Surviving cystic fibrosis

The genetic revolution didn’t save her. That took a double-lung transplant.

Roger Lemoyne/ Denise Grant/ Maclean's archives

Anyone driving along Highway 401 west to Toronto from Montreal on Oct. 6 would never have known Caroline Donelle had turned her red Honda Civic into a hospital room on wheels. In the trunk were five oxygen tanks and stashes of painkillers. Donelle kept thinking, please don’t let anyone rear-end me.

In the backseat was her daughter, Ashley, then 24, shrouded in a thick comforter, pillows and tubes, wafting in and out of consciousness. Diagnosed with cystic fibrosis as a baby, Ashley had defied expectations—reaching adulthood, attending university, travelling, even having a daughter, Leila.

Now though, her lungs were clogged and damaged with thick mucous, and her lung function was at an all-time low of 11 per cent. “I knew, I could feel it,” recalled Ashley recently from her apartment just outside of Montreal, “I was dying. I wasn’t coming out of it.”

A double-lung transplant is the only hope for CF patients who get as sick as Ashley was, and that procedure comes with a whole new set of complications and risks, including death. Ashley, who had been in and out of hospital for months as doctors tried unsuccessfully to get her disease under control, had been approved to have the surgery in Toronto, where wait times are shorter.

But just before she was supposed to leave Montreal for a preoperative assessment, Ashley took a serious turn for the worse. Doctors urged mother and daughter to re-book the appointment. They refused. Instead, Donelle packed up her car and, against medical advice, had Ashley released from the hospital. “I didn’t want her to miss this chance to get saved,” Donelle says, sitting across from Ashley at the kitchen table. “We had nothing to lose and everything to gain.”

Today, several months after her double-lung transplant, Ashley barely recalls the six-hour trip to Toronto, never mind the weeks before and after surgery. “I think it’s because I was oxygen-deprived, ” she half-jokes. Her mother, on the other hand, can’t shake the memory. “I remember that drive well,” Donelle says, “because I was scared. I’d occasionally reach back to feel if she was still warm.”

No one could have foreseen this future when Ashley appeared on the cover of Maclean’s in mid-July 1991 as a six-year-old astride her bike, smiling. “A genetic revolution” was written in bright-white type. “Why Ashley Dyer hopes to survive cystic fibrosis. The promise of new ways to treat fatal diseases.” Researchers had identified the gene responsible for CF, and the scientific community was ecstatic, certain even, that soon the disease would be annihilated.

Unfortunately, 19 years later, there is still no cure for CF. “There never was a genetic revolution,” says Donelle matter-of-factly. “Despite all the medical advances that have been made, there’s still no fix,” adds Ashley. “Even the transplant is only going to buy me time. I’m happy to have the time. If I live another 20 years, I’d be thrilled. If in two years I need another transplant, we’ll cross that bridge when we get there. But the fact that this illness is still there, it’s just an awful thing.”

That CF hasn’t been cured since Ashley became the de facto cover girl for the disease is not for lack of trying. Early on, scientists believed that gene therapy would solve the problem. The basic idea was to inject a good copy of the CF gene into a virus, which would then transfer it to the lungs. “Then presto, you have a cure,” says Dr. Francis Collins, one of the co-discoverers of the CF gene. Now, as the director of the National Institutes of Health, the federal biomedical research agency in the U.S., Collins looks back and says, “We were pretty naive.”

The hitch was twofold, Collins says. Gene therapy wasn’t very efficient; every cell needed to be replaced in the lung, but scientists couldn’t figure out how to make that happen. What’s more, the immune system proved too good at its job of fighting viruses—after a few days or weeks of gene therapy, it would wipe out the virus containing the good genetic information. All that trial and error, however, wasn’t for nothing. “It’s taken a lot of painstaking research in biochemistry, cell biology, physiology—real basic science,” says Collins, to “now really understand what this gene does, and what’s wrong with it in cystic fibrosis.”

