Understanding Neuroinflammation and Cardiorespiratory Patterning to Improve Patient Care

Innovations in Pulmonary & Sleep Medicine | Fall 2022

Brainstem inflammation as a result of injury, infection and inflammation in the periphery of the body alters respiratory patterns and heart rate variability in animal models. Gaining a clearer understanding of this relationship may allow clinicians to better care for critically ill patients, including those with COVID-19.

Frank Jacono, MD, Chief of the Division of Pulmonary, Critical Care and Sleep Medicine at University Hospitals Cleveland Medical Center, and the Virginia Hubbell Chair in Pulmonary and Critical Care Medicine, recently received funding from the National Institutes of Health (NIH) to study how neuroinflammation maladapts cardiorespiratory circuits and patterns. 

Frank Jacono, MD

“Inflammation changes the pattern of breathing generated by the brain,” says Dr. Jacono. “It alters neural control of both the breathing rate and breathing pattern. Our long-term goal is to develop non-invasive biomarkers we can apply to patients in the Intensive Care Unit, the Emergency Room and possibly even at home, to serve as early warning signs that patients are getting sicker because of developing peripheral injury or infection.”

Dr. Jacono says this research will also help clinicians risk stratify patients, so they know which patients with sepsis, for example, are getting better and which are not and need an escalation in their therapy.

“This can be hard to discriminate clinically,” he says. “It’s an opportunity to personalize medicine and treatments to more precisely care for these patients.”

Understanding Links Between Infection and Inflammation

This study hopes to answer the question of whether the type of injury or infection in peripheral organs influences neuroinflammation and changes the connectivity between collections of neurons in the brainstem. Dr. Jacono will use three prospective models – systemic endotoxemia, bacterial infections in the peritoneum and non-infectious injury to the lungs leading to Acute Respiratory Distress Syndrome – to determine if the different disease mechanisms lead to similar or different patterns of neuroinflammation, similar or different disruptions to the connectivity of the neurons in the brain and, finally, different or similar breathing patterns.

“We have animal models of the different types of injury and inflammation, and, importantly, the constantly-expanding capability to assess electrical recordings to quantify connectivity in the brain,” says Dr. Jacono. “This is some of the more novel approaches employed in the grant from a neuroscience-type research perspective."

This four-year, preclinical grant launched September 2022. Dr. Jacono has a multidisciplinary team of colleagues working with him, including Yee-Hsee Hsieh, PhD, Thomas E. Dick, PhD and Rishi Dhingra, PhD from Case Western Reserve University (CWRU) in Cleveland, as well as Mathias Dutsschmann, PhD, who will be moving his research program to CWRU from the University of Melbourne, Australia in January 2023.

Clinical Applications

Personalized medicine. Dr. Jacono says clinicians hypothesize that inflammation in the brain contributes to problems with delirium, a big challenge in the ICU for patients with these diseases.

“This is the personalized medicine aspect and the overarching goal of this project,” he says. “It will help us understand in pre-clinical or animal models what’s happening. The knowledge we gain from these studies will allow us to translate non-invasive markers of illness severity to clinical trials in humans, and then help bedside clinicians make better decisions about escalating care or implementing appropriate therapies.”

Risk stratification. Clinicians experience significant information overload in the ICU, with invasive monitors providing second-by-second patient monitoring.

“This can become overwhelming to humans and a lot to process when you’re caring for multiple critically ill patients,” says Dr. Jacono. “Early warning scores for things like sepsis and acute lung injury have been developed. However, these alerts can be non-specific and repetitive, so alarm fatigue sets in. We want to improve the automated alerts and make them more sensitive and specific to the problem, so clinicians focus on the right patient at the right time.”

Dr. Jacono also hopes to develop additional biomarkers that complement standard vital sign monitoring, with the goals of delivering patient care more efficiently and precisely.

Improve Clinician Decision Support. “There is information contained in the patterns of breathing and heart rate that are not captured by looking at the average heart or breathing rates, which is what most of the prognosis and alert scores use,” says Dr. Jacono. “We might have two individuals who have different patterns, and these patterns tell us which patient is more sick than the other. However, the patterns are not easily observed. A computer can process patterns and extract and present pertinent information to help clinicians make better decisions by giving them more actionable information.”

Ultimately, this grant will help clinicians have a better understanding of critical changes in patterns so translational measures can be developed and implemented in the hospital setting.

For more information about this study, call Dr. Jacono at 440-870-9351.

Contributing Expert:
Frank Jacono, MD
Chief, Division of Pulmonary, Critical Care & Sleep Medicine
Virginia Hubbell Chair in Pulmonary and Critical Care Medicine
University Hospitals Cleveland Medical Center
Professor
Case Western Reserve University School of Medicine