Every year, 1,000 children with cystic fibrosis (CF) are born in the United States. One in 3,000 Caucasian babies have the disorder, making CF one of the most common lethal genetic diseases in Caucasians. Overall, there are 30,000 Americans with CF, and an estimated 8 million people carry one copy of the defective gene that causes the disease. These carriers do not have symptoms of CF, because a person must inherit two defective gene copies-one from each parent-to develop the disease. However, each child of two CF carriers has a one in four chance of being born with CF. Genetic testing is now available to identify couples at risk for having children with CF.
CF affects tissues that produce mucus secretions, such as the airway, the gastrointestinal tract, the ducts of the pancreas, the bile ducts of the liver and the male urogenital tract. Normal mucus forms a gel-like barrier that plays an important role in protecting the cells lining the inside surfaces of these tissues. In the lung, mucus also transports dust and other particles out of the airway and helps to prevent infection. CF alters the chemical properties of mucus; instead of protecting tissues from harm, the abnormal mucus obstructs the ducts and airways, causing tissue damage.
The most characteristic symptom of CF is the excessive production of thick, sticky mucus in the airways. Several factors may contribute to this mucus abnormality. In CF, the cells lining the airway do not transport salt and water normally, so mucus and other airway secretions may be depleted of water.
There are also chemical changes in the mucus proteins. The mucus becomes so thick that it clogs the airways and provides an environment in which bacteria thrive. In response, white blood cells are recruited into the lung to fight the infection. These white blood cells die and release their genetic material, sticky DNA, into the mucus. This DNA aggravates the already excessive stickiness of the mucus, setting up a vicious cycle of further airway obstruction, inflammation and infection. To dislodge the mucus, CF patients cough frequently and require time-consuming daily chest and back clapping and body positioning to drain lung secretions.
Because the mucus provides an ideal breeding ground for many microorganisms, CF patients have frequent airway infections. Among the most common germs causing infections in CF patients are Pseudomonas bacteria. This germ is difficult to clear in CF patients, even after treatment with antibiotics. Typically, CF patients have a pattern of low-grade, persistent infection with periodic worsening, sometimes requiring hospitalization. Recurring Pseudomonas infection and the inflammation that accompanies it gradually damage the lungs, causing respiratory failure, which is the leading cause of death among CF patients.
As in the lung, thick secretions clog the pancreatic ducts and damage the pancreas. In some CF patients, this damage occurs even before birth, while in others it develops more gradually. The pancreas supplies digestive enzymes and bicarbonate to neutralize stomach acid so the enzymes can work properly in the intestine. Most CF patients have insufficient amounts of digestive enzymes for normal digestion. Pancreatic insufficiency causes foul-smelling, bulky bowel movements, malnutrition and slowed growth and development. Replacement of pancreatic enzymes can alleviate these symptoms. Attention to diet and supplements of fat-soluble vitamins are also required. As the disease progresses, the cells in the pancreas that make insulin may also be damaged and patients may develop diabetes
In addition to the pancreas, abnormalities are seen in other parts of the gastrointestinal tract in CF. The bile ducts in the liver may be affected, causing biliary cirrhosis in a small percentage of patients. Newborns with CF may develop a condition called meconium ileus, in which the small intestine is obstructed by a plug of meconium, the material in the newborn gastrointestinal tract.
CF also affects the reproductive organs, causing infertility in nearly all men and some women with the disease. Men with CF are generally infertile because the tubules, called the vas deferens, that transport sperm from the testes are absent or undeveloped. Fertility may be reduced in women due to abnormal cervical mucus or to menstrual irregularity. Although pregnancy can be risky, many women with CF with relatively good pulmonary function have borne healthy children. However, the incidence of CF in their offspring is about one in 50.
Salt absorption in the sweat ducts is also impaired, and CF patients produce extremely salty sweat. Based on this observation, a scientist working at NIDDK forty years ago developed a sweat test to diagnose CF. This test is still the standard for diagnosis. With the discovery of the gene defective in CF, the sweat test can be supplemented by genetic tests when the results are ambiguous.
The symptoms and severity of CF vary from patient to patient. For example, not all CF patients suffer from impaired pancreatic function. The degree of lung disease also varies. Some of this variation can be attributed to differences in the specific genetic defects in different patients, but even patients with identical mutations may have very different severities of disease. Even siblings with the same genetic defect who share other genetic traits can have different CF manifestations. Therefore, although the specific mutation in the CF gene contributes to the course of the disease, other differences in the individual genetic makeup, and perhaps in the environment, also play a role.
People with cystic fibrosis usually die of respiratory failure after years of deteriorating lung function. While most patients diagnosed with the disorder die young, about 35 percent reach adulthood.
- Lung & Airway Disorders