systic fibrosis
Cystic fibrosis (CF) is a chronic, progressive, and
frequently fatal genetic (inherited) disease of the body's mucus glands. CF
primarily affects the respiratory and digestive systems in children and young
adults. The sweat glands and the reproductive system are also usually involved.
On the average, individuals with CF have a lifespan of approximately 30 years.
CF-like disease has been known for over two centuries. The name, cystic
fibrosis of the pancreas, was first applied to the disease in 1938.
According to the data collected by the Cystic Fibrosis
Foundation, there are about 30,000 Americans, 3,000 Canadians, and 20,000
Europeans with CF. The disease occurs mostly in whites whose ancestors came from
northern Europe, although it affects all races and ethnic groups. Accordingly,
it is less common in African Americans, Native Americans, and Asian Americans.
Approximately 2,500 babies are born with CF each year in the United States.
Also, about 1 in every 20 Americans is an unaffected carrier of an abnormal "CF
gene." These 12 million people are usually unaware that they are carriers.
CF does not follow the same pattern in all patients but
affects different people in different ways and to varying degrees. However, the
basic problem is the same-an abnormality in the glands, which produce or secrete
sweat and mucus. Sweat cools the body; mucus lubricates the respiratory,
digestive, and reproductive systems, and prevents tissues from drying out,
protecting them from infection.
People with CF lose excessive amounts of salt when they sweat. This can upset
the balance of minerals in the blood, which may cause abnormal heart rhythms.
Going into shock is also a risk.
Mucus in CF patients is very thick and accumulates in the intestines and
lungs. The result is malnutrition, poor growth, frequent respiratory infections,
breathing difficulties, and eventually permanent lung damage. Lung disease is
the usual cause of death in most patients.
Cystic Fibrosis can cause various other medical problems. These include sinusitis
(inflammation of the nasal sinuses, which are cavities in the skull behind,
above, and on both sides of the nose), nasal polyps (fleshy growths inside the
nose), clubbing (rounding and enlargement of fingers and toes), pneumothorax
(rupture of lung tissue and trapping of air between the lung and the chest
wall), hemoptysis (coughing of blood), cor pulmonale (enlargement of the right
side of the heart), abdominal pain and discomfort, gassiness (too much gas in
the intestine), and rectal prolapse (protrusion of the rectum through the anus).
Liver disease, diabetes, inflammation of the pancreas, and gallstones also occur
in some people with CF.
Cystic Fibrosis symptoms vary from child to child. A baby born with
the cystic fibrosis genes usually has symptoms of cystic fibrosis during its first year. Sometimes, however,
signs of the disease may not show up until adolescence or even later. Infants or
young children should be tested for CF if they have persistent diarrhea, bulky
foul-smelling and greasy stools, frequent wheezing or pneumonia, a chronic cough
with thick mucus, salty-tasting skin, or poor growth. CF should be suspected in
babies born with an intestinal blockage called meconium ileus.
The
most common test for cystic fibrosis is called the sweat test. It measures the amount of salt
(sodium chloride) in the sweat. In this test, an area of the skin (usually the
forearm) is made to sweat by using a chemical called pilocarpine and applying a
mild electric current. To collect the sweat, the area is covered with a gauze
pad or filter paper and wrapped in plastic. After 30 to 40 minutes, the plastic
is removed, and the sweat collected in the pad or paper is analyzed. Higher than
normal amounts of sodium and chloride suggest that the person has cystic
fibrosis.
The sweat test may not work well in newborns because they do not produce
enough sweat. In that case, another type of test, such as the immunoreactive
trypsinogen test (IRT), may be used. In the IRT test, blood drawn 2 to 3 days
after birth is analyzed for a specific protein called trypsinogen. Positive IRT
tests must be confirmed by sweat and other tests.
Also, a small percentage of people with cystic fibrosis have normal sweat chloride levels.
They can only be diagnosed by chemical tests for the presence of the mutated
gene. Some of the other tests that can assist in the diagnosis of cystic fibrosis are chest
x-rays, lung function tests, and sputum (phlegm) cultures. Stool examinations
can help identify the digestive abnormalities that are typical of CF.
Genes are the basic units of heredity. They are located on
structures within the cell nucleus called chromosomes. The function of most
genes is to instruct the cells to make particular proteins, most of which have
important life-sustaining roles.
Every human being has 46 chromosomes, 23 inherited from each parent. Because
each of the 23 pairs of chromosomes contains a complete set of genes, every
individual has two sets (one from each parent) of genes for each function. In
some individuals, the basic building blocks of a gene (called base pairs) are
altered (mutated). A mutation can cause the body to make a defective protein or
no protein at all. The result is a loss of some essential biological function
and that leads to disease. Children may inherit altered genes from one or both
parents.
