Cystic fibrosis

Definition
Cystic fibrosis is an inherited disorder that affects many body systems. The condition is typically characterized by chronic respiratory obstruction and infection, as well as digestive disorders. Predominantly affecting Caucasian infants, children and young adults, cystic fibrosis is the most common fatal genetic disease in the United States.

Causes/associated factors
With cystic fibrosis, a defect within the epithelial cells prevents sodium and chloride from moving in and out of cells normally. The defect causes the production of a thick, sticky mucus that plugs passages in the lungs and other organs.
Cystic fibrosis is an autosomal recessive disorder, which means an infant must receive a defective gene from both parents in order to develop the disease. One of every 31 Americans is a carrier (has the gene but not the disease) of cystic fibrosis. Each time two carriers conceive a child, the child has a 25 percent chance of developing cystic fibrosis and a 50 percent chance of becoming a carrier. The child has a 25 percent chance of not carrying the gene.

Respiratory infections are the leading cause of death for people who have cystic fibrosis. Although the median survival age is currently about 33, the rate of progressive lung disease typically determines chances of survival.


Signs/symptoms
For some people, the symptoms of cystic fibrosis are noticeable soon after birth. For others, symptoms don't appear until years later. A few people who have cystic fibrosis are not diagnosed until adulthood. About 50 percent of infants who are diagnosed with cystic fibrosis are originally diagnosed with failure to thrive, respiratory compromise or both.
The most common symptoms include dysfunction of the sweat glands, respiratory system and gastrointestinal tract.

Sweat gland symptoms
People who have cystic fibrosis often experience excessive sodium and chloride loss, especially in warm weather. This excessive loss of salt can cause an imbalance in the blood known as hypochloremic alkalosis. Children may also develop a salt "frosting" on the skin. You may notice a particularly salty taste when kissing the child.

Respiratory symptoms
Coughing is a common respiratory symptom. Often dry and irritating at first, the cough later becomes loose and productive. Some people who have cystic fibrosis develop a cough later in childhood or adolescence, but by adulthood nearly everyone who has cystic fibrosis develops a productive cough.

Other respiratory symptoms may include:

nasal polyps (growths) and sinusitis (inflammation of the sinuses)
difficulty breathing, especially for infants (Rapid breathing, coughing, wheezing and distinctive lung sounds are often heard through a stethoscope.)
recurrent bronchitis, pneumonia and other lung infections
lung obstruction, decreased airflow rate, and increased lung volume and lung size due to chronically trapped air
in advanced lung disease, a barrel chest, clubbed or squared fingers and toes, and a blue-gray cast to the skin
Gastrointestinal symptoms
Gastrointestinal symptoms occur mainly in the intestines, pancreas and liver. People who have cystic fibrosis produce mucus that often obstructs the pancreas and prevents enzymes from reaching the intestines to digest food. This leads to malabsorption of needed nutrients. As a result, people who have cystic fibrosis may have fat-soluble vitamin deficiencies, hypoalbuminemia (decreased blood albumin, one of a group of simple proteins that helps maintain blood volume and blood pressure), poor growth and decreased stores of body fat. During an episode of gastroenteritis (inflammation of the stomach and intestines), excessive sodium and chloride loss may occur. More than 85 percent of children who have cystic fibrosis have signs of maldigestion.

Other gastrointestinal symptoms may include:

frequent bulky, greasy, pale stools that typically contain visible fat droplets
increased flatulence
failure to gain weight, even with large food intake
a distended (stretched out) abdomen
decreased muscle mass with poor growth and delayed maturation
vitamin A, D, E and K deficiencies
insufficient insulin production and glucose tolerance
glycosuria (sugar in the urine)
intestinal blockage or intussusception (the slipping of one part of an intestine into another part just below)
for 15 to 20 percent of newborns, meconium ileus (a bowel obstruction that causes abdominal distention due to thick, sticky meconium stool that develops in the large intestine)
for infants and children, rectal prolapse (the dropping or falling down of the rectum) due to malnutrition and wasting of tissue near the rectum
for older children and adults, acid or bile reflux with esophagitis (heartburn with inflammation of the esophagus, the tube connecting the stomach and throat)
Other symptoms
Women who have cystic fibrosis may have amenorrhea (absence of menstruation) and cervicitis (inflammation of the cervix) with increased accumulation of mucus in the cervical canal. Women who have cystic fibrosis are typically fertile, but the stress on already damaged lungs may cause progression of lung disease during pregnancy.

