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Cystic Fibrosis Definition
An inherited genetic disorder resulting from multiple mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) GENE on CHROMOSOME 7, inherited as autosomal recessive mutations. Researchers believe as many as 10 million people may be cystic fibrosis carriers and unaware of it. Though researchers know of approximately 600 CFTR mutations, one MUTATION, called the delta F508 mutation, accounts for about 70 percent of cystic fibrosis in the United States. About 30,000 Americans live with cystic fibrosis.
CFTR is a protein that, when functioning normally, facilitates the transport of chloride and other ions across cell membranes. In cystic fibrosis the presence of CFTR is greatly diminished and salts fail to properly cross the cell membranes. One result is very high concentrations of salts in the sweat, particularly chloride, giving the SKIN a salty taste. The effect of diminished CFTR is most pronounced on epithelial secretory cells—the cells that form mucous membranes and make up the linings of the intestinal tract, LUNGS, and urinary system, which rely on sodium chloride and other salts to draw fluid into their secretions. Without CFTR the normal watery secretions of these cells become thick and sticky.
Cystic fibrosis most seriously affects the pulmonary and gastrointestinal systems, and does so in all people who have the disorder, though the disorder involves all body systems to varying extents. Thickened secretions accumulate in the airways in the lungs, creating obstructions that interfere with BREATHING as well as establish breeding grounds for BACTERIA and other pathogens. Furthermore, the high chloride content on the surface of the epithelial cells that line the bronchial structures suppresses the body’s natural bacterial-control mechanisms. People who have cystic fibrosis have frequent or chronic upper respiratory infections and pneumonias. About 85 percent of people who have cystic fibrosis also develop pancreatic insufficiency, in which the DIGESTIVE ENZYMES the PANCREAS normally secretes do not adequately support digestion.
Symptoms of Cystic Fibrosis and Diagnostic Path
Infants who have cystic fibrosis may have MECONIUM ileus at birth, an obstruction of the bowel with meconium, a tarry substance that normally passes from the RECTUM within a few hours of birth. Other signs and symptoms of cystic fibrosis may emerge at any time and include
- large, foul-smelling, greasy-looking stools
- frequent bowel blockages
- thick SPUTUM
- coughing and wheezing
- clubbing of the fingers and toes
- INTUSSUSCEPTION (a segment of the bowel “telescopes” into another segment), a potentially life-threatening circumstance
- RECTAL PROLAPSE
- nasal polyps
Men who have cystic fibrosis nearly always have congenital bilateral absence of the vas deferens, which results in INFERTILITY, though the TESTES and other structures of the male sex organs function normally.
The diagnostic path begins with a skin salt test that measures the amount of chloride present on the surface of the skin. In cystic fibrosis these levels are five to six times normal; such a finding is generally conclusive of a diagnosis of cystic fibrosis, especially in combination with other characteristic symptoms. A BLOOD or saliva test also can confirm the presence of a cystic fibrosis mutation. Other blood tests help to assess the level of damage organ systems have experienced.
Cystic Fibrosis Treatment Options and Outlook
The most serious and common consequence of cystic fibrosis is lung damage. Doctors may prescribe ANTIBIOTIC MEDICATIONS to curtail infections, mucolytic agents and mechanical methods such as CHEST PERCUSSION AND POSTURAL DRAINAGE to help thin secretions, and bronchodilator medications to open the airways. An aerosol spray medication, dornase alpha, uses enzymes to break up secretions so the person can more easily COUGH them up. Other treatments may include pancreatic enzyme supplementation and high liquid consumption.
Cystic fibrosis is the leading reason for LUNG TRANSPLANTATION, which is a treatment that becomes necessary when the lungs can no longer function. Some people who have severe cystic fibrosis undergo simultaneous pancreas and lung transplantation. Such surgery is extensive and ORGAN TRANSPLANTATION requires lifelong IMMUNOSUPPRESSIVE THERAPY. These treatments are relatively new, so doctors do not know their long-term success. With appropriate medical management some people who have cystic fibrosis can live into at least midlife with relatively few significant complications.
Risk Factors and Preventive Measures
Cystic fibrosis is an autosomal recessive disorder acquired when each parent carries the gene mutation. Preconception GENETIC SCREENING is the only way to prevent parents from passing cystic fibrosis to their children. Because the projected number of cystic fibrosis carriers is so high (1 in 20 among Caucasians of northern European ancestry), many doctors offer cystic fibrosis screening to adults who are planning families. Though researchers hope GENE THERAPY may offer a cure for cystic fibrosis in the future, such approaches are only in the early stages of experimentation.