Traversing the 'jungle' of lung transplant viruses

During the first year of any lung transplant, infection can be the leading cause of death. Brian Keller, MD, PhD, is the director of the College of Medicine’s Lung Transplant Research Group at The Ohio State University. He’s studying viruses and the role they play in how certain microbes can have a long lasting impact on patient health.

Lung transplants have become the standard of care for end-stage diseases and more than 4,500 were performed worldwide in 2017. Not all transplants are successful, however. Dr. Keller reports that 50 percent of recipients have some degree of chronic rejection within five years after transplantation. After the first year, graft failure is the number one cause of mortality, and microbes play an important role there as well.

Certain microbes identified in the months after transplant can have long-lasting consequences. Respiratory viruses such as influenza, coronavirus, parainfluenza virus, and others; bacteria like Pseudomonas; and fungi like Aspergillus have been linked to later development of chronic rejection.

The “jungle” of viruses is a thick and difficult one to traverse. “Infections are so serious, and so common, among lung transplant patients that we approach the issue from every angle we can,” Keller said. 

Studying viruses has been a long-time passion for Keller. “My passion for viruses and their role in health and disease started with the movie ‘Outbreak’,” he said. “Early on, after reading ‘The Hot Zone’ and ‘Level IV Virus Hunters of the CDC,’ I wanted to be that person venturing into the jungles to discover new viruses. Now, with today’s technology, we can more easily search for new viruses in the human body.”

Viruses are a major cause of infection. Lung transplant patients are especially susceptible to viruses because they take medications to suppress their immune systems to prevent graft rejection. “To try to protect our patients, we make sure their vaccinations are up to date,” Keller said.

Beyond that, his team has several research projects underway. Ohio State has three active clinical trials exploring novel treatments for chronic rejection after lung transplantation. A recent study tested a new antiviral medication for treating a specific infection called “cytomegalovirus” (CMV). The new medication, letermovir, controlled CMV as well as previous treatments while reducing the side effect of low white blood cell counts.

One exciting telemedicine project gives transplant patients the ability to monitor their lung function from home. A handheld device called a “spirometer” has a mouthpiece that patients blow into. A mini-turbine detects air flow and a computer calculates function parameters. The information is relayed via Bluetooth to the patient’s mobile device and to a cloud-based storage system. There, the transplant team can access it in real time and receive alerts of any potential trouble with the lung transplant. 

Keller has just received a grant to validate in lung transplantation, another technology that is currently used for kidney and heart transplants. When a transplanted organ is damaged, some of its DNA spills into the recipient’s bloodstream. The technology being tested uses that DNA as a marker for potential allograft (transplant) rejection and infection.