CD-ROM Today (UK) (Spanish) 15/CDRT.iso/dp/0364/03642.txt

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$Unique_ID{BRK03642}
$Pretitle{}
$Title{Cystic Fibrosis}
$Subject{Cystic Fibrosis Pancreatic Fibrosis Mucoviscidosis Mucosis
Fibrocystic Disease of Pancreas CF}
$Volume{}
$Log{}

Copyright (C) 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992
National Organization for Rare Disorders, Inc.

24:
Cystic Fibrosis

** IMPORTANT **
It is possible that the main title of the article (Cystic Fibrosis) is
not the name you expected.  Please check the SYNONYM listing to find the
alternate name and disorder subdivisions covered by the article.

Synonyms

     Pancreatic Fibrosis
     Mucoviscidosis
     Mucosis
     Fibrocystic Disease of Pancreas
     CF

General Description

** REMINDER **
The information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about the disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Cystic Fibrosis is an inherited disorder that affects the exocrine, or
outward-secreting, glands of the body.  It affects children and young adults.
The main consequences are related to the mucus producing glands.  The
secreted mucus is thick and sticky, clogging and obstructing air passages in
the lungs and pancreatic bile ducts.  Cystic Fibrosis also causes dysfunction
of salivary and sweat glands.  There is presently no cure for CF, but with
proper treatment, those affected can lead active lives.

Symptoms

Ten to fifteen percent of those affected manifest symptoms at birth in the
form of an intestinal blockage known as meconim ileus.  In many others,
symptoms appear during the first few months of life.  Symptoms are varied and
can be divided into three major groups.

Pulmonary (respiratory) Problems:  Most Cystic Fibrosis patients develop
lung disease.  The thick mucus obstructs the airways of the lungs and
respiratory system.  This interferes with the patient's breathing and may
cause damage of the lung tissue.  Cystic Fibrosis patients are also
susceptible to lung infections, especially those caused by Staphylococcus
Aureus and Pseudomonas Aeruginosa bacteria.  Early symptoms include a dry,
hacking, nonproductive cough, increased respiratory rate, often with
wheezing, prolonged expiratory phases of respiration and decreased activity.
Later signs include an increased cough with sputum production, rales, musical
rhonchi, scattered or localized wheezes, repeated episodes of respiratory
infection and signs of obstructive lung disease.  Other symptoms include
increased front to back measurement of the chest, diminished areas of cardiac
dullness, a depressed diaphragm, and palpable liver border.  There may also
be decreased appetite, weight loss, failure to gain weight or grow, decreased
exercise tolerance and digital clubbing.

Advanced signs of the disease:  chronic, paroxysmal, productive cough,
often associated with vomiting; increased respiratory rate, shortness of
breath on exertion, orthopnea, dyspnea; diffuse and localized rales and
rhonchi; signs of marked obstructive lung disease; marked increase in front
to back measurement - barrel chest, pigeon breast; limited respiratory
excursion of thoracic cage; depressed diaphragm; hyperresonance over entire
chest; decreased air exchange; noisy respiration - wheezing, bubbling,
audible rales; marked decrease in appetite associated with weight loss;
growth failure, stunting; muscular weakness, flabbiness; cyanosis; rounded
shoulders, forward position of head, poor posture; fever, tachycardia;
hemoptysis; atelectasis; pneumothorax; lung abscess; signs of cardiac failure
- edema, enlarged, tender liver, venous distention; visual impairment and
facial changes; bone pain and osteoarthropathy.  Upper respiratory symptoms
include nasal polyps and chronic sinusitis.

There are also gastrointestinal problems.  In Cystic Fibrosis, the thick
mucus blocks the pancreatic duct that carries digestive enzymes to the
intestines causing incomplete digestion of food.  Pancreatic and nutritional
symptoms may include:  meconimeus; intestinal obstruction; intussusception;
fecal masses; poor weight gain despite voracious appetite; easy bruising,
secondary to vitamin K deficiency; malnutrition, poor muscle tone, small
flabby muscles, lack of subcutaneous fat; and vitamin deficiencies.  There may
also be a distended abdomen, three or more bulky, greasy, floating, foul-
smelling stools per day, chronic diarrhea in infancy, rectal prolapse, cramps
and excessive foul gas, hypoproteinemia with generalized edema, pancreatitis
and diabetes.

Biliary cirrhosis and portal hypertension symptoms include:  jaundice in
new born; firm, modular liver, often palpable in midline; splenomegaly;
hypersplenism - decreased white blood count and platelets, anemia; hematemesis
and melena from esophageal varices; and ascites.

Sweat gland problems also occur - Hyponatremia and Hypochloremia.
Because of the high concentration of salt and chlorine secreted by the sweat
glands, those suffering from Cystic Fibrosis experience extreme heat
exhaustion during periods of exercise, hot weather or febrile states (fever).
They also experience dehydration during periods of exercise, hot weather or
febrile states.  In addition, severe muscle cramps, weakness and shock may
occur, or in the mild form the forehead tastes salty.

Genital track involvement symptoms may include aspermia, blockage or
absence of vas deferens cervical polyps and increased viscosity of mucus.

