CYSTIC FIBROSIS
In CF, the inherited CF gene directs the body's epithelial cells to produce a defective form of a protein called CFTR (or Cystic Fibrosis Transmembrane Conductance Regulator) found in cells that line the lungs, digestive tract, sweat glands, and genitourinary system. When the CFTR protein is defective, epithelial cells can't regulate the way chloride (part of the salt called sodium chloride) passes across cell membranes. This disrupts the essential balance of salt and water that is needed to maintain a normal thin coating of fluid and mucus inside the lungs, pancreas, and passageways in other organs. The mucus becomes thick, sticky, and hard to move.
Normally, mucus in the lungs traps germs, which are then cleared out of the lungs. But in CF, the thick, sticky mucus and the germs it has trapped remain in the lungs, and the lungs become infected.
In the pancreas, thick mucus blocks the channels that would normally carry important enzymes to the intestines to digest foods. When this happens, the child's body can't process or absorb nutrients properly, especially fats. The child has problems gaining weight, even with a normal diet and a good appetite.
A Family's Risk for CF
There are more than 1,200 different mutations of the CF gene that can lead to cystic fibrosis (some mutations cause milder symptoms than others). About 70% of people with CF have the disease because they inherited the mutant gene Delta F508 from both of their parents. This can be detected by genetic testing, which can be done in children, both before and after birth, and in adults who are thinking about starting or enlarging their families.
Of all ethnic groups, Caucasians have the highest inherited risk for CF, and Asian Americans have the lowest. In the United States today, about one of every 3,600 Caucasian children is born with CF. This compares with one of every 17,000 African Americans and only one of every 90,000 Asian Americans. Although the chances of inherited risk may vary, CF has been described in every geographic area of the world among every ethnic population.
Scientists don't know exactly why the CF gene evolved in humans, but they have some evidence to show that it helped to protect earlier generations from the bacteria that cause cholera, a severe intestinal infection.
How CF Affects Children
A few children with CF begin having symptoms at birth. Some are born with a condition called meconium ileus. Although all newborns have meconium - the thick, dark, putty-like substance that usually passes from the rectum in the first few days of a baby's life - in CF, the meconium can be too thick and sticky to pass and can completely block the intestines.
More commonly, though, babies born with CF don't gain weight as expected. They fail to thrive in spite of a normal diet and a good appetite. In these children, mucus blocks the passageways of the pancreas and prevents pancreatic digestive juices from entering the child's intestines. Without these digestive juices, the intestines can't absorb fats and proteins completely, so nutrients pass out of the body unused rather than helping the child's body grow. Poor fat absorption makes the child's stools appear oily and bulky and increases the child's risk for deficiencies of the fat-soluble vitamins (vitamins A, D, E, and K). Unabsorbed fats may also cause excessive intestinal gas, an abnormally swollen belly, and abdominal pain or discomfort.
Because CF also affects epithelial cells in the skin's sweat glands, children with CF may have a salty "frosting" on their skin or taste "salty" when their parents kiss them. They may also lose abnormally large amounts of body salt when they sweat on hot days.
Cystic fibrosis is the most common cause of pancreatic insufficiency in children, but a condition called Shwachman-Diamond Syndrome (SDS) is the second most common cause. SDS is a genetic condition that causes a reduced ability to digest food because digestive enzymes don't work properly. Some of the symptoms of SDS are similar to those of CF, so it may be confused with cystic fibrosis. However, in children with SDS, the sweat test is normal.
Because CF produces thick mucus within the respiratory tract, a child with CF may suffer from nasal congestion, sinus problems, wheezing, and asthma-like symptoms. As CF symptoms progress, the child may develop a chronic cough that produces globs of thick, heavy, discolored mucus. They may also suffer from repeated lung infections.
As chronic infections reduce lung function, the person's ability to breathe often decreases. A person with CF may eventually begin to feel short of breath, even when resting. Despite aggressive medical therapy, lung disease develops in nearly all patients with CF and is a common cause of disability and shortened life span.
Identifying a Child With CF
By performing genetic tests during pregnancy, parents can now
learn whether their unborn children may have CF. But even when genetic tests
confirm CF, there's still no way to predict beforehand whether a specific
child's CF symptoms will be severe or mild. Genetic testing can also be done on
a child after birth, and can be performed on parents, siblings, and other
relatives who are considering having a family.
