Cystic Fibrosis

Definition

Cystic fibrosis (CF) is a chronic, progressive and genetic (inherited) disease of the body's exocrine (mucus producing) glands which affects approximately 30,000 children and adults in the United States.

Description

Cystic fibrosis (CF) primarily affects the respiratory, digestive and reproductive systems, as well as the sweat glands. The mucus secreted is very thick and blocks passageways in the lungs and digestive tracts.

Cystic fibrosis is transmitted to a child when both parents carry the recessive gene but do not have the disease. When such a couple has children, there is a 25 percent chance that one of their children will develop cystic fibrosis; there is a 50 percent chance that the child will carry the gene, but will not have the disease; and a 25 percent chance that the child will be totally unaffected.

Cystic fibrosis is the most common fatal hereditary disorder for Caucasians in the U.S. About 1 in 2500 Caucasians are affected, and more than 10 million people (one in 31 Americans; one in 28 Caucasians) is an unknowing, symptomless carrier of the defective gene.

The average lifespan of a person affected with CF is between 28 and 30 years of age. As with any "average" this means that some with this disease now live well beyond this age. With the introduction of medications and drainage procedures, children with CF, who years ago would have died before reaching adulthood, are now often living into mid-adulthood and beyond. The cause of death in CF patients is usually respiratory tract infections or respiratory distress, coupled with enlargement of the right side of the heart (cor pulmonale).

Causes

In 1989, researchers found the defective gene (called delta F508) that causes CF. This gene disrupts a protein (called cystic fibrosis transmembrane conductance regulator - CFTR) that causes the symptoms of CF.

CFTR is made inside the cells (lining the glands) in the respiratory passages, and the small intestine, pancreas and sweat glands. CFTR travels to the cell's surface where it controls the flow of salt (sodium) in and out of the cell. In CF, the CFTR protein is abnormal in a way that prevents it from reaching the cell's surface. Without this flowing process, salt is trapped inside the cells. The body tries to compensate by overproducing bodily secretions such as water, sweat and mucus. These secretions then build up in the body to cause the symptoms of CF.

Symptoms

The pattern of development of CF and the severity of its symptoms varies among individuals. The disease is sometimes obvious soon after birth, but some cases of CF, they are not detected for months (in infancy) or years (in childhood).

In babies and infants, the symptoms of CF are:

• persistent diarrhea

• bulky, foul smelling and greasy stools

• pale stools

• frequent wheezing or pneumonia

• chronic cough with thick mucus

• salty-tasting skin

• poor growth

• blockage of the intestine (called meconium ileus)

• abdominal swelling

• gassiness

• vomiting

• dehydration

In children, the symptoms include:

• frequent respiratory infections

• fever

• cough

• difficulty in breathing

• abdominal pain and discomfort

• gassiness

• fast respiration

• flaring of the nostrils

• poor appetite

• malnutrition

• poor growth

• a barrel-chested appearance

CF can also cause other medical problems, such as:

• sinusitis (inflammation of the nasal sinuses)

• nasal polyps (fleshy growths inside the nose)

• clubbing (rounding and enlargement of fingers and toes)

• pneumothorax (rupture of lung tissue and trapping of air between the lung and chest wall)

• coughing up blood

• enlargement of the right side of the heart (called cor pulmonale)

• protrusion of the rectum through the anus (called rectal prolapse)

• liver, pancreatic and gallbladder problems

• delayed puberty

• reproductive abnormalities (especially male sterility) - Over 90 percent of all males with CF are sterile.

Diagnosis

Diagnosis of CF can be determined at three stages - prenatal, postnatal and early childhood.

In pregnant women, the amniotic fluid surrounding the fetus can be tested for fetal intestinal enzymes. Using a procedure called an amniocentesis, a sample of amniotic fluid is extracted from the amniotic sac (the protective covering around the fetus) and analyzed. In a fetus with CF, the enzymes are decreased.

For newborns, a test called the immunoreactive trypsinogen test (IRT) is administered. In this test, blood is drawn two or three days after birth and analyzed for a specific protein (called trypsinogen). If the trypsinogen levels are elevated, CF is evident.

The most common test for children and young adults is the electrolyte sweat test. This test measures the amount of electrolytes (sodium [salt], potassium and chloride) in a person's sweat. This is done by applying a chemical (called pilocarpine) to the forearm and using a mild electric current to cause the area to sweat. If higher than normal amounts of sodium and chloride are evident, CF is present.

