$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 (216) 844-3237 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 (301) 496-4236 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 (203) 746-6518 Cystic Fibrosis Foundation 6931 Arlington Road Bethesda, MD 20814 International Cystic Fibrosis (Muscoviscidosis) Association 3567 East 49th Street Cleveland Ohio, 44105 (216) 271-1100) National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 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 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 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.