While researchers were learning more about the disease, so too were Ashley and her family. The day she was born, March 14, 1985, doctors realized that Ashley’s intestines were blocked (an early sign of CF) and immediately performed open-bowel surgery. Within 10 days, Donelle and Ashley’s father, Stephen Dyer, were given the diagnosis. “We didn’t know what the hell CF was,” Donelle recalls. “We were thinking wheelchairs. So we went to the library—the books were all from the 1960s—and they said that babies with CF live to be two. I was bawling my eyes out.” In reality, the prognosis was much better—but not great. When Ashley first appeared in Maclean’s, the story noted that “CF usually kills its victims before they reach their 30s.”

Ashley’s treatment over the years was typical for CF patients: daily physiotherapy to loosen the mucous in her lungs, therapeutic breathing masks, and dozens of pills including vitamins and enzymes to support the pancreas and intestines, which CF prevents from properly digesting foods and absorbing fat and nutrients. None of this kept Ashley from enjoying what she says was an otherwise normal, happy youth spent swimming, playing soccer at recess, hanging out with friends in high school, and doing a university exchange to Australia for three months.

But a few times a year, Ashley would wind up in the hospital for two or three weeks on a course of IV antibiotics. Bacteria called pseudomonas would stick to the mucous in her lungs and grow, which made breathing hard. “If you put the mucous in a cup and turn it upside down, it wouldn’t come [out],” explains Dr. Larry Lands, director of the cystic fibrosis clinic at the Montreal Children’s Hospital, and one of Ashley’s physicians since she was 14. At 18, she had her gallbladder removed. At 20, she had a life-threatening blood clot in her lungs. More recently, doctors had taken to sticking a needle in her back to drain the fluid in her lungs. “My pain tolerance is unbelievable,” says Ashley.

Until last year, no matter how ill she became, Ashley always bounced back. “I was in denial for many years about the outcome of CF. I thought, maybe I’m the one in a million that this doesn’t apply to,” she says, referring to the likelihood of dying at a young age.

Cystic fibrosis began to get the best of Ashley last spring, however, when course after course of antibiotics couldn’t clear her infections—since late adolescence she had become increasingly resistant to the drugs. Her lung function kept dropping, from 35 per cent, to 30, to 25. Further complicating the situation was the fact that Ashley was expecting her second child with her boyfriend and Leila’s father (the relationship has since ended). More and more CF patients are having children, despite the infertility that’s haunted previous generations. Better management of CF, and the use of in vitro fertilization, have helped.

In Ashley’s case, she had a natural, healthy first pregnancy and carried her daughter Leila to full term. (Although Leila has one copy of the CF gene, it’s a recessive disease, so a second copy from her father would have been required for her to have CF.) This time, Ashley had been hoping for a son. But as she became critically ill, her body couldn’t cope, and Ashley lost the baby.

By mid-summer, doctors said her only option was a double-lung transplant. Half of lung recipients are alive five years after transplant, but CF patients can survive twice as long or more because, like Ashley, they are usually young. In fact, without those CF-infected lungs, recipients such as Ashley will never die of the disease. While bacteria may still live in their sinuses, and the pancreas and intestines continue to malfunction, the DNA in the new lungs are free of CF.

Knowing this, Ashley and Donelle made that fateful drive to Toronto. At first, Ashley was no better for it. Three days after arriving, she was put in ICU at St. Michael’s Hospital, famous for its CF care, and her family and friends rushed to say goodbye. She was depressed when conscious and in physical agony. But Ashley, whose kitchen bulletin board features a postcard that reads, “Never, never, never give up,” rebounded, partly because of a new antibiotic. The transplant unit put her on the wait list. Within two weeks, she received a call in the night, from Toronto General Hospital a few blocks away, that new lungs were available. Ashley was so excited, “I was hyperventilating,” she says.

Over the next 13 hours, transplant teams removed the lungs from a donor, prepped Ashley for surgery, and wheeled her into the operating room. It was just before 5 p.m. Her mother and father (who divorced 18 years ago) waited in the ICU. Inside the OR, nearly a dozen physicians and nurses assisted Dr. Marc de Perrot, the thoracic surgeon who performed the procedure. He began by taking out the first CF-infected lung that had become bumpy and stiff, and put in the soft, healthy one. For one tense minute, Ashley went into cardiac arrest, but recovered with the aid of a heart-lung machine. De Perrot replaced the second lung, and then, punched roughly 60 staples under her breasts. The operation took almost eight hours.