Approximately ninety-five percent of males with cystic fibrosis are
sterile.  Women with CF usually have reproductive problems as well.
Menstrual cycles may become irregular and vaginal infections may occur as a
side effect of antibiotic treatment of this disorder.  Although becoming
pregnant may be difficult for women with CF, they are not sterile, and can
give birth to normal children.

Patients should be tested for Cystic Fibrosis when the following
conditions are encountered:  chronic cough, bronchitis, pneumonia, pertussis;
allergy - rhinitis, sinusitis, nasal polyposis, and post nasal drip
(sometimes mistakenly attributed to allergy); aspiration, chronic cough;
asthma; nasal polyposis or chronic sinusitis; tuberculosis; pulmonary
lesions; intestinal obstruction in the newborn; failure to thrive/
malnutrition; celiac disease; malabsorption; rectal prolapse; dysautonomia,
agammaglobulinemia; cirrhosis of the liver; heat stroke; diagnosis of CF in a
sibling; or a chest x-ray that reveals irregularity of aeration with patchy
areas of atelectasis and generalized overinflation.

Causes

Cystic Fibrosis is inherited as an autosomal recessive disorder.  (Human
traits including the classic genetic diseases, are the product of the
interaction of two genes for that condition, one received from the father and
one from the mother.  In recessive disorders, the condition does not appear
unless a person inherits the same defective gene from each parent.  If one
receives one normal gene and one gene for the disease, the person will be a
carrier for the disease, but usually will show no symptoms.  The risk of
transmitting the disease to the children of a couple, both of whom are
carriers for a recessive disorder, is twenty-five percent.  Fifty percent of
their children will be carriers, but healthy as described above.  Twenty-five
percent of their children will receive both normal genes, one from each
parent and will be genetically normal.)

Recent scientific investigations indicate that a malformed protein
located in the cell membrane may be linked to cystic fibrosis.  A special
channel or gate through which chloride particles normally flow in and out of
the cell seems to involve an abnormality in the way chloride is transported
across the cell membrane in some CF patients.  The gene that causes Cystic
Fibrosis was identified in 1989, which may shed light on more specific
causes.

The thick mucus that characterizes the disease may be caused by limited
secretion of chloride (which affects water balance in the cell).  Thus water
might be held inside the cell, causing the passages to become dry.  The mucus
lining the passages may lose water and become thick.  The same defect in
cells lining the sweat glands is thought to alter the salt concentration in
the sweat of CF victims.  Another theory asserts that this defect is a
byproduct of the disease rather than the primary defect.  This theory
involves the belief that the gene produces an enzyme that changes the
chemical structure of the mucus.  This overactive enzyme may also alter the
chloride channels in sweat cell membranes, leading to production of
abnormally salty sweat.

Affected Population

There are about 33,000 cases of Cystic Fibrosis in the United States.  It
mostly affects caucasian children and young adults, although there is a small
but significant number of blacks and orientals affected.

Therapies:  Standard

There is presently no cure for Cystic Fibrosis.  Various treatments can help
patients lead normal, active lives and those affected are usually encouraged
to lead active lives.  Genetic tests are available to determine if parents
are carriers of the CF gene, and if a fetus will be affected.  However,
scientists are developing a neonatal screening test for Cystic Fibrosis.
Since early treatment may lead to better quality of life for CF patients,
this early diagnosis will be of great help to children with CF.

In the area of physical therapy, postural drainage, specifically
bronchial drainage is the most important form of preventive therapy and is
often used in conjunction with aerosol inhalation.  Postural Drainage loosens
the mucus from the lungs and helps keep the lung passages open.  This therapy
is generally carried out twice a day.  Breathing exercises help improve the
patient's respiration, ventilation and posture.

Aerosol therapy entails the inhalation of particulate water and
medication via nebulizers and is effective in wetting and thinning the mucus
secretions in the airways.

Pancreatic deficiency is treated by replacement therapy and diet.

A doctor can prescribe a diet which is high in protein, calories and
vitamins.

The prevention of infection is the best treatment of pulmonary infection
and is a good means of maintaining clear airways.

Patients should be given extra salt with their food and occasionally take
salt tablets in order to be protected from acute salt loss.  A doctor should
be consulted regarding the amount of salt needed.

Therapies:  Investigational

Research is ongoing in the treatment of Cystic Fibrosis.

The 1989 discovery of a gene that causes cystic fibrosis (CF) has
provided new impetus to the search for the underlying cause of CF.  It is
hoped that research on this gene will lead to new treatments and eventually a
cure.

Clinical trials of the Orphan Drug DNase were begun in June of 1990.
DNase is an enzyme that affects the thickness of mucus secretions.  One study
of DNase is being conducted at the National Heart, Lung, and Blood Institute
(NHLBI), the other study is underway at the University of Washington in
Seattle, WA.  DNase is manufactured by Genentech, South San Francisco, CA.

Scientists are studying an aerosol high blood pressure drug, Amiloride,
which may delay, but not prevent, lung damage in people with CF.  More
research is needed to determine the safety and effectiveness of this
treatment.

