Cystic Fibrosis

Most of the symptoms of CF are related to the sticky mucus that clogs the lungs and pancreas. People with CF have difficulty breathing and are highly susceptible to bacterial infections of the lungs. Normally, bacteria are expelled from the lungs by coughing and the movement of mucus up the airways to the throat where the bacteria can be expelled. In people with CF, the mucus is too thick to be removed and bacteria are able to inhabit the lungs and cause infection.

In addition to the airways, other tissues are affected in CF. The abnormalities found in these tissues are characterized by abnormally thick and dehydrated secretions, which appear to cause obstruction resulting in organ dysfunction. For example, the pancreatic ducts are obstructed resulting in tissue degeneration, fibrosis (scarring), and organ dysfunction. The pancreas secretes enzymes during digestion that break food into smaller pieces so that the body can absorb nutrients. Enzymes speed up chemical reactions and the enzymes in the pancreas are important for digestion of foods. Failure of the pancreas to function normally results in pancreatic enzyme insufficiency, which is observed in approximately 85% of CF patients. Without treatment, enzyme deficiency results in protein and fats being poorly digested, which can lead to severe malnutrition.

In the gastrointestinal tract (the organ that digests and processes broken down food), accumulation of mucous secretions also occur. Dehydrated intestinal contents combined with abnormal mucous secretions are thought to predispose patients to bowel obstruction, which is a characteristic symptom in 10–20% of CF newborns. The bile ducts of CF patients can also be obstructed, producing gall bladder disease and elevations in liver function enzymes, occasionally leading to liver failure.

Greater than 95% of males with CF are infertile due to structural alterations in the reproductive tract that results in the sperm being incapable of fertilization, or azoospermia. These structures include the vas deferens and seminal vesicles, which are both an important part of the male reproductive tract and contribute to transportation of the sperm. If the vas deferens is absent at birth, it is a condition called congenital bilateral absence of the vas deferens (CBAVD). CBAVD is characteristic in male CF patients. Reduced fertility has also been noted in females with CF and may be related in part to abnormal mucous composition in their reproductive tract.

In the sweat gland, a characteristically detectable salty sweat represents the traditional gold standard test for diagnosing CF. Testing for CF involves analyzing sweat for elevated levels of salt. The ducts of the sweat glands normally function to reabsorb sodium and chloride across the water impermeable tissues. In CF, failure to reabsorb chloride ions in the ducts results in sodium and chloride, or salts, to be concentrated in sweat. Clinical manifestations include a predisposition to dehydration.

Despite the multi-organ involvement of the disease, respiratory failure is the primary cause of death in more than 90% of CF patients. Current hypotheses suggest that, in the CF airways, defective electrolyte transport results in alterations in the volume of liquid that covers the airways, the salt content, and/or mucus composition, which leads to thick mucus secretions that cannot be easily cleared out of the airways. The resulting airway microenvironment is conducive to chronic bacterial colonization and infection by specific bacterial pathogens, including Streptococcus pneumoniae, Hemophilus pneumoniae, and Staphylococcus aeureus. These bacteria typically infect the lungs of CF children. Adults are most susceptible to Pseudomonas aeurginosa. A rare type of bacteria called Pseudomonas cepacia currently infects people with CF at alarming rates. Pseudomonas cepacia causes a severe infection and hastens lung damage leading to an earlier death. These infections, coupled with an abnormal inflammatory response, leads to airway destruction and death in the vast majority of CF patients.

The CF gene was identified by researchers in 1989. There are many mutations (over 1,000) that cause CF. Some of these mutations cause a less severe disease; others cause a more severe disease. However, the same gene mutation in different people will not always have the same clinical manifestations.