Cystic fibrosis (CF) is a genetic disease that affects the body’s exocrine
glands, causing them to secrete an excess of mucus and other secretions.
Exocrine glands are responsible for secreting substances onto body surfaces both
internally (such as in the lungs) and externally (such as on the skin). Examples
of these secretions include sweat, tears, digestive juices and mucus.
Every year, 1,000 children with CF are born in the United States. CF affects
one in 3,000 Caucasian babies, making CF one of the most common genetic diseases
among Caucasians. Among African-Americans, the risk is much lower (one in
13,000) and among Asian Americans, the disease is very rare (one in 50,000). CF
affects males and females equally.
Overall, there are 30,000 Americans with CF, and an estimated 8 million
people carry one copy of the defective gene that causes the disease. These
carriers do not have symptoms of CF, because a person must inherit two defective
gene copies, one from each parent, to develop the disease. However, each child
of two CF carriers has a one in four chance of being born with CF. Genetic
testing is now available to identify couples at risk for having children with
CF.
Symptoms of CF
Normal mucus forms a gel-like barrier that plays an important role in
protecting the cells lining the inside surfaces of these tissues. In the lungs,
mucus also transports dust and other particles out of the airways and helps to
prevent infection. For patients with CF, the chemical properties of mucus become
altered; instead of protecting tissues from harm, the abnormal mucus obstructs
the ducts and airways, causing tissue damage.
The most characteristic symptom of CF is the excessive production of thick,
sticky mucus in the airways. Several factors may contribute to this mucus
abnormality. In CF, the cells lining the airways do not transport salt and water
normally, so mucus and other airway secretions may be depleted of water, thus
becoming abnormally thick.
There are also chemical changes in the mucus proteins. The mucus becomes so
thick that it clogs the airways and provides an environment in which bacteria
thrive. In response, white blood cells are recruited into the lungs to fight the
infection. These white blood cells die and release their genetic material,
sticky DNA, into the mucus. This DNA aggravates the already excessive stickiness
of the mucus, setting up a cycle of further airway obstruction, inflammation and
infection. To dislodge the mucus, CF patients cough frequently and require
time-consuming daily chest and back clapping and body positioning to drain lung
secretions.
Because the mucus provides an ideal breeding ground for many microorganisms,
CF patients have frequent airway infections. Typically, CF patients have a
pattern of low-grade, persistent infection with periodic worsening, sometimes
requiring hospitalization. These infections and the inflammation that
accompanies them gradually damage the lungs, causing respiratory failure, the
leading cause of death among CF patients.
As in the lungs, thick secretions may also clog the pancreatic ducts and
damage the pancreas. In some CF patients, this damage occurs even before birth,
while in others it develops more gradually. The pancreas supplies digestive
enzymes and bicarbonate to neutralize stomach acid so the enzymes can work
properly in the intestines. Most CF patients have insufficient amounts of
digestive enzymes for normal digestion. Pancreatic insufficiency causes
foul-smelling, bulky bowel movements, malnutrition and slowed growth and
development. Replacement of pancreatic enzymes, however, can alleviate these
symptoms. Attention to diet and supplements of fat-soluble vitamins are also
required. As the disease progresses, the cells in the pancreas that make insulin
may also be damaged causing the patient to develop diabetes.
In addition to the pancreas, abnormalities are seen in other parts of the
gastrointestinal tract in CF. The bile ducts in the liver may be affected,
causing biliary cirrhosis in a small percentage of patients. Newborns with CF
may develop a condition called meconium ileus, in which the small intestine is
obstructed by a plug of meconium, the material found in the newborn
gastrointestinal tract.
CF also affects the reproductive organs, causing infertility in nearly all
men and some women with the disease. Men with CF are generally infertile because
the tubules, called the vas deferens, that transport sperm from the testes are
absent or undeveloped. Fertility may be reduced in women due to abnormal
cervical mucus or to menstrual irregularity.
Salt absorption in the sweat ducts is also impaired and CF patients produce
sweat with five times the normal salt concentration.
The symptoms and severity of CF vary from patient to patient. For example,
not all CF patients suffer from impaired pancreatic function. The degree of lung
disease also varies. Some of this variation is due to differences in the
specific genetic defects, but even patients with identical mutations can
experience very different severities of the disease. In fact, even siblings with
the same genetic defect who share other genetic traits can have different
degrees of CF.
Causes of CF
In 1989, the genetic defect responsible for CF was discovered. Mutations in
one gene, called the cystic fibrosis transmembrane conductance regulator (CFTR),
cause the body to make nonfunctional CFTR protein, which leads to the disease.
About 500 different mutations have since been identified in CF patients all over
the world. Scientists are studying the function of the normal and the defective
CFTR proteins to understand the consequences of this defect and to develop new
treatment approaches based on that knowledge.
Diagnosing CF
After analyzing a patient’s family history and symptoms and performing a
physical examination, there are certain tests the doctor may order if CF is
suspected.