After birth, the standard diagnostic test for CF is called the sweat test - an accurate, safe, and painless way to diagnose CF. In the sweat test, a small electric current is used to carry the chemical pilocarpine into the skin of the child's forearm. This stimulates sweat glands in the area to produce sweat. Over a period of 30 to 60 minutes, sweat is collected on filter paper or gauze and tested for chloride.
To diagnose CF, two sweat tests are generally performed in a lab accredited by the Cystic Fibrosis Foundation. A child must have a sweat chloride result of greater than 60 on two separate sweat tests to make the diagnosis of CF.
Several other tests serve as standard parts of the routine care used to monitor a child's CF:
Treating a Child With CF
The basic daily care program of a child with CF varies from child to child, but usually includes pulmonary therapy (treatments to maintain lung function) and nutritional therapy (a high-calorie, high-fat diet with vitamin supplements). Children with CF can also take oral doses of pancreatic enzymes to help them digest food better. They may also occasionally need oral or inhaled antibiotics to treat lung infections and mucolytic medication (a mucus-thinning drug) to keep mucus fluid and flowing.
One of the newest treatments for CF that's still being researched is an inhaled spray containing normal copies of the CF gene. These normal genes deliver the correct copy of the CF gene into the lungs of CF patients. Since 1993, more than 100 CF patients have been treated with CF gene therapy, and test trials are underway in at least nine different medical centers throughout the country and other centers around the world. Another new therapy, called protein repair therapy, aims at repairing the defective CFTR protein. Numerous medications, including a spice called curcumin, are also being tested at clinical centers across the country.
Cystic fibrosis (CF),
also called mucoviscidosis, is an autosomal recessive hereditary disease of
the exocrine glands. It affects the lungs, sweat glands and the digestive
system. It causes chronic
respiratory and digestive problems.
Contents
1 Symptoms
2 History and statistics
3 Biological causes
4 Treatment
Symptoms
The symptoms of CF usually develop during early childhood. Both lungs and
pancreas produce
abnormally viscous mucus. This mucus begins to build up and starts to clog the
opening to the
pancreas and the lungs. The mucus in the lungs can become a growth medium for
bacteria,
resulting in chronic respiratory infections and eventual permanent damage to the
lung tissue. A
chronic and loose sounding cough is common in people with CF. These thick
secretions also
obstruct the pancreas, preventing digestive enzymes from reaching the intestines
to help break
down and absorb food. Frequent and foul smelling stools are often an early sign
of CF along with
fatty oil that is visible in the stool. This can compromise growth and overall
nutrition if proper
treatment to aid digestion is not utilized early in life. As lung function
deteriorates, CF patients can
develop pulmonary hypertension and eventually cor pulmonale. Death usually
occurs from severe
infection, pneumonia, or heart failure.
The disease can be diagnosed by symptoms such as a high salt concentration in a
baby's sweat or
by genetic testing. Prior to genetic testing, a sweat test was the gold standard
for diagnosis of CF.
The disease can also be diagnosed prenatally through chorionic villi testing or
amniocentesis.
History and statistics
Cystic fibrosis (CF) was first described as a disease in the late 1930s. It is
the most common genetic
disease among people with European ancestry. Approximately one in every 25
people of European
descent is a carrier of one of the cystic fibrosis mutations, having one normal
gene and one CF
gene. Since cystic fibrosis is recessive, both copies of the gene have to be CF
genes to cause the
symptoms that occur in about 1 in every 2500 children. The high incidence of
this lethal gene can
be explained by the fact that CF carriers, who don't show any symptoms, enjoy
some protection
against cholera, since the extreme water loss in the intestines is prevented.
People from areas
where cholera is not a problem show a much lower incidence of CF. Genetic
counseling and
genetic testing is recommended for families who may be carriers of cystic
fibrosis.
In 1988, the first mutation for CF, ΔF508, was discovered by Francis Collins and
Lap-Chee Tsui on
the seventh chromosome of the human genome. Research has subsequently found over
1000
different mutations that may cause CF, however ΔF508 accounts for approximately
70% of CF
patients in Europe (this percentage varies regionally).