When word came that Ashley was nearly out of surgery, Donelle sat on the ledge of a window facing the elevators and stared. “Sure enough, around 12:30 a.m., those doors flew open, and out [came] Ashley on a stretcher,” says Donelle. “I could barely see her. There were four or five doctors following the bed. There were tubes and wires everywhere.” But it didn’t matter, Donelle thought. “She’s alive.” It was Nov. 8, she says, “her new birthday.”

To see Ashley today, you’d never know she had CF or a double-lung transplant. Unless, of course, she showed you the scars. Or the dozens of anti-rejections pills, enzymes, vitamins and other drugs she takes daily. Or the thermometer and scale she uses to check for a fever and weight loss, two early signs of rejection. Or the machine she puffs into twice a day to gauge her lung function. “I’m at 90 per cent,” she says, several months after transplant. “I’ve never had that. This is the first summer in my life I haven’t had trouble breathing.”

That’s taken some getting used to. “I had to train my brain that my body wasn’t sick anymore,” she says. For months after surgery, she was afraid to exert herself. She parked near the doors of whatever building she was going to, forgetting she could walk for blocks now. The psychological adjustment has run parallel to the physical trauma of recovery, which has included physiotherapy to build up her strength.

While Ashley adjusts to her new reality, there is a growing campaign to catch CF early through newborn screening for the gene. Several provinces such as Ontario, Saskatchewan, B.C. and Alberta already have such programs, as does the U.S., France and the U.K. Unfortunately, most patients, usually children, are misdiagnosed with asthma or bronchitis before CF is recognized, and by then they’ve already been hospitalized at least once, and experienced poor growth and lung damage.

Scientists now know that there are more than 1,600 mutations that can cause CF. Given that, gene therapy research has mostly shifted from replacing the bad gene to drug treatments that work on the underlying defects instead. Doctors now take a more aggressive approach to eradicating lung infections early with new antibiotic combinations and inhaled meds. There’s more focus on a high-fat diet to prevent the inadequate growth that used to be the hallmark of CF patients. Even better, life expectancy has increased by about one year every year over the last decade—to a median age of survival of 47 in Canada.

But given the long, bumpy road it’s taken scientists to get to this stage, no one is willing to talk about a cure. “I would rather talk about control of the disease because this is a more realistic view,” says Dr. Felix Ratjen, head of CF clinical research at the Hospital for Sick Children in Toronto. “Cure means a one-time hit where you do something and everything is going to be turned back. This is unlikely.”

In another 20 years, Collins says, “I’m optimistic enough to say that it will be a story about a disease conquered,” but what that means isn’t clear. “I do think at that point this will not be a disease that seems so scary and threatening as it has for centuries.”

Today, CF patients around the world, including in Canada, are participating in clinical trials for two pills that could be on the market within a few years that activate alternate cellular channels to compensate for the abnormal ones in CF patients. Early results make scientists such as Ratjen, who is leading a Canadian study of another possible CF drug, “very optimistic that they will make a difference in the way we treat CF patients.”

For now, Ashley is going back to McGill University full-time in September to finish the psychology degree she was too sick to complete a couple of years ago. She goes to the gym up to four times a week and runs on the treadmill. “My legs get tired before I ever run out of breath,” Ashley laughs. She plans on working, attaining her master’s, eventually getting married, and “being Leila’s mom for as long as possible.” Transplant isn’t a perfect cure, but it’s good enough. “If the transplant doesn’t work out, at least Leila knows that I fought, I tried to be with her.”

A few weeks ago, Ashley finally managed to send a personal letter of appreciation to the donor family. “They gave me my life back,” she says. On second thought, she adds, “They gave me a better life than I ever had.” Ashley says the gratitude she feels is indescribable. “There is no word big enough for that.” A sigh of relief—one deep breath—says it all.

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