Before the 1950s, it was rare for a baby born with cystic fibrosis (CF) to survive to more than 5 or 6 years of age. In 1962 the median survival was about 10 years with few surviving into their teen years, according to the National Institutes of Health. During the 1980s, the average lifespan increased to 14-20, and today, thanks to dramatic improvements in the medications used to treat the disease, it’s 37, with many patients living into their 50s and 60s.
But those are only numbers for 42-year-old Marissa Benchea, diagnosed at birth with CF, an inherited disease of the mucus and sweat glands primarily affecting the lungs, pancreas, liver, intestines, sinuses and sex organs. Benchea has been a patient at Vanderbilt since she was 15.
Benchea is one of hundreds of thousands of adults not only surviving but thriving with a chronic childhood disease — thanks to improved medications, treatments, interventions and medical surveillance.
An isolating and invisible disease
Patients in the adult CF program at Vanderbilt range in age from 18 to 76, although patients in their 70s usually have atypical CF, a milder form diagnosed later in life, said James Tolle, MD, assistant professor of Medicine.
Today’s longer life expectancy can be linked to many improvements in care, starting with earlier diagnosis. Since 2008 every child born in the U.S. is screened for CF within 24 hours of birth.
And there have been numerous improvements to baseline therapy for patients, including pancreatic enzyme replacement for nutrition. CF patients diagnosed decades ago would often die of malnutrition, Tolle said. Other improvements include better airway clearance techniques, medications that help break down the thickness of their mucus and the development of azithromycin, an oral antibiotic that can help reduce inflammation and the progression of the disease.
“By the time children with CF reach adulthood they’re much healthier than they used to be,” Tolle said.
The past decade also saw the introduction of modulators, oral medication designed to improve the function of the CFTR protein, the abnormal protein in CF that leads to thicker secretions and developing lung and pancreatic disease.
“Most likely in the future, the use of modulators is going to improve lifespan and decrease severity of the disease and, we would assume, the progression of the disease,” Tolle said. “So, we don’t really know the long-term effects would be on a child started on modulators today.”
Tolle cautions, however, that with an increased lifespan comes other health issues.
He predicts there will be a larger group of CF patients with diabetes, and patients will continue to grapple with infertility — about 97 percent of men with CF have infertility due to the lack of development of the vas deferens. Women also have reduced fertility due to the thickness of the cervical mucus.
Mental health will also continue to be a major issue, he said. CF patients have a higher prevalence of anxiety and depression than the general population.
Preparing to transition patients to the adult program begins early. “Transitioning from childhood to adulthood takes time — graduating from high school, going to college, getting a job, moving out of your parents’ house — it doesn’t happen in a day, and neither does transitioning from our pediatric to adult program. It’s an area we’re all focused on, looking at quality improvement and making sure the transition goes as smoothly as possible,” Tolle said.
Benchea considers herself a “full-time patient.” She worked for nonprofits in program development until about eight years ago, then lost both of her parents to cancer. “Life events caused my health to tank. I was sick more than I was healthy,” she said.
She no longer works full time but volunteers as a patient advocate for people with CF at both the local and national level and has helped develop programs for the National CF Foundation, including Breathe Con, a virtual program for adults with CF where they can be together online and away from germs.
“It’s an extremely isolating illness and an invisible disease because it’s not always apparent that someone with CF is sick,” Benchea said. “And people are at such different phases. You can have a 20-year-old waiting for a transplant and a 40-year-old with a family and working. But we’re all facing the same thing and we have a huge treatment burden.”
It’s often difficult for CF patients to work, Tolle said. “Some can’t work in certain environments because of irritants to their lungs. Some can’t hold certain jobs if they can’t do their treatments at work. They have to see multiple doctors and that means time away from work.”
Benchea faces about four hours of lung therapy to break up mucus each day — two in the morning and two at night, with sometimes extra treatment in the afternoon. “It’s so time consuming and so rigorous. Every day is a hurdle and you can still feel horrible and be sick. You don’t get breaks. You can’t skip a treatment, or you feel it, or you can do all the treatments and you may still feel horrible.”
A new population
Melinda Wyrick, 37, represents another group of patients living longer lives — those with serious congenital heart diseases and malformations.
Wyrick was born with aortic stenosis, the thickening and narrowing of the aortic valve. On Dec. 13, 2017, she delivered twins about four weeks early by cesarean section. Her obstetrician asked her if she wanted to know the gender of the babies before she was put under general anesthesia. Although it wasn’t said, Wyrick knew it was in case she didn’t survive the operation. “You have one of each,” Jennifer Thompson, MD, assistant professor of Obstetrics and Gynecology, told her.