The first test that may be ordered is a sweat test. A sweat test is a
standard test in diagnosing CF. It measures the amount of salt in a patient’s
perspiration. Usually two tests will be performed in order to verify a CF
diagnosis. Newborn babies, however, are too small to produce enough sweat for
this test, so the doctor may order a blood test called an immunoreactive
trypsinogen test. Immunoreactive trypsinogen is a digestive enzyme which, if
measured in high levels, will indicate CF. A genetic test can also be performed
to confirm the presence of CF genes. It cannot, however, determine the severity
of the symptoms.
Treating and managing CF
Improvements in antibiotic therapy, clearance of lung secretions,
nutritional support, and the increase in centers with specialized expert care
have increased the average survival of patients with CF from under 5 years to
approximately 38 years.
Since the identification of the CF gene, there has been a rapid increase in
our understanding of the disease. However, until a cure is found, the pulmonary
infection and inflammation that ultimately leads to respiratory failure and
premature death remain prime targets for therapy. Continued improvement in
therapy directed toward removing airway mucus and reducing infection and
inflammation can preserve lung function until more definitive therapy is
developed. Some of the devices and drugs that have become available for therapy
include the following:
The Oscillating Device
An oscillating device, sometimes called a flutter valve, a small,
hand-held device that allows patients to loosen the mucus that clogs their
airways without having to endure conventional chest- and back-clapping therapy.
When patients exhale through the device, rapid air pressure fluctuates in the
patients' airways. The resulting vibrations dislodge the mucus from the airway
walls and promote mucus movement.
In one study, three times more mucus was cleared with an oscillating device
than after the chest clapping and vibration by an experienced respiratory
therapist, or by vigorous voluntary coughing. Treatment with this device does
not require the assistance of another person, giving the patient more
independence. Further study is still needed to determine whether the improved
airway clearance delays the onset of serious lung disease.
DNase
One factor contributing to mucus "stickiness" or
thickness, is the DNA released from white blood cells that die while fighting
bacterial infections. A naturally occurring enzyme called DNase can cut long DNA
molecules into shorter pieces and reduce their stickiness. In 1993, the Food and
Drug Administration approved the use of DNase for CF treatment. The enzyme is
administered as an aerosol spray and is generally well tolerated, although
patients may experience temporary throat irritation or hoarseness. Treatment
with DNase reduced the frequency of severe episodes of lung infection and
slightly improved lung function after 24 weeks of therapy. Longer studies are
needed to determine whether the small improvement in lung function seen at 24
weeks persists and whether this therapy will retard progressive loss of lung function.
Antibiotic Therapy of Bacterial Infection
Pseudomonas bacteria are a leading cause of lung infection and death among CF patients.
Until recently, pseudomonas infections were treated by intravenous (through the vein)
administration of antibiotics that were not available in oral form. This
treatment required high antibiotic doses so that enough of the drug would reach
the lung. Besides being expensive, the high doses could damage the patient’s
hearing and kidney function. Recently though, aerosol forms of some antibiotics
have been developed, allowing the inhaled drug to directly reach the infected
lung tissue. Inhaling the medication is not only easier and less expensive to
administer, but the required dosage is reduced, as is the potential for side effects.
Ibuprofen
Ibuprofen, an ingredient in many over-the-counter pain
relievers, has been shown to help preserve lung function in CF. This treatment
was most effective in younger patients under age 13. Ibuprofen treatment should
be performed only under medical supervision because the high drug doses required
must be determined individually for each patient.
Nutrition
Malnutrition can contribute significantly to the
deterioration of CF patients' health. Although the vast majority of CF patients
now take supplements of pancreatic enzymes to make up for poor pancreatic
function, these supplements do not fully correct the malabsorption, and many
children with CF are underweight and shorter than would be expected based on
parental height.
In recent years, increased attention to caloric needs, a balanced diet, and
supplements of vitamins and other nutrients have contributed to the increasing
longevity and well-being of CF patients. Appropriate nutritional therapy
improves the patients' growth and development, strength and exercise tolerance,
and may improve resistance to bacterial infections. However, researchers do not
yet know to what extent better nutrition can actually delay progression of lung
disease.
Lung Transplantation
It is not uncommon for CF patients, with advanced disease, to undergo double
lung transplantation.
Prognosis for CF
CF researchers from many biological and medical disciplines have made
substantial progress in developing new treatments to increase CF patients' life
expectancy and quality of life. Improved treatment of infection, airway
clearance and nutritional therapy has already had a dramatic effect on the lives
of people with CF. Parents can expect most babies born with CF to survive well
into adulthood and to lead productive and fulfilling lives.
Like many other medical conditions, education about CF and local support
groups can be the greatest tools for managing the disease and preventing
complications. The following organizations can provide additional information
about CF:
Cystic Fibrosis Foundation
6931 Arlington Road
Bethesda, Maryland 20814
(800) FIGHT CF (344-4823)
www.cff.org
National Heart, Lung and Blood Institute
P.O. Box 30105
Bethesda, MD 208524-0105
(301) 592-8573
www.nhlbi.nih.gov
© Copyright 1995-2009 The Cleveland Clinic Foundation. All rights reserved.
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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 6/11/2008...#9358
