As part of our “Meet Yale Internal Medicine” series, today’s featured physician is Jonathan Koff, MD, associate professor of medicine (pulmonary, critical care, and sleep medicine) and director, Adult Cystic Fibrosis Program.
In his 20-year career, Jonathan Koff, MD, has witnessed a change in the care of patients with cystic fibrosis (CF).
Cystic fibrosis is an inherited disease that causes lung disease, and potentially affects other organs, such as the pancreas. Once considered a “pediatric” disease, CF is changing into a chronic disease because there are now more adults than children with CF. Enhanced treatments and patient care have contributed to these improved outcomes, which has resulted in over 30,000 Americans with CF in a national registry.
Koff decided to pursue the pulmonary field due to his interest in CF, asthma, and chronic obstructive pulmonary disease (COPD). He completed his residency in Rhode Island, and moved to California to complete a fellowship in pulmonary and critical care.
“During my fellowship, I was struck by the impact of chronic infections and was really interested in how to treat patients with some of the complicated infections, such as multi-drug resistant pseudomonas, and non-tuberculous mycobacteria,” explained Koff. “I also began to identify adult patients with atypical CF, and I was struggling with what course of treatment was most appropriate for them. Early in fellowship, I was approached by the Director of the Adult CF Program to join her clinic to develop expertise in CF. In addition, I was able to bring those atypical patients to this clinic to better characterize and treat them.”
Koff also became an expert in lung transplantation while in Calif. by completing extended fellowships in CF and lung transplant. At this time, Yale School of Medicine and Yale New Haven Hospital (YNHH) do not have a lung transplant program, but he ‘hopes to participate in’ such a program in the future.
Koff came to Yale in 2011 to direct the Adult Cystic Fibrosis Program, to develop his own laboratory research program, and to be closer to family. Recently, this work has resulted in a potential breakthrough in CF care, thanks to a collaboration with Yale colleagues Benjamin Chan, PhD, associate research scientist, and Paul Turner, PhD, Elihu Professor of Ecology and Evolutionary Biology in the Department of Ecology & Evolutionary Biology, and department of biological & biomedical sciences.
This collaboration began because Chan and Turner developed a strategy to use bacteriophages (phages) to target pseudomonas, a bacteria that is a common pathogen in CF patients. In September 2018, Koff worked with Chan and Barbara Kazmierczak, PhD, MD, Gustavus and Louise Pfeiffer Research Foundation M.D.- Ph.D. Program Director and professor of medicine (infectious diseases) and of microbial pathogenesis, to treat a patient with multi-drug resistant pseudomonas in YNHH’s Medical Intensive Care Unit with inhaled phage therapy through an Food & Drug Administration emergent indication mechanism. Since then, Koff and colleagues have treated CF and non-CF bronchiectasis patients in the hospital and in Winchester Chest Clinic.
“We are seeing some potentially positive results with phage therapy, which has led us to develop clinical trials and submit additional grant funding,” said Koff. “Most of this work is in the CF space, but it has the potential to more broadly benefit other patient populations.”
“Improved CF outcomes are the result of new ‘modulator’ therapy, which is an example of personalized medicine for CF patients,” Koff said. Modulators are drugs that can target specific CFTR gene mutations to improve their function.
“If a patient has a mutation that could be targeted by a modulator, you could imagine where we could change their disease trajectory,” he explained.
There are over 2000 variants in CFTR that may cause CF. These findings have contributed to identifying individuals with a milder type of CF. One specific patient was diagnosed at age 75 with a classic presentation of CF with bronchiectasis that likely developed in his 50s. Genetic testing of this patient found new, previously unidentified CF gene variants.
“There is a lot of optimism for individuals with CF right now,” said Koff. “In an ideal world, with the use of modulators and phage therapy, we may be able to move lung transplant out farther and farther. It’s just been a phenomenal time in my career to have taken care of people before modulators and now. Directing the Adult CF Program at Yale, partnering with my outstanding team, caring for our patients with modulators and now the potential of phage therapy, and seeing them collectively to do better than we have seen historically is very exciting,” Koff said.
“Obviously, a CF cure is what we aspire to. However, with these therapies, patients can better manage their lung disease and have an improved quality of life.”
Given these improved outcomes, there will be a need for additional pulmonary physicians, said Koff, due to the growing CF population.
“We will continue to find milder forms of CF and will do a better job of finding those patients because of the ability to do genetic testing. Since the population will grow, we will need more providers. I am obviously biased but we have a ton of opportunities in this area. It is incredibly exciting.”
For more information on Yale’s Adult CF Program, visit Yale Adult Cystic Fibrosis Center.