A team of 27, ready to deliver Arabella Snow and Charleston “Rhett” Wyrick, cheered. Many were on hand to carefully monitor and support their mother’s heart during her C-section.
“Fifty years ago, 25 percent of people with complicated heart disease survived. Now the number is 85 percent,” said Ben Frischhertz, MD, assistant professor of Medicine and Pediatrics and director of Vanderbilt Heart and Vascular Institute’s adult congenital heart disease program. “But there’s a new population of people with manmade disease — disease resulting from having these interventions earlier in life. We have this new population of survivors who need ongoing care as they reach adulthood and beyond,” he said.
To keep up with the number of patients with disabilities and serious chronic illnesses who are reaching adulthood, there’s a need to educate primary care physicians who will be caring for many of these patients, said Jeffrey Neul, MD, PhD, director of the Vanderbilt Kennedy Center, a national disability research, training and services center. “It’s not practical to imagine that all the children’s hospital specialists in the world will follow these people indefinitely. We need a larger workforce. And I don’t think we will ever be able to train enough subspecialists to meet the ultimate need,” he said.
“The transition to adulthood for all childhood diseases is very challenging. The CF community has developed a great model of patients not living in the children’s hospital forever. They go to an adult provider who understands CF. That’s the model we’d love to see for all chronically ill patients and those with disabilities. Ultimately, most of the care will need to be provided by the primary care physician, and we need to create systems and educational opportunities for adult care providers to give them information and knowledge about these diseases so they feel comfortable providing general medical care for them.”
A one-time shot
Wyrick’s aortic stenosis has been controlled with constant surveillance including cardiac catheterizations and ultrasounds, medication until she was 22, then a healthy diet, no caffeine and limited sugar. She had an arrhythmia that was finally eradicated with an ablation in 2016, after a failed attempt when she was a teenager.
“I was told at 15 not to conceive, that I wouldn’t make it through a delivery, but I always wanted a family even if it meant adopting, and I never gave up hope that I’d carry a pregnancy,” said the Murfreesboro, Tennessee, resident. Years later, with the help of a fertility specialist, she got the OK from Frischhertz, her cardiologist, to try to conceive. Under the supervision of her obstetrician and the Maternal/Fetal Medicine program in the Department of Obstetrics and Gynecology, she started taking the fertility drug Clomid.
The Junior League Center for Advanced Maternal Fetal Care offers a collaborative clinic for women with serious chronic illnesses who are considering pregnancy, are pregnant, or are postpartum.
Wyrick got pregnant within six months and the babies were checked to make sure they didn’t inherit her heart condition. They had healthy hearts with no signs of disease. Wyrick wanted to deliver vaginally with no pain medication, but “they laughed me out of the office,” she said. “Finally, I got it that we couldn’t push too hard and stress my valve, so my family and I talked, and we decided to err on the side of caution. The only bad thing is that since this had to be an intubated cesarean, and probably my only pregnancy, my husband would not be able to see his children born.”
Arabella and Rhett were delivered at 32 weeks gestation weighing 4 pounds, 12 ounces each, and Wyrick did well though the surgery. “The team did such a great job of keeping an eye on my heart,” she said. “You could see it in all of their faces — nobody could believe I could do this without complications. Even to the smallest detail, this was a perfect delivery. Everybody knew this was probably a one-time shot and they helped make it symbolic and memorable.”
Frischhertz said there are now more adults with congenital heart defects than children worldwide. Physicians are just now seeing the first adults to survive hypoplastic left heart syndrome, for example, a serious defect in which the left side of the heart is underdeveloped.
“These babies only started surviving in the 1980s and 90s and having adults with this heart disease is a completely new problem that many of us have never seen before,” he said.
As time goes on and new techniques and tools are developed, surgeons are going to be getting better at repairing hearts, leading to even more adult survivors of congenital heart defects, Frischhertz said.
“Our surgical techniques have improved since open heart surgery came along in the ’50s. And everything has improved on the medical side. Our perfusion with heart bypass, anesthesia, ICU care and cardiology and imaging techniques are better than ever. All of this, but especially the surgical innovation, has contributed to better survivorship.”
Another aspect of cardiac care that is helping boost survival rates is transplant, Frischhertz said. Vanderbilt performs more heart transplants than any other program in the Southeast, with patient outcomes among the best in the nation.
There are technical challenges of transplanting an adult who has had multiple operations and an abnormal anatomy, he said. “Each transplant requires much planning and interdisciplinary collaboration. Our surgeons and cardiologists on the pediatric side are collaborating with those on the adult side to provide the best care for this group of patients.”
Adults with serious congenital heart defects often suffer from anxiety disorders. Young adults with serious chronic illnesses often carry the burden of their illness with them years later, struggling with physical and emotional problems as adults, less likely to achieve the same level of education or employment as their healthy counterparts, according to a research study from the University of North Carolina at Chapel Hill.