Biological causes
Cystic fibrosis is exclusively heritable as both parents must carry the
recessive genes for a child to
acquire the disease. At the genetic level, cystic fibrosis is the result of an
in-frame deletion of
three base pairs in the DNA. Cystic fibrosis results from the production of an
abnormal form of a
protein called cystic fibrosis transmembrane conductance regulator (CFTR). CFTR
functions in
transporting chloride ions across epithelial cells found in the lung and
intestinal tract. In CF
patients, CFTR does not function properly, causing accumulation of ions inside
epithelial cells.
Since water follows ions by osmosis, this results in water depletion and viscous
mucus on the
surface of alveolus. The most common CFTR protein abnormality is a mutation
termed ΔF508, which
is characterized by the deletion of the DNA basepair sequence at chromosome
location 7q31.1 that
codes for a single amino acid, phenylalanine.
Recent medical research is beginning to show that an imbalance of essential
fatty acids may play a
role in cystic fibrosis. Tissue samples from both mice, and more recently
humans, with CF show an
excess of arachidonic acid (AA) and a deficiency of docosahexaenoic acid (DHA).
Research has also
indicated that healthy individuals with one copy of the CF gene and one copy of
the normal gene
have fatty acid levels in between those of CF patients and people with no CFTR
gene mutations.
Further research is needed to show how this is linked to the CFTR gene defect
and what
implications this may have on treatment of cystic fibrosis.
The ΔF508 mutation is estimated to be up to 52,000 years old. Numerous
hypotheses have been put
forward as to why this recessive lethal mutation has persisted and spread in the
human population.
With the discovery that cholera toxin requires CFTR to function properly, it was
hypothesized that
carriers for cystic fibrosis benefited from resistance to cholera and other
diarrheas (Gabriel 1994).
Results of in vivo studies in mice and humans have not confirmed this hypothesis
(Cuthbert 1995,
Hogenauer 2000). Intact CFTR has also been found to be essential for the entry
of Salmonella typhi
into cells (Pier 1998), suggesting that carriers for cystic fibrosis might be
resistant to typhoid fever.
No in vivo study has yet confirmed this. In both cases, the low level of cystic
fibrosis outside of
Europe, in places where both cholera and typhoid fever are endemic, is not
immediately explicable.
Treatment
A typical breathing treatment for Cystic Fibrosis, using a nebulizer and the
ThAIRapy VestDaily chest
physiotherapy and aerosol breathing treatments are very commonly prescribed for
CF treatment.
Typical physical therapy involves manual chest percussion (pounding), positive
pressure
techniques and/devices or possibly using a device such as the ThAIRapy Vest or
the
Intrapulmonary Percussive Ventilator (IPV) to achieve the same effect: loosening
of the thick
mucus. Aerosolized medicines commonly given include albuterol, ipratropium
bromide and
Pulmozyme to loosen secretions and decrease inflammation. It was found that CF
sufferers that
surf were healthier; consequently, some hospitals use a nebulised 6%-8% Saline
solution on those
CFs that do not have asthma to loosen the secretions. Inhaled aminoglycoside
antibiotics are
sometimes given to fight infections.
CF patients are typically hospitalized somewhat regularly, often every 6 months
depending on the
severity of the case. Patients often have intravenous antibiotics through a PICC
line , Central Line
or chest port.
Earlier approaches to diabetes treatment among CF patients generally did not
address long-term
effects because of the short CF life expectancy. However due to improving
treatment of CF
patients and their resulting longer lifespan, it is increasingly common to
address diabetes
symptoms that are not immediately harmful. As maintaining body weight is
important for CF patients,
a typical diabetic diet is not feasible and therefore insulin doses are instead
adjusted to fit the
typical high-calorie/high-fat CF diet.
Due to advances in medical treatment, the median life expectancy of a newborn
with cystic fibrosis
increased from 4 years (in the 1960s) to 32 years today. These procedures
include the intake of
digestion enzymes, nutritional supplements, percussion and postural drainage of
the lungs,
improved antibiotics and inhalation of aerosols containing medication. A few
attempts at gene
therapy were initially successful, but failed to produce acceptable long-term
results.
Some cystic fibrosis patients go on to have a lung transplant.
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Most of us have heard of cystic fibrosis (CF),
and know that it is a life sapping disease that primarily affects children,
but there's more to it than that.
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