When our immune system detects an infection or virus, it mounts a defense. But sometimes, this response is too strong and lasts too long, causing inflammation and deadly fluid buildup in the lungs.
Oklahoma Medical Research Foundation scientist Chris Schafer, Ph.D., has discovered how this overreaction might lead to acute respiratory distress syndrome, or ARDS. His work ultimately could result in a medication that prevents or treats ARDS before a patient requires a ventilator.
“Covid-19 is an example of a viral infection that can result in such an overresponse by the immune system that a person ends up on a ventilator,” Schafer said. “When a coronavirus case becomes that severe, a primary cause of death tends to be ARDS, which is excessive fluid in the lungs’ air sacs.”
About 190,000 people are diagnosed with ARDS in the U.S. annually, according to the American Lung Association. Of those, the death rate is as high as 40%. The condition also commonly accompanies sepsis, the body’s overactive and toxic response to an infection, as well as influenza.
During these infections, immune cells travel through blood vessels to the lungs. Doing so requires the vessels to open holes so immune cells can escape to the organ needing the immune response.
“Sometimes those holes become too big and stay around too long and flood the air sacs in the lungs with fluid,” Schafer said. “The ventilator provides oxygen to the body until the immune response stands down.”
Schafer and others are studying how to dampen the immune system’s overreaction. His recent study focused on a protein called ERG that tells blood vessels not to be permeable.
In research models, Schafer discovered that during influenza and sepsis, the body stops producing ERG – but only in the lungs.
“It happens extremely quickly, and it explains why the lungs are so susceptible to filling with fluid,” Schafer. “What we’re after is a way for the body to begin making ERG again as quickly as possible.”
Ideally, that solution would come before a ventilator is needed to keep the person alive. Being placed on a ventilator increases the risk of other problems, such as pneumonia, lung damage, blood clots and secondary infections.
“Dr. Schafer’s research is revealing new information about the mechanisms that regulate how our lungs respond to infections,” said OMRF Vice President of Research Courtney Griffin, Ph.D. “We hope this will eventually help us tip the balance toward fighting off deadly viruses and bacteria more efficiently.”
Following his discovery, Schafer was among 100 scientists nationwide to receive three-year grants through the American Heart Association’s Second Century of Science Initiative. He will continue his study of ERG with the $300,000 award.
Schafer’s research was funded by grant Nos. HL144605 and HL119501 from the National Institutes of Health, PG/10/94/28651, RG/11/17/29256 and RG/17/4/32662 from the British Heart Foundation and CA-831087 from the American Lung Association. The research was published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.