More than 95 percent of men who have cystic fibrosis are sterile due to failure of the vas deferens (the tube that transports sperm) to develop or nonfunctional vas deferens due to excess mucus. Men may also have an increased rate of:

inguinal hernia (when a loop of intestine pushes through an opening in the abdominal wall into the inguinal canal, a passageway in the lower abdomen that opens into the groin)
hydrocele (a condition in which the scrotum is abnormally large due to excess fluid and poor drainage)
undescended testicles (when the testicles do not descend into the scrotal sac during childhood, which can cause infertility because testicles function at a lower body temperature and need to be in the scrotal sac to produce sperm)

Diagnosis
The sweat chloride test is the standard diagnostic tool for cystic fibrosis. A high level of chloride (salt) in the sweat generally indicates that a person has cystic fibrosis. This test is often done when:
the doctor suspects an obstructive lung disease
the person has recurrent pneumonia
the person has difficulty controlling persistent asthma
the person has confirmed pancreatic insufficiency
a child fails to thrive
a family history of cystic fibrosis exists
The following tests may be used to support a diagnosis of cystic fibrosis.

Deoxyribonucleic acid (DNA) testing can identify cystic fibrosis carriers and detect the presence of certain genetic abnormalities known to cause cystic fibrosis, such as the Delta F 508 deletion. About 70 percent of people who have cystic fibrosis have this abnormality. DNA testing may also be used as a prenatal diagnostic tool for couples who already have a child with cystic fibrosis.

Pulmonary function testing is used to measure lung capacity. By comparing the results to what is considered normal, these tests often reveal decreased lung capacity and expiration volume, as well as increased residual volume from air trapped in the lungs. Pulmonary function tests are most reliable for people age 5 or older.

Chest X-rays may indicate early signs of obstructive lung disease.

A stool specimen analysis may indicate the absence of the enzyme trypsin, which suggests pancreatic insufficiency.

Liver enzyme testing may reveal liver function abnormalities.

A sputum culture can detect organisms that people who have cystic fibrosis often have in their systems, including the bacteria staphylococcus and pseudomonas.

Measuring blood albumin levels can help determine a person's nutritional status.

An electrolyte analysis can help determine hydration status and glucose levels.

For newborns, an immunoreactive trypsin (IRT) test can screen for cystic fibrosis. A sweat test or DNA analysis is required to confirm the diagnosis. Because the long-term outcomes of early intervention are not definitive, the decision to screen newborns for cystic fibrosis is controversial.

Treatment
The goal of treatment is to help the person who has cystic fibrosis prevent loss of lung function and lead as normal a life as possible. Aggressive and early treatment of lung infections is a priority. The specific treatment for cystic fibrosis depends on the individual and the extent to which different organs are involved. A team of medical professionals may be involved in the person's care, including a doctor, pulmonologist (a doctor who specializes in the treatment of lung diseases), a gastroenterologist (a doctor who specilizes in the treatment of digestive diseases), respiratory therapist, nurse, physical therapist, registered dietitian and sometimes a psychologist.
In general, treatment involves close monitoring and early, aggressive intervention. There may be an initial hospitalization, which allows the medical team to confirm the diagnosis, assess the patient, develop and begin the treatment plan, and educate family members. Follow-up visits are often scheduled every two to three months. Sputum or throat cultures are taken at these visits to detect low-grade infections that may lead to loss of lung function. (These low-grade infections can cause changes very gradually, but without noticeable symptoms.) Most people who have cystic fibrosis also receive preventive immunizations.

