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Cystic Fibrosis: A Genetic Disorder of the Exocrine, Digestive, and Respiratory Systemsby Brooke Holman
Cystic fibrosis is a genetic disorder affecting over 30,000 Americans, 3,000 Canadians, 20,000 Europeans and wreaks havoc on the respiratory, digestive, and exocrine systems (6). About 2,500 infants are born with CF annually in the US, and approximately 1 in every 20 Americans carries an abnormal CF gene without being aware of their carrying status (6). CF manifests itself in symptoms including: persistent coughing, excess production of sticky saliva and mucous, wheezing, shortness of breath with normal activities, abdominal pain, and weight gain (1). Sometimes infants born with CF are not diagnosed until after their first birthday, and sometimes not until adolescence or later (6). CF can also lead to an enlarged spleen and liver, diabetes, and fertility problems for men and women. Almost 95% of males with CF are sterile, and women are highly unlikely to carry a child to term due to limited lung function and other associated health risks. A mucous clogged pancreatic duct leads to the malnutrition that is associated with CF. Pancreatic enzymes are unable to reach the small intestine in order to properly metabolize food (9). This is why nutritional supplements and capsules are consumed prior to eating in order to ensure proper digestion. The disease is inherited by a mutated seventh chromosome; however both parents need to be carriers of a defected seventh chromosome in order to pass along the active disease to their children. Even at this instance, there is still only a one in four chance of having a child with CF, one in two chance of having a child who is a carrier, and a one in four chance of having a completely healthy child (1). The CF gene produces the cystic fibrosis transmembrane regulator (CFTR), which functions in the movement of chloride ions through cellular membranes. The dysfunction of the chloride channels is the basis for disease in CF (2). Malnutrition and growth retardation are common characteristics of CF patients. This is due in part to insufficient energy intake, malabsorption, and increased energy expenditure (10). CF patients suffer from a body composition that renders a depletion of lean body mass and decreased fat stores (10). Higher resting energy expenditures (REE) are responsible for the wasting body composition (10). The diagnosis for cystic fibrosis utilizes a lab test called the sweat-test (5). This test indicates an excess secretion of chloride electrolytes in the sweat. This abnormal ion transport is a primary indicator for CF. However this test is very difficult to perform and trained technicians are needed to follow very strict guidelines (5). The first step involved in this test is to place pilocarpine to a small area on the arm or leg. A copper electrode is then applied to the arm or leg and a weak electrical current is sent to stimulate sweating. The sweat is then collected in gauze or a capillary tube. Once the sweat has been collected (typically takes 30 minutes) it is ready to be analyzed for sodium and chloride concentration, conductivity or osmolarity (5). A person testing positive for CF will have sodium and chloride levels greater than 60 mmol/l (5). Treatment for CF depends on the stage of the disease and the organs involved. Mucus must be cleared from the airway by engaging in chest physiotherapy. This is where a respiratory therapist will cup their hands and strike the patient's back and chest in order to clear the airway of thick mucous. Dislodging the thick mucous prevents the chest cavity from housing bacteria which lead to respiratory track infections and pneumonia. With each meal or snack, most people with CF need to take capsules that supply the missing pancreatic enzymes and allow for proper digestion (1). In addition, treatments such as oral or inhaled antibiotics (aerosols) are taken daily to combat lung infection, corticosteroid tablets, inhaled anti-asthma therapy, vitamin A and D supplements, insulin for CF-related diabetes, and medication to relieve constipation. In combination or solo, CF patients deal with a multitude of medications and therapies day in and day out. The typical lifespan for individuals with CF is until mid-thirties; however with new technologies adolescents are expected to live until their forties (2). In the 1930's it was only expected that a child with CF would only live until their first birthday. But now patients are living into an adulthood they never thought they would see (3). Currently, the new treatments available to patients have not come from one major breakthrough, but from a multitude of minor advancements (3). Gene therapy is on the rise as a potential treatment/cure for cystic fibrosis. The goal of gene therapy is to add enough normal cells to CF airways to correct the mutated genes in order to sustain current lung function and prevent further damage (2). Gene transfer CFTR eDNA to airway epithelia has proved to be a viable way to treat this disease, but it is not that simple. Even though gene therapy would seem an obvious treatment to cystic