Diseases such as cystic fibrosis that are caused by inherited genes are called genetic
diseases. In CF, each parent carries one abnormal cystic fibrosis gene and one normal CF gene
but shows no evidence of the disease because the normal cystic fibrosis gene dominates or
"recesses" the abnormal CF gene. To have CF, a child must inherit two abnormal
genes-one from each parent. The recessive CF gene can occur in both boys and
girls because it is located on non-sex-linked chromosomes called autosomal
chromosomes. CF is therefore called an autosomal recessive genetic disease.
The inheritance patterns for the cystic fibrosis gene are shown in the accompanying
diagram. Each child, whether male or female, has a 25 percent risk of inheriting
a defective gene from each parent and of having CF. A child born to two CF
patients (an unlikely event) would be at a 100 percent risk of developing CF.
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| The presence of two mutant genes (g) is needed for CF to appear.
Each parent carries one defective gene (g) and one normal gene (G).
The single normal gene is sufficient for normal function of the
mucus glands, and the parents are therefore CF-free. Each child has
a 25 percent risk of inheriting two defective genes and getting CF,
a 25 percent chance of inheriting two normal genes, and a 50 percent
chance of being an unaffected carrier like the
parents. | |
Since CF
is a genetic disease, the only way to prevent or cure it would be with gene
therapy at an early age. Ideally, gene therapy could repair or replace the
defective gene. Another option for treatment would be to give a person with CF
the active form of the protein product that is scarce or missing.
At present, neither gene therapy nor any other kind of treatment exists for
the basic causes of cystic fibrosis, although several drug-based approaches are being
investigated. In the meantime, the best that doctors can do is to ease the
symptoms of cystic fibrosis or slow the progress of the disease so the patient's quality of
life is improved. This is achieved by antibiotic therapy combined with
treatments to clear the thick mucus from the lungs. The therapy is tailored to
the needs of each patient. For patients whose disease is very advanced, lung
transplantation may be an option.
CF was once always fatal in childhood. Better treatment methods developed
over the past 20 years have increased the average lifespan of CF patients to
nearly 30 years. These treatment approaches are detailed more fully below:
- Management of lung problems
- A major focus of cystic fibrosis treatment is the obstructed breathing that causes
frequent lung infections. Physical therapy, exercise, and medications are
used to reduce the mucus blockage of the lung's airways.
- Chest therapy consists of bronchial, or postural, drainage, which is
done by placing the patient in a position that allows drainage of the mucus
from the lungs. At the same time, the chest or back is clapped (percussed)
and vibrated to dislodge the mucus and help it move out of the airways. This
process is repeated over different parts of the chest and back to loosen the
mucus in different areas of each lung. This procedure has to be done for
children by family members but older patients can learn to do it by
themselves. Mechanical aids that help chest physical therapy are available
commercially. Exercise also helps to loosen the mucus, stimulate coughing to
clear the mucus, and improve the patient's overall physical condition.
- Medications used to help breathing are often aerosolized (misted) and
can be inhaled. These medicines include bronchodilators (which widen the
breathing tubes), mucolytics (which thin the mucus), and decongestants
(which reduce swelling of the membranes of the breathing tubes). A recent
advance, approved by the Food and Drug Administration, is an inhaled
aerosolized enzyme that thins the mucus by digesting the cellular material
trapped in it. Antibiotics to fight lung infections also are used and may be
taken orally or in aerosol form, or by injection into a vein.
- Management of digestive problems
- The digestive problems in CF are less serious and more easily managed
than those in the lungs. A well-balanced, high-caloric diet, low in fat and
high in protein, and pancreatic enzymes (which help digestion) are often
prescribed. Supplements of vitamins A, D, E, and K are given to ensure good
nutrition. Enemas and mucolytic agents are used to treat intestinal
obstructions.
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- The cystic fibrosis gene was identified in 1989. Since then, a great deal
has been learned about this gene and its protein product. The
biochemical abnormality in CF results from a mutation in a gene
that produces a protein responsible for the movement through the
cell membranes of chloride ions (a component of sodium chloride,
or common table salt). The protein is called CFTR--cystic fibrosis
transmembrane regulator.
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- CFTR is present in cells that line the passageways of the
lungs, pancreas, colon, and genitourinary tract. When this protein
is abnormal, two of the hallmarks of CF result-blockage of the
movement of chloride ions and water in the lung and other cells
and secretion of abnormal mucus.