Pulmonary treatment
Chest physiotherapy (PT) is done several times a day to loosen and remove lung secretions. It's important to clear these secretions to improve lung function and prevent infections. The techniques are often taught to family members so the therapy can be done at home. PT involves:

postural drainage (drainage of lung secretions by positioning the person so gravity encourages drainage)
percussion (special tapping on the chest)
breathing exercises
Various respiratory devices have been developed to assist older children and adults with chest PT. These devices can help people who have cystic fibrosis live more independently because they can be used without having to rely on someone else being present to perform the therapy. These devices include:

A mechanical inflatable vest that uses high-frequency chest compression to administer chest PT
A small, handheld, pipe-like instrument called the flutter valve that vibrates and produces a "fluttering" effect in the lungs
A machine called the intrapulmonary percussive ventilator (IPV) delivers bursts of air into the lungs through a mask
Inhaled medications, such as bronchodilators and a drug known as dornase alpha (brand name Pulmozyme), are often used in conjunction with chest PT to increase its effectiveness. Antihistamines are not recommended because they dry the mucous membranes and make it more difficult to clear mucus from the lungs. Also, expectorants do not effectively remove secretions from the respiratory tract.

Air conditioners and humidifiers can help decrease susceptibility to respiratory tract infections. Appropriate use of antibiotics can help prevent and treat infections. Aerosol solutions such as tobramycin for inhalation (TOBI) are often used to release a concentrated dose of medication directly to the infection site. Lab tests that determine the susceptibility of a bacterial infection to antibacterial drugs can help the doctor make prescription choices. Other treatments may include anti-inflammatory agents, oxygen and suctioning of the airways.

Gastrointestinal and nutritional treatment
People who have cystic fibrosis often need enriched diets. High caloric intake and high-calorie supplements or formulas are often recommended. Vitamin supplements are often recommended. Pancreatic enzyme capsules may need to be taken with each meal and snack to help the body absorb needed nutrients. When enzymes alone don't improve malabsorption, antacids may be recommended. For people who don't respond to oral supplementation, nighttime feedings through special tubes may be recommended.

Treatment plan changes
The treatment plan may be adjusted if the person experiences:

a change in cough frequency or productivity
nighttime coughing or coughing up blood
sudden cough with or without vomiting
irritability
decreased activity
decreased appetite
failure to gain weight
Treatment breakthroughs
Gene therapy, medication and protein repair therapy studies continue. A double lung transplantation may be considered for people who have severe cystitic fibrosis that doesn't respond to usual treatment.


Complications
Some people who have cystic fibrosis develop liver and/or pancreatic disease. Some people may have recurrent acute episodes of pancreatitis (an increase in pancreatic enzyme levels accompanied by abdominal pain). People who have cystic fibrosis may also develop diabetes, which can cause eye, kidney and other vascular (involving the blood vessels, veins or arteries) complications.
Vitamin E deficiencies can lead to neurological complications. Other disorders related to fat-soluble vitamin deficiencies may include:

hemolytic anemia (the destruction of red blood cells)
decreased bone density
night blindness
bleeding disorders
Nearly everyone who has cystic fibrosis eventually develops obstructive lung disease with chronic infections that lead to a loss of lung function. Initially, lung infections are often due to Staphylococcus aureus bacteria. Eventually, Pseudomonas aeruginosa bacteria may become predominant. This type of bacteria often causes a more rapid decline in respiratory function. Infection with Burkholderia cepacia bacteria can also cause a rapid decline in lung function. This type of infection may be fatal.

Other complications may include:

hemoptysis (coughing up blood)
pneumothorax (air in the chest cavity)
cor pulmonale (right-sided heart failure)
atelectasis (collapse of portions of lung due to mucus plugging)
Death is typically associated with a bout of bronchitis, pneumonia or emphysema, often related to infection and/or associated complications.


Pregnancy-specific information
Women who have cystic fibrosis often tolerate pregnancy well when lung function and nutritional status are good from the beginning. However, a moderate to severe lung condition early in the pregnancy may progress throughout the pregnancy and cause added risk.

Senior-specific information
Cystic fibrosis is rarely diagnosed in older adults.

Prevention
Cystic fibrosis cannot be prevented. If you have a positive family history of this inherited disorder, prenatal counseling is an important consideration.