A new treatment, Secretory Leukocyte Protease Inhibitor (SLPI) is to
begin to be used in clinical trials with human patients with collaboration by
the National Heart, Lung & Blood Institute (NHLBI) and the manufacturer,
Synergen, Inc., of Colorado.  Information on the trials can be obtained from
the Cystic Fibrosis Foundation listed in the Resources section.

Univax Biologics, Inc., 12111 Parklawn Dr., Rockville, MD, 20852, has
received orphan drug designation for MEPIG, generic name Mucoid
Expolysacchride Pseudomonas Hyperimmune Globulin for the treatment of
patients with Cystic Fibrosis for the prevention of lung infections due to
Pseudomonas Aeruginosa.

Drs. T. Kennedy and J. Hoidaal, 7702 Parham Rd., Richmond, VA, 23294, are
working on an orphan drug, Dextran Sulfate (inhaled, aerosolized), trade
name, Unedex, as an adjunct to the treatment of Cystic Fibrosis.

Researchers are studying the use of aerosalized Alpha-1-Antitrypsin in CF
patients.  This drug is presently made in intravenous (IV) form by Miles
Laboratories as Prolastin.  However, the IV form does not seem to help the CF
patient.  More research is needed to determine if this drug will work when
patients breathe it directly into the lungs.

The FDA has approved the following drug for testing as a treatment for
Cystic Fibrosis patients:

The orphan drug amibride HCL solution for inhalation is being tested as a
treatment for Cystic Fibrosis patients.  The drug is manufactured by Glaxo,
Research Triangle Park, NC.

Other drugs being tested for CF include adenosine triphosphate and
uridine triphosphate.  These two drugs work on a chloride in the nasal
passages to thin sputum.

Recombinant human deoxyribonuclease is a drug that also works on thinning
of the CF patient's sputum.

The steroid prednisone is often used to control infection in CF patients;
however, many persons experience serious side effects from its use.  More
study is needed to determine the long-term safety and effectiveness of this
drug.

A look into the use of ibuprofen to reduce the infection of chronic
bronchitis that affects CF patients is also very promising.

For additional information on the treatment of Cystic Fibrosis, see
"Cystic Fibrosis:  New Treatments Give Victims Precious Time" in the
Prevalent Health Conditions/Concerns area of NORD Services.

Clinical trials are underway to study the use of 1-antitrypsin
(ProlastinR) in Cystic ibrosis.  Interested persons may wish to contact:

     Melvin Berger, M.D., Ph.D.
     Rainbow Babies and Children's Hospital
     2101 Adelbert Rd., Rm. 594
     Cleveland, OH  44106
     [phone]

to see if further patients are needed for this research.

The orphan product, Cystic Fibrosis Transmembrane Conductance Regulator,
sponsored by Genzyme Corp., Cambridge, MA, 02139, is being tested as a
protein replacement therapy in patients with Cystic Fibrosis.

Up until the end of 1991, 312 people with Cystic Fibrosis had undergone
experimental lung transplants.  Fifty-two percent of these patients survived
three years after the transplant.

Several researchers are studying gene therapy for Cystic Fibrosis by
inserting the normal CFTR gene into a virus that causes a cold (adenovirus),
and delivering the virus directly into the lung.  When the virus is modified
with the normal CFTR gene, its ability to reproduce itself is destroyed so
that it cannot cause a cold.  This research is being conducted by:

     Dr. Ronald Crystal
     NIH/National Heart, Lung & Blood Institute (NHLBI)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

     Dr. Michael J. Welsh
     Howard Hughes Medical Institute
     Dept. of Internal Medicine
     University of Iowa College of Medicine
     Iowa City, IA  52242

     Dr. James Wilson
     University of Michigan Medical Center
     Division of Meolecular Medicine and Genetics
     Ann Arbor, MI  48109-0650

This disease entry is based upon medical information available through
November 1992.  Since NORD's resources are limited, it is not possible to
keep every entry in the Rare Disease Database completely current and
accurate.  Please check with the agencies listed in the Resources section for
the most current information about this disorder.

Resources

For more information on Cystic Fibrosis, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     Cystic Fibrosis Foundation
     6931 Arlington Road
     Bethesda, MD  20814

     International Cystic Fibrosis (Muscoviscidosis) Association
     3567 East 49th Street
     Cleveland Ohio,  44105
     [phone])

     National Digestive Diseases Information Clearinghouse
     Box NDDIC
     Bethesda, MD  20892
     [phone]

     Cystic Fibrosis Research Trust
     Alexandria House
     5 Blyth Rd.
     Bromley, Kent BR1 3RS
     England

     Canadian Cystic Fibrosis Foundation
     586 Eglinton Avenue East, Suite 204
     Toronto, Ontario M4P 1P2

For information on genetics and genetic counseling referrals, please
contact:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Ave.
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

THE MERCK MANUAL 15th ed.  R. Berkow, et al:  eds; Merck, Sharp & Dohme
Research Laboratories, 1987.  Pp. 1832, 2055.

CECIL TEXTBOOK OF MEDICINE, 18th ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Eds.:  W. B. Saunders Co., 1988.  P. 1534.