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- The mutation involved in cystic fibrosis causes the deletion of three of
the base pairs in the gene. This in turn, causes a loss in the
CFTR protein of an amino acid (the building blocks of proteins).
Because phenylalanine is located in position 508 of the protein
chain, this mutant protein is called deltaF508 CFTR.
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- However, deltaF508 CFTR accounts for only 70-80 percent of all
CF cases. Various other mutations-over 400 at the last count-seem
to be the remaining causes of Cystic Fibrosis cases. Differences in
disease patterns seen in individuals and families probably result
from the combined effects of the particular mutation and various,
but still unknown, factors in the CF patient and his or her
environment.
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Gene therapy for cystic fibrosis is not yet possible but impressive
progress is being made in developing ways to treat the gene abnormality that
causes cystic fibrosis. In the laboratory, scientists have been able to grow cells from the
nasal passages of CF patients. By introducing the normal gene into these cells,
researchers corrected the cells' chloride transport abnormality. The chloride
defect has also been corrected in small regions in the nasal passages themselves
by giving CF patients the normal gene in nose drops.
Scientists are still looking for answers to many questions about gene
therapy. Some of these questions are: How should the gene be packaged? What are
the best ways to get the gene-containing package into the patient's lungs? What
will the long-term results of this treatment be? Can the abnormal chloride
transport be corrected in other parts of the body? How long will the correction
last? And, most importantly, can gene therapy cure or prevent the lung disease
in CF?
Finding out whether a baby is likely to have CF is possible
using prenatal genetic tests. However, the tests cannot detect all of the cystic fibrosis
gene mutations. Also, because these tests are very expensive and have certain
risks to the mother, they are not used for all pregnant women. If there is
another child with CF in the family, the expectant mother may request a prenatal
test to see if the fetus has CF genes from both parents, is a carrier for one
gene, or is altogether free of the cystic fibrosis genes.
There are two special prenatal tests that can be done--either an
amniocentesis or chorionic villus biopsy will be performed. In amniocentesis,
cells from the fluid surrounding the baby in the mother's womb (called the
amniotic fluid) are tested to see if the CF genes common to the parents are
present. In chorionic villus biopsy, cells from the tissue that will eventually
form the placenta are tested for the cystic fibrosis gene.
At
this time, preventing cystic fibrosis is not possible. In babies with two abnormal CF genes,
the disease is already present at birth in some organs, such as the pancreas and
liver, but develops only after birth in the lungs. Someday, gene therapy may be
used to prevent the lung disease from developing.
Yet, CF might be prevented in the future. Since CF occurs only when both
parents pass on a CF gene to a child, it could be prevented by identifying all
carriers of CF genes. Genetic counselors might then persuade couples who are
carriers not to have children. However, as noted, current tests can detect only
some of the more than 400 gene mutations and so the tests are only 80-85 percent
accurate.
Yet, progress in gene therapy and the realization that not all CF mutations
are life-threatening should reassure couples. Potential parents who carry the
defective gene may choose to have children.
CF education helps patients
and their families face the physical and emotional effects of the disease and
encourages CF patients to lead active, fulfilling lives. Educational programs
and materials suitable for both patients of various ages and their parents are
available from local CF centers and from local chapters of the Cystic Fibrosis Foundation.
Patients and their families and friends should know that:
- CF parents should not feel guilty or responsible for causing their child's
disease; they could not have prevented it.
- Parents should treat their children with CF as normally as possible. They
shouldn't be over-protective but should encourage them to be active and
self-reliant.
- Family and friends should remember that CF is not contagious; nobody can
get it from a patient.
- In families with CF, brothers, sisters, and first cousins of the CF
patient should be tested to see if they carry a defective gene, especially if
they seem to have a chronic lung or digestive problem. Carriers of the
abnormal gene should get genetic counseling.
- Individuals with CF have normal sexual development and can expect to have
a normal sex life. However, most, but not all, men are infertile because of a
mechanical blockage of sperm and cannot have children. Women with CF can have
children, although they may be less fertile than women without CF.
- Patients and families should work closely with doctors and other medical
specialists to develop self-management skills that can improve their quality
of life.
Above all, CF patients and their families should keep a
positive attitude. Scientists continue to make significant advances in
understanding the genetic and physiological disturbances in CF and in developing
new treatment approaches such as gene therapy. The outlook is bright for further
improvements in the care of CF patients and even for the discovery of a cure.
Keeping on Top of Your Condition
Keeping in tune with your disease or condition not only makes treatment less intimidating but also increases its chance of success, and has been shown to lower a patients risk of complications. As well, as an informed patient, you are better able to discuss your condition and treatment options with your physician.
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