Cystic fibrosis is the most common lethal inherited disease, affecting about 30,000 patients worldwide. In the past decade, strides in patient management and the development of new pharmacological agents, coupled with scientific and technologic advances, have increased the mean life expectancy of CF patients to approximately 30 years of age (approximately 50% of CF patients live to the age of 30). As early as 30 years ago, the median survival age was 8 years. Chronic lung infections, which lead to declines in lung function, remain the major cause of morbidity and mortality. While several pathogens have been implicated, Pseudomonas aeruginosa—an opportunistic and virulent bacterium—has an affinity for the lung tissue of CF patients. New research efforts, focused on gene mapping as a possible mechanism to identify mutations correlating with increased bacterial virulence, may lead to new therapeutic discoveries and enhanced patient outcomes (Smith, 1999).
A pair of genes that are not working properly causes cystic fibrosis. There are more than 700 different mutations that cause cystic fibrosis; however, most cases of CF are caused by relatively few mutations. This makes it possible to screen for CF carriers. The eight most common mutations in CF chromosomes are DF508, 3 mutations in exon 11-G542X, G551D, R553X, a slice mutation 621+1G-T, and mutations in amino acids 1282, 1303, and 455. These account for about 80 to 85% of the mutations in the Caucasian population. Detection rates may vary with ethnic background. Because not all cystic fibrosis mutations are detectable, a negative result does not mean that the patient is not a carrier (Lory, 1999).
The most common mutation is referred to as the DF508 deletion. In Caucasian Americans with cystic fibrosis:
? 50% have two copies of DF508
? 40% have one copy of the deletion and one other mutation
? 10% do not have the DF508 deletion
In CF carriers of other ethnic backgrounds, the DF508 deletion is present in:
? 45% of Italians
? 30% of African Americans
? 30% of Ashkenazi Jews
The type of genetic testing used to detect the DF508 deletion and other mutations is called direct testing. Current testing readily detects up to 90% of carriers in the North European Caucasian population lining in North American and 95% of the CF carriers in the Ashkenazi Jewish population. Approximately 50% of carriers in Hispanic and African American populations are detectable (Lory, 1999).
Cystic fibrosis is an inherited disorder that affects many functions of the body: breathing, digestion, and reproduction. The lifelong illness usually gets more severe with age and can affect both males and female equally. The symptoms and severity of cystic fibrosis differ from person to person. Most patients have both respiratory and digestive problems, while others only have respiratory problems. Intelligence is not affected in people with CF.
People with cystic fibrosis have secretions that are thick and sticky rather than thin and watery. In CF the glands that produce mucus, saliva, and intestinal fluids do not work properly. Thick mucus in the lungs interferes with the removal of dust and germs and can cause breathing problems, infections, and lung damage. The traditional first line of defense against the build-up of mucus is a regime of physical therapy, which helps bring up the thick mucus using mechanical methods and coughing. This needs to be done once or more times per day, every day (Ramsey, B. W., 1999).
In addition to mechanical stimulation, there are medical treatments that are also useful in helping remove and prevent the viscous secretions. A medical breakthrough in recent years was the discovery that of the three components that make up the thick mucus (protein, bacteria, and DNA of dead white blood cells) the DNA from the WBCs are most responsible for airway destruction. The concentration of dead white blood cells is approximately 1000 times larger in people with cystic fibrosis than it is in the normal lung. The long, viscous strands of DNA from these cells are the hardest things for the body to clear away. Realization of this situation resulted in the development of Genentech’s Pulmozyme (or DNAse), the first drug made specifically to address the problems of the Cystic Fibrosis lung, and one of the first biotechnology drugs. However, one cannot expect DNAse/Pulmozyme to repair scarred tissue. The advantage is only in lowering the viscosity of the mucus and reducing future damage. There is some evidence that it works better on younger patients (Ramsey, B. W., 1999).
Thick secretions may clog the pancreatic duct and block the transfer of enzymes from the pancreas to the intestine, leading to an enzyme deficiency. These enzymes break down food and supply the body with nutrients that are necessary for proper growth. The fats and proteins pass straight through the digestive system and produce greasy, smelly bowel movements. This condition is now correctable with pancreatic enzyme supplements. These pills, which are derived from animal sources (usually pigs) contain varying quantities of lipase, protease, and amylase, which are taken with meals and allow people with Cystic Fibrosis to eat the same foods as non-affected persons. In addition to enzyme supplements, oral supplements to augment total caloric intake may be needed as a result of decreased gastric absorption (Smyth, 1995).
Cystic fibrosis also affects the reproductive organs, although it affects men and women differently. Males are usually infertile, and females may experience reduced fertility due to thick secretions in the reproductive tract. Women with cystic fibrosis can have children, although the health of the mother may limit this. Childbearing is an exhausting process and some women with CF who have decided to have children have reported that it has severely compromised their health. 98% of men with cystic fibrosis cannot bear children. Sperm is produced in the CF male, but is not correctly transported to the semen because the relevant ductwork is clogged. It may be possible to surgically extract perm from men with cystic fibrosis and in this way allow them to have children (Ramsey, B., 1999).
Most CF patients are diagnosed in childhood. Some patients with mild or unrecognized symptoms may remain undiagnosed until adolescence or young adulthood. Common symptoms include chronic coughing, wheezing, sinus infections, nasal polyps (bumps inside the nose), excessive mucus production, recurrent pneumonia, poor growth, frequent foul smelling stools, enlarged fingertips, and salty tasting skin. The diagnosis of CF is usually made when a sweat test is performed and high levels of salt are found. The sweat glands of people with cystic fibrosis release salt at about five times the concentration released by normal sweat glands. This is the basis for the sweat test. It is also the reason why people affected by CF have salty tasting skin. Genetic testing can also be used to confirm the diagnosis of CF (Ramsey, B., 1999).
There is no cure for cystic fibrosis. Aerosols are used to ease breathing, and postural drainage or chest physiotherapy helps to remove mucus from the lungs. Hospitalization may be required for a thorough clean out and/or for treatment of lung infections. Pancreatic enzymes are taken with meals to help digest food. To maintain weight, frequent and high-calorie meals and snacks are recommended (Rubinstein, 1996).
There are many different genetic mutations, which lead to many different manifestations of cystic fibrosis. Not everyone with CF will have all of the complications as outlined previously, and some may have other complications in addition to those listed. Research in the field of cystic fibrosis continues at a rapid pace.
Lory, S. Genome-based approaches for the study of Pseudomonas aeruginosa infections in cystic fibrosis. Presented at the 37th Annual Meeting of the Infectious Diseases Society of America; Philadelphia, Pa; November 18-21, 1999. Session 37: Cystic Fibrosis Symposium, S70.
Ramsey, B. State-of-the-art in cystic fibrosis therapy. Presented at the 37th Annual Meeting of the Infectious Diseases Society of America; Philadelphia, Pa; November 18-21, 1999. Session 37: Cystic Fibrosis Symposium, S71.
Rubinstein, S. Constipation and meconium ileus equivalent in patients with cystic fibrosis. Pediatrics 1996; 78:473-478.
Smith, A. Cystic fibrosis: epithelial cell determinants of microbial pathogenesis. Presented at the 37th Annual Meeting of the Infectious Diseases Society of America; Philadelphia, Pa: November 18-21, 1999. Session 37: Cystic Fibrosis Symposium, S69.
Smyth, R. L. Fibrosing colonopathy in cystic fibrosis: results of case control study. Lancet 1995; 346: 1247-1251.