Although cystic fibrosis (CF) has long been known as a pediatric disease, physicians and scientists at Vanderbilt University Medical Center are providing specialized care for an ever-growing population of adults with CF, as well as conducting targeted research expected to improve treatment for these patients.
For the first time since CF was identified as a genetic disease in the late 1930s, adults with the disease now outnumber children as improved therapies and research discoveries have resulted in longer life expectancy. In 1980, the average life expectancy for CF patients was around 18 years. Now, the average life expectancy for CF patients in the United States is just over 37 years, according to the National Institutes of Health (NIH).
CF is a progressive, inherited disease that causes the body to produce thick mucus that compromises the function of organs, including the lungs, pancreas, liver and intestines. Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the disease. Nearly 2,000 CF-related genetic mutations have been identified, making it challenging to target the disease with widely effective treatment. While there is no cure, a long list of therapies are used to manage symptoms and slow the disease’s progression.
“Multidisciplinary care is critical when it comes to caring for CF patients,” said James Tolle, MD, director of the Adult Cystic Fibrosis Program at Vanderbilt. “Within our core CF team, we have physicians who are pulmonologists, a nurse practitioner, nurses, a social worker, dietitians, physical therapists, a specialty pharmacist and a respiratory therapist.
“We also collaborate with other specialties at the Medical Center, referring patients most often to endocrinology for treatment of CFRD (cystic fibrosis-related diabetes) and to otolaryngology for sinus issues. This is not a simple disease.”
Bonnie Slovis, MD, professor of Medicine, emeritus, established the Adult Cystic Fibrosis Program at Vanderbilt in 1998, one of the first such specialty clinics in the country. Today, 280 adult CF patients from a multistate region are seen routinely at VUMC’s adult program. Most patients return every three months, said Tolle. In addition, approximately 220 patients are seen at the Cystic Fibrosis Pediatric Program at Vanderbilt, according to Rebekah Flowers Brown, MD, director of both the Cystic Fibrosis Center at Vanderbilt and the pediatric CF program at Vanderbilt.
But living longer can be a paradox for CF patients, he added. As the disease progresses over a longer period of time, organ damage builds, leading to new challenges such as the most common complication, cystic fibrosis-related diabetes. CFRD affects nearly half of adults with CF. Screening for CFRD begins at age 10, and about 20-25 percent of CF patients are diagnosed with CFRD before they reach adulthood, said Brown.
Research related to CF in adults is a fledgling field because this patient population simply did not exist until life expectancy improved, Tolle said. Despite this, significant advances in CF care are a direct result of research discoveries, such as pancreatic enzyme replacement therapies that improve digestive function, which have been a key therapy since the 1980s-90s, and drugs called CFTR modulators, first available clinically in 2011. CFTR modulators correct the malfunctioning protein produced by the CFTR gene to better regulate the flow of water and chloride in the lining of the lungs and other organs.
“Now, as we have more adult patients being diagnosed with CF-related diabetes, it’s crucial that research be done in this area,” Tolle said. “Otherwise, we’re just going off of anecdotal reports. As we collect more data over years and years, we certainly hope it results in our being able to take better care of these patients.”
The Cystic Fibrosis Center at Vanderbilt, including both the pediatric and adult programs, is part of the Cystic Fibrosis Therapeutics Development Network (TDN), a CF clinical trials network that unites experts to conduct multisite clinical studies to develop and evaluate new therapies, Tolle said. Tolle and Brown are the co-principal investigators for the grant funding received from the TDN.
Studies related to CFRD are also conducted within the Vanderbilt Diabetes Research and Training Center (VDRTC), a NIH-sponsored Diabetes Research Center lead by Alvin C. Powers, MD, Joe C. Davis Professor of Biomedical Science.
Most recently, Nathaniel Hart, PhD, a postdoctoral fellow working in Powers’ lab, was lead author on a study published in JCI Insight that suggests CFRD is a result of the loss of beta cells (the cells that produce insulin) and inflammation, rather than a result of catastrophic beta cell dysfunction due to the CFTR gene mutation, as has been a popular belief.
The VUMC study was conducted over five years, and cellular function was analyzed using both mouse models and cells from human pancreata of seven adult CF patients with CFRD obtained through a national donor organ bank. This is the first study using pancreatic islets from individuals with CF.
“Islets — in all forms of diabetes — are damaged or dysfunctional in some way, but when we analyzed cells from these donors we discovered that there are still islets, but that they’re living in a very adverse environment,” said Hart. “This indicates that CFRD is caused by beta cell loss and inflammation rather than islet cell dysfunction as a result of the CFTR mutation.
“What is it about these particular islets that makes them so resilient to stress and able to hang on to their function? This finding is exciting in that it could lead to new direction in terms of what’s being prescribed for CF patients with diabetes.”
“Dr. Hart’s research was from an islet biology perspective, and for the first time we were able to use and study donor pancreatic islet cells from several adult CF patients with diabetes,” said Powers. “Through collaborations with the extremely strong islet biology community at Vanderbilt and investigators in Canada, Massachusetts and Ohio, his research has defined the underlying reason for the impaired insulin secretion in CFRD and demonstrates the importance of studying human tissue and cells.”
