Despite Breakthroughs, Cystic Fibrosis Answers Remain Elusive

Over 60,000 people worldwide have cystic fibrosis, nearly half of them in the US. Cystic fibrosis (CF) is an inherited disorder that affects the respiratory and digestive systems of children and younger adults, robbing them of breath and of the ability to create energy from food.

Julie A. Biller, MD, Associate Professor of Medicine at the Medical College of Wisconsin, specializes in CF and pulmonary medicine. Dr. Biller works with CF patients over age 12 at the Pulmonary Medicine Clinic at Froedtert & Medical College and at the Children's Hospital of Wisconsin Pulmonary Clinic.

“The highest incidence of the disease is among Caucasians with roots in Central or Northern Europe,” says Dr. Biller. “Folk tales from that area predicted that babies who tasted salty to their mothers’ kisses would not live long. That’s perhaps the earliest description of CF, because, in general, those with CF do tend to have saltier sweat.”

It wasn’t until 1938, though, that Dorothy Anderson, MD, a pathologist at Columbia University, published the first clinical descriptions of CF. In those days, children with CF usually died in infancy. With medical advances and a more complete understanding of the disease, the lifespan of CF patients has steadily increased. “A computer model now anticipates a median survival age of 40 for a child born with CF today,” says Dr. Biller.

Respiratory and Digestive Difficulties Common
“Most people with CF have recurrent lung and sinus infections,” says Dr. Biller. “So in childhood, some of the most frequent symptoms are cough or repeated bronchitis, pneumonia and sinusitis.” Over the years, repeated infections take their toll on patients’ lung tissue, and lung failure is a common cause of death.

In addition to respiratory symptoms, 85% of those with CF have pancreatic insufficiency, preventing digestive juices from entering the stomach to break down food. This results in weight loss, malnutrition and frequent and foul-smelling bowel movements.

Other symptoms can include nasal polyps, rounding and enlargement of fingers and toes, coughing of blood, enlargement of the right side of the heart, abdominal pain, gas and rectal prolapse. Some with CF suffer from liver disease, diabetes, inflammation of the pancreas, and gallstones.

Genetic Breakthroughs
“The CF gene was identified through some very new, cutting-edge technology in 1989,” explains Dr. Biller. “By itself, the molecular genetic procedures that were developed to find the CF gene revolutionized our knowledge and information about other genetic disorders. From that standpoint, CF really is a landmark disease.”

Herein lies the basic mystery. “We know the genetic abnormality behind CF and we know the biochemical abnormality it causes, but we don’t know exactly why people with CF develop lung disease,” says Dr. Biller.

CF exhibits what is known as a “recessive” pattern of inheritance. “This means you have to have two copies of the abnormal gene – one from each parent – to have the disease,” says Dr. Biller. “People with one copy of the abnormal gene are called ‘carriers,’ and they show no symptoms. Carriers frequently have children without knowing they have the CF gene.”

The pattern of inheritance for CF works like this: Each time two carriers reproduce, their chances of having a child with the CF gene are one in four. There’s also a one in four chance the child will not carry the CF gene. Chances are two in four that their children will be carriers.

The severity of the disease varies widely among patients. “At least 1,000 known CF genes exist,” says Dr. Biller, “and not everybody has the same genetic abnormality – some are mild, some more severe. But we can’t always tell by looking at patients’ genes who will have mild CF and who will have severe.”

Because Wisconsin participates in newborn screening for CF, the usual age of diagnosis here is six weeks compared to about 12 to 18 months nationally, according to Dr. Biller.

Four Categories of Treatment
The four broad categories of CF treatment are nutritional, airway clearance, medication, and, when possible, lung transplantation.

“Because most CF patients suffer from pancreatic insufficiency, nutrition is crucial,” says Dr. Biller. "We’re very diligent about making sure our patients eat enough so they have sufficient calories to maintain their body weight within fairly narrow ranges,” says Dr. Biller. “If people have trouble with that, we give them nutritional supplements to take orally or through gastrostomy tubes as they sleep.” There are also medications to help take over the function of the missing pancreatic enzymes.

“We teach a variety of airway clearance techniques to help CF patients clear thick, infection-laden mucus from their airways,” says Dr. Biller. Most techniques incorporate the use of breathing devices to shake the breathing tubes and loosen the mucus, along with coughing, or forced expiration, to expel material from their lungs.

Antibiotics, medications to loosen airway secretions, and anti-inflammatories are used to treat CF. “The newest delivery method for antibiotics is through a nebulizer, allowing patients to inhale medication directly into their breathing tubes,” says Dr. Biller. ”Antibiotics can also be used orally or intravenously if people become very ill.”

“The newer advances in CF are in medications using recombinant technology to help loosen airway secretions,” says Dr. Biller. “That involves taking normal enzymes or proteins that have been produced in our bodies, putting them into microbes to get larger amounts of them, and then having patients inhale them to thin and liquefy the mucus. One medication used to loosen mucus is Pulmozyme, or DNase.”

Anti-inflammatory medications like the inhaled corticosteroids used for asthma patients are also used to treat CF patients. “There is also new information about the antibiotic Zithromax (generic name azithromycin), says Dr. Biller, “which appears to have an anti-inflammatory property. Some patients are also on high doses of ibuprofen.”

Lung transplantation, Dr. Biller explains, is the last potential option for CF patients.

Medical College Research Continues
The Medical College and Children’s Hospital are participating in an ongoing study funded by the National Institutes of Health (NIH) to examine the efficacy of the CF newborn screening program. The study seeks to determine whether early intervention actually delivers a better outcome and whether it’s cost effective.

Medical College investigators are also looking at the development of pseudomonas antibodies. "Pseudomonas is a particularly nasty germ that people with CF are prone to having in their respiratory systems," Dr. Biller says. "The goal of the NIH-funded study is to determine whether it’s possible to come up with a vaccine to prevent these germs from taking hold."

Other Medical College of Wisconsin investigators are trying to determine the exact composition of a thin layer of fluid that bathes the airways. Patients with cystic fibrosis exhale into glass tubes so the composition of the exhaled gases can be studied. This non-invasive method might give us answers about the lung damage characteristic of cystic fibrosis.

Living with the Disease
“We provide our patients, their families, schools, religious organizations and others with educational material to help them cope with the disease,” says Dr. Biller. But she doesn’t minimize the level of care needed for CF patients to remain healthy. “Every time most CF patients want to eat something, they need to think ahead and take a couple of pills beforehand. Patients are also on other medications, and we expect them to do airway clearance twice a day, which takes 15 to 30 minutes each session.” CF patients also must visit their clinic regularly and can suffer periodic illnesses or hospitalization.

“On the whole, many people with CF live fairly normal lives,” Dr. Biller says. “We tell CF patients to live one day at a time. Nobody knows the number of days they’re given, so we can only try to make the most of each.”

Judith Halvorsen
HealthLink Contributing Writer

This article includes information from the National Institutes of Health.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.