fibrosis due to its isolated gene mutation and easy access to lung epithelial cells, numerous complexities have hindered its process. These complexities include: vector toxicity, inefficient transgene expression and limited vector production, and the constant regeneration of the epithelial cells of the respiratory tract (4). Scientists are currently working to develop more efficient delivery methods (2). Modified viruses and compacted DNA are among the vectors being tweaked to enhance the ability for successful gene transfer (2). Recently, adeno-associated virus (AAV) is being studied as an effective alternative to adenovirus gene therapy delivery systems. The AA virus is less likely to trigger the immune system and risk rejection. If a patient with CF undergoes this procedure, they are monitored to ensure that the new gene has been activated. Activation is vital to the proper functioning of ion permeability in the respiratory tract. Unfortunately this new therapy has only temporarily helped to alleviate CF complications (2). A more permanent fix to CF is still in the making, but in the mean time these types of gene transfers need to be performed on numerous occasions (2). Some of the same technology used in gene therapy is also being studied as a viable way to treat other cells of organs that are affected by CF, particularly the alpha cells of the pancreas (2). Lung transplantation is another option for treatment. Lung transplantation became an option in the 1990's with age expectancy outcomes extending into the early 30's, but the problems of organ rejection were only minimally countered with immuno-suppression therapy (8). Lung transplantation comes accompanied by a multitude of anti-rejection medications everyday and a secondary effect of decreased bone mineral density that leads to osteoporosis and osteopenia (11). Anabolic and anti-resorptive therapies have evolved to help combat the demineralizatoin of the bones (11). Exercise is used as a therapy to help reduce the mucous blockage in the lungs airway (6). This happens due to cardiorespiratory adaptations to exercise. When the human body engages in physical activity, the body adapts to the physical stressors allowing the lungs and working muscles to perform the same amount of work for less oxygen. Increasing an individual's cardio fitness level would allow that person to perform daily activities more efficiently and with less oxygen values. Since cystic fibrosis hinders the ability for the body to take in and utilize oxygen, exercise is a logical choice for treatment to decrease the levels of oxygen needed in everyday activities (7). It has also been documented that endorphins, the "feel good" hormones, are released post-exercise. Obviously any euphoric feeling will substantially benefit people with
CF. Lung function values also increase for individuals who engage in
strength or cardio exercise for one to three years (7). Strength training
also aids in increasing bone density and combating the secondary complications
of CF which can lead to osteoporosis (due in part to the malfunctions
in the digestive system). Decreased absorption of D and K fat-soluble
vitamins, altered sex hormone production, chronic inflammation, lack
of physical activity, glucocorticoid treatments, and hyper-reabsorptive
bones are responsible for bone disease within the CF population (11).
It has been known that people with mild to moderate functioning lungs
can perform the same amount of exercise as their healthy counterparts.
Most people with CF halt exercise due to muscle fatigue, and not breathlessness.
This indicates that cystic fibrosis does not affect the reserve for
exercise in the lungs, but does leave the CF population not exercising
and losing muscular endurance due to a false belief that exercise will
only exacerbate the problem (7). If individuals with CF can be educated
to exercise in order to alleviate mucous thickening, patients with cystic
fibrosis can enhance their quality of life and decrease the risk for
bacterial accumulation and subsequent respiratory infections (7). References 2) http://www.cff.org/about_cf/what_is_cf/, Assessed April 7, 2006 (link currently broken) 3) Whitford, Ben. (Sept 12, 2005)An Unexpected Reprieve; Thanks to new treatments, people with cystic fibrosis now have adulthoods they could never have imagined. In Newsweek, p64. Retrieved April 09, 2006, from Health Reference Center Academic via Thomson Gale 4) Tate, Stephen and Stuart Elborn. Progess
Towards Gene Therapy for Cystic Fibrosis. 5) Beauchamp, M and L.C. Lands. Sweat-Testing:
A Review of Current Technical 6) http://healthlink.mcw.edu/article/1031002233.html,
Assessed April 7, 2006 8) Kotloff, RM, Ahya, VN. Medical Complications of Lung Transplantation. Eur Respir J. 2004: 23, 334-342. 9) Stopka, Christine and John Todorovich. Applied
Special Physical Education and 10) Marin. Veronica et al. Energy Expenditure, Nutrition Status, and Body Composition in Children with Cystic Fibrosis. Nutrition Volume 20, No. 2, 2004. 11) Hecker TM, and RM Aris. Management of Osteoporosis
in Adults with CF. Drugs 2004; 64(2) 133-147.
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