FREE ESSAY ON CYSTIC FIBROSIS

CYSTIC FIBROSIS

Cystic Fibrosis
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.
Bibliography
References
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.
Ramsey, B. W. Intermittent administration of aerosols in patients with cystic fibrosis.
New England Journal of Medicine. 1999; 340: 23-30.
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.