michigan Max Harry Weil Institute for Critical Care Research and Innovation, the new collective named the Great Lakes Clinical Center (GLCC) for the ARDS, Pneumonia and Sepsis (APS) Phenotyping Consortium will be intensely focused on examining the various biologic mechanisms underpinning APS conditions to better understand their impact on disease development, trajectory and outcomes.
Dr. Robert Dickson, Deputy Director of the Weil Institute and Associate Professor of Pulmonary and Critical Care Medicine, is one of the principal investigators leading the GLCC’s University of Michigan site, together with Dr. Robert Hyzy and Dr. Hallie Prescott—both Weil Institute members and Professor and Associate Professor, respectively, of Pulmonary and Critical Care Medicine. Over the next six years, their group will use the $6 million NIH grant to collaborate with a nationwide observational study of 5,000 adult patients hospitalized with APS. The four sites within the GLCC will partner with five other clinical sites to use novel data collection approaches to target key research questions, such as how a patient’s body composition impacts survival and how the relationship between skin color and pulse oximetry affects APS outcomes.
ARDS, pneumonia and sepsis are life-threatening conditions that are also known to overlap: pneumonia is a common cause of sepsis, and both sepsis and pneumonia can contribute to ARDS. While progress has been made to reduce mortality across each, this overlap combined with the illnesses’ heterogeneity—the significant variations in their root causes—has constrained the development of new therapeutics.
“Imagine trying to cure a patient with a fever before knowing that fever can be caused by completely distinct disease processes: infection, cancer, or autoimmune disease,” said Dr. Dickson. “You’d be stuck working with symptomatic treatments like acetaminophen, with no hope of resolving the underlying problem. In a real way, that’s where we are with APS conditions: providing supportive care without a working knowledge of the underlying biology.”
This summer will mark the Great Lakes Clinical Center’s official start and will see the four sites meet with the nationwide network to harmonize the research and data collection protocols that will guide the consortium for the next six years.
“We are not only combining our clinical and scientific expertise with our GLCC partners; we are also combining our patient populations,” said Dr. Hyzy. “Our service area represents over 3 million people and includes major urban centers such as downtown Chicago, Detroit, and Cincinnati. We will be studying a patient cohort far more demographically diverse than what we would see at Michigan Medicine alone. I’m proud and excited that we’ll be studying these conditions in a such a diverse patient population.”
To better understand outcomes and recovery after APS, the consortium will also collect follow-up data from patients at three, six, and twelve months post-discharge.
“Many patients do not experience full recovery when they leave the ICU,” said Dr. Prescott. “They might plateau or decline in the year after discharge, and many get rehospitalized. This consortium will be an amazing opportunity to study the biological and clinical trajectories experienced by our patients after they leave the hospital.”
In tandem with the consortium-wide study, each GLCC site will conduct its own center-specific research. The University of Michigan team and its partners will study the microbiome—the bacterial communities that live in our digestive and respiratory tracts—to determine the role it plays in the development, trajectory, and recovery of APS conditions.
“The microbiome is an important yet poorly understood source of biologic heterogeneity, and it represents a highly promising treatment target,” said Dr. Dickson. “Our team will use cutting-edge molecular techniques to identify the pathways by which gut and respiratory microbiota participate in the acute development and trajectory of APS conditions. This will be an important step in the direction of developing microbiome-targeted therapies to prevent and treat these conditions.”
The GLCC is supported by a U01 “ARDS, Pneumonia, and Sepsis Phenotyping Consortium Clinical Centers” grant provided by the NIH Heart, Lung, and Blood Institute (NHLBI) and National Institute of General Medical Sciences (NIGMS). “We pulled in a lot of expertise to make this grant happen,” said Dr. Dickson. “Our strengths at Michigan Medicine are a big part of what made us so competitive. We have a rich tradition of clinical research in the intensive care unit as well as expertise in long-term outcomes and the microbiome. We also have the largest research institute in the country dedicated to the study of critical care. I can’t imagine a network like this not wanting to involve the Weil Institute.”
“We are thrilled to be partnering with Michigan Medicine and the Weil Institute on this project,” said Dr. Bhakti Patel, Assistant Professor of Medicine at the University of Chicago. “This will be an extraordinary opportunity to bridge our institutions’ strengths in clinical research and microbiome science, all in the interest of providing better care for our sickest patients.”
Ultimately, the GLCC and the nationwide network aims to make its collection of clinical and imaging data and biospecimens publicly available, providing investigators around the world with a wealth of opportunities for further study into clinical disease trajectories; blood cytokines, DNA, RNA, and metabolites; gastrointestinal and respiratory microbiota; and chest and body imaging. This, in turn, will help inform future clinical trials and further guide the development of new and improved therapeutics.
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