“Children with chronic diseases worry about dying. Some struggle holding a job, or if they’re in school, completing assignments. Taking care of themselves can be challenging,” Frischhertz said.
Adulthood is a time for developing independence from parents, and children growing up with a serious chronic disease can struggle to be independent, he said. “When you’re 18, you don’t want to be taking medications, scheduling appointments, calling doctors. Just the things you need to do to stay healthy are hard to maintain when you’re doing it for the first time on your own.”
Social, sweet, stubborn
Linda Prader, of Paris, Tennessee, describes her daughter Ashley, 25, as a people person, very social and sweet.
“But she’s also a cute little redhead, so she can be stubborn,” Prader affectionately says of Ashley, who has Down syndrome.
Half of all people with Down syndrome are born with heart defects, and Ashley was born with tetralogy of Fallot and had surgery at Vanderbilt Children’s Hospital when she was 6 weeks old.
The rare congenital heart condition is caused by a combination of four heart defects that are present at birth which affect the structure of the heart and cause oxygen-poor blood to flow out of the heart and to the rest of the body.
“We were told early on that she might not ever roll over, walk or talk, and she was sent home with a feeding tube, but she walked, talked, did everything normally. She reads. She helps me with my cell phone. She’s very high functioning. We’ve been blessed.”
Ashley is artistic, making 3D images by combining stenciling with lines behind them to give a 3D look, and painting wooden birdhouses, cathedrals and other designs. She works one day a week at Sweet Jordan’s, a local bakery whose owners have a child with Down syndrome. The owners hire adults with disabilities to help at the bakery and are opening a coffee shop next door that will share employees.
Neul, the Vanderbilt Kennedy Center director, said most of the one in five children who have a developmental disability will become adults.
Adults with Down syndrome are at a higher risk for developing Alzheimer’s disease.
“We have a pretty good sense of why,” Neul said. “On chromosome 21, the chromosome there’s an extra copy of in Down syndrome, there is also a gene (APP) that is a risk factor for Alzheimer’s. Since people with Down syndrome have three copies of that chromosome, they’re at an increased risk.”
Neul said children with Rett syndrome, his area of specialty, are also surviving longer into adulthood. A genetic disorder that primarily affects girls, individuals lose the ability to speak and use their hands and have difficulty walking. Changes to a more aggressive type of care for these patients, including better nutritional support, have led to longer life expectancies.
And as they reach adulthood, they are often treated by health care professionals who are not as familiar with the disorder. “We’re only beginning to learn about changes with aging in these disabilities and understanding more about what we should worry about, what we should consider and look for,” Neul said.
Adults with Rett syndrome can develop Parkinson’s-type features and changes in motor function and their ability to walk and initiate movement.
The Vanderbilt Kennedy Center is working to create systems and educational opportunities both for adult caregivers and for providers of adult health care to gain information about intellectual or other developmental disabilities so that they can feel comfortable caring for the increasing numbers of patients who will be seen in their practices.
One system, the IDD Toolkit for primary health care providers, helps educate the workforce about health disparity faced by persons with intellectual and other developmental disabilities.
Parents of children with a significant intellectual or developmental disability always have one eye on the future.
“It’s important to recognize that your children with disabilities could outlive you and to think about who and how additional support will be provided when you’re no longer there. We encourage parents to discuss guardianship early. It’s a complicated discussion because it’s not always simple. You should be thinking about this before the teen years,” Neul said.
Ashley Prader’s father died five years ago and Prader, 57, has determined that Ashley’s aunt in Illinois will be her guardian upon Linda’s death.
Ashley worries about something happening to her mother, Linda said. “I told her not to worry; I have it worked out.”
Benchea, who has been taking part in Vanderbilt clinical CF trials since she was 15, is currently enrolled in another trial that keeps her traveling back and forth for the expert care she needs. But she doesn’t mind the driving.
“I have a full life and lots of friends and family, and I’m pretty independent. It hasn’t been in my cards (to get married). If somebody comes into my life, I’ll be ready, but it takes a special person to be in a relationship with someone with a chronic disease.”
Despite the ups and downs of her disease, she considers herself fortunate.
“I love my life. I’m lucky for someone at 42. I’m such an old lady with CF,” she laughs. “I’m not on a transplant list. I’m not on oxygen. I don’t have the stress of a job because I’m not working. If I lose sleep, I can recover the next day,” she said.
Benchea said she is cautiously excited about the future and some of the treatments on the horizon. “I feel fortunate that research and science have kept me alive, and as new breakthroughs in science keep happening, I am hopeful that I will lead a full and independent life despite having CF.”