Some of the other tests that can assist in the diagnosis of CF are chest x-rays, lung function tests, sputum (phlegm) cultures and stool examinations.

Genetic Testing

In families with CF, brothers, sisters, and first cousins of the CF patient should be tested to see if they carry a defective gene, especially if they seem to have a chronic lung or digestive problem.

CF tests involve taking any type of tissue, such as white blood cells or cells located in the inside of the cheek, and analyzing the samples for mutant genes. Carriers of the abnormal gene should receive genetic counseling.

Treatment

Currently, there is no cure for CF, but there are treatments for the symptoms of CF, such as lung and digestive problems, hepatic (liver) and biliary tract (gallbladder) diseases, and infertility.

Lung Problems

Lung problems (such as bacterial infections, inflammation and airway blockage) can be treated with pharmaceutical and non-pharmaceutical methods. To treat bacterial infections of the lung, doctors may prescribe antibiotics (such as aminoglycosides - tobramycin [Nebcin or Tobrex]), antipseudomonal penicillins, cephalosporins (such as ciprofloxin [Cipro]), antimicrobial drugs (such as rifabutin - Mycobutin), ethambutol (Myambutol), clarithromycin (Biaxin), clofazimine (Lamprene) and aztreonam (Azactam). Antibiotics may be taken orally, by injection or inhaled (via an aerosol form).

For treating inflammation, doctors may prescribe nonsteroidal anti-inflamatory drugs or steroids, such as ibuprofen (Advil or Motrin) or prednisone. Additionally, pentoxifylline (Trental) has been effective in decreasing inflammation.

For the treatment of airway blockage due to mucus buildup, the doctor may prescribe dornase alfa (Dnase [Pulmozyme]) which is used in an inhalant machine, called a nebulizer.

In conjunction with this drug, doctors advise CF patients to perform bronchial drainage or chest physiotherapy daily. Chest physiotherapy (chest PT) consists of bronchial (or postural drainage), done manually or mechanically.

Manual chest PT can be done in two ways. Autogenic drainage involves using controlled breathing techniques lasting for about 30 to 45 minutes. The other method places the patient in a position that allows drainage of the mucus from the lungs, while at the same time, the chest or back is clapped and vibrated to dislodge the mucus and help it move out of the airways. This process is repeated over different parts of the chest and back to loosen the mucus in different areas of the lung.

There are three airway clearance devices available for use in mechanical chest therapy. The first device is positive expiratory pressure treatment, which uses a facemask or mouthpiece attached to a one-way valve with a set resistance of 5 to 20 cm of water. The second device is the Flutter; another airway clearance device approved for chest therapy. The Flutter is a small handheld device that resembles a covered pipe. The bowl of the pipe contains a steel ball, which during expiration (exhaling), produces oscillations of variable breathing resistance. The third option is a high-frequency chest compression, which uses an inflatable vest driven by a pulsed-air delivery system.

Digestive problems

The digestive problems in CF can be managed by eating a well-balanced, high-caloric diet that is low in fat and high in protein. Pancreatic enzyme and vitamin A, D, E and K supplements are often prescribed to ensure good nutrition.

Liver and Gallbladder Disease

The treatment of liver disease associated with CF is oral dissolution therapy. Oral dissolution therapy consists of taking ursodeoxycholic acid (Actigall) to dissolve formations in the liver.

The treatment for gallbladder disease associated with CF is laparoscopic cholecystectomy. Laparoscopic cholecystectomy involves removing the gallbladder through a tiny incision in the navel.

Infertility

About 90 percent of all men with CF are infertile. Options for infertile men are currently limited to artificial insemination of the partner with donor sperm or adoption.

Women with CF can become pregnant via natural means or intrauterine insemination with their partner's sperm. However, pregnancy may impose a life-threatening burden on a pregnant woman with CF who has severe lung impairment.

If the patient doesn't respond to any of the treatment methods mentioned, and has severely reduced lung function and declining health, the doctor may recommend lung transplantation, the only definitive treatment for cystic fibrosis. The three-year survival rate following transplantation is about 55 percent.

Future Studies

Gene therapy to transfer the cystic fibrosis CFTR gene to the airway epithelial cells using both viral and non-viral vectors is under investigation since 1990. Gene therapy research is ongoing to develop delivery methods to carry healthy genes to the damaged cells; protein repair and drug therapy research is also underway.