Cystic fibrosis is an important genetic disease affecting both males and females of the Caucasian population; most especially those of the Northern Europe origin.
(Marieb, 2004; NHLBI, 2005) Statistics show the disease strikes one in every 3,200 babies; accounting for 5% of childhood deaths. (Marieb & Mallat, 1997; Genetics Home Reference, 2007) About 30,000 individuals in the United States have inherited the disease while about 12 million Americans are carriers of disease-causing gene. Other racial and ethnic groups are affected as well, including Latinos and Native Americans of Pueblo and Zuni.CF is less commonly observed in other racial groups wherein the disease affects 1 in every 15,000 African Americans; 1 in every 31,000 Asian Americans; and 1 in every 90,000 Asians. (Genetics Home Reference, 2007) The disease, cystic fibrosis, is suspected when the physician observes defective functioning of mucus exocrine glands throughout the body. Organ systems involved in the disease are the lungs, pancreas, liver, intestines, sinuses and sex organs. (Marieb & Mallat, 1997) Chronic respiratory infections, pancreatic enzyme insufficiency, as well as other associated complications such as infertility, occur among cystic fibrotic patients.(Sharma, 2006; Genetics Home Reference, 2007) Other names for cystic fibrosis (CF) include fibrocystic disease of the pancreas or mucoviscidosis.
(NHLBI, 2005) According to Grosse, et. al. , “after sickle cell disease, cystic fibrosis (CF) is the second most common life-shortening, childhood-onset inherited disorder in the United States”. (Grosse, Boyle, Botkin, Comeau, Kharrazi, Rosenfeld, & Wilfond, 2004) Furthermore, end-stage lung disease is the leading cause of death among these patients.(Sharma, 2006) B. Symptoms of the Disease and Effects on Human Physiology Individuals with cystic fibrosis vary in symptoms and severity of disease. Affected individuals may have serious problems at birth while some patients have milder symptoms wherein clinical manifestations appear later in their teen years or period of early adulthood. (NHLBI, 2005; Sharma, 2006) Mucus produced by exocrine glands in the various organ systems of the patient with cystic fibrosis is abnormally thick and sticky.
(Marieb & Mallat, 1997) In healthy individuals, mucus produced by various glands, acts lubricant to moisten and protect linings of respiratory airways, digestive tract, reproductive structures and other tissues. (Genetics Home Reference, 2007) Since mucus in cystic fibrosis is abnormally viscous, the substance may cause obstruction of these structures and thus, impairing function and progressively causing damage. (Marieb & Mallat, 1997; Sharma, 2006; Medline Plus, n. d.
) The physical signs that can be observed among patients with cystic fibrosis depend on the degree of involvement of various organs and disease progression.(Sharma, 2006) Respiratory System. Thick mucus obstructs the airways leading to breathing difficulties or dyspnea, chronic coughing, wheezing or crackles, respiratory distress with retractions and inflammation or various infections in the lungs such as pneumonitis or bronchitis.
Ultimately, mucus build-up and lung infections result in permanent lung damage with formation of scar tissue or lung cysts. Other signs and symptoms related to damage to respiratory system include rhinitis and nasal polyps. Cyanosis or bluish-coloration of skin and mucous membranes also reflect deficient oxygen delivery to tissues.Death is most commonly caused by respiratory failure in patients with cystic fibrosis. (Sharma, 2006; Genetics Home Reference, 2007) Gastrointestional System.
The pancreas is most commonly affected in cystic fibrosis. Insulin and pancreatic enzymes are produced in the pancreas and released into the digestive tract through the pancreatic duct. Blockage of the pancreatic duct by thickened mucus prevents release of pancreatic juices into the digestive tract. In addition, bile produced by the liver is also prevented from being releasing due to mucus blockage of bile ducts.Digestive processes are impaired in the process leading to impaired digestion and absorption of proteins, fats and fat-soluble vitamins A, D, E and K, and other nutrients resulting to malnutrition, poor growth and weight loss. Patients also experience diarrhea, steatorrhea or release of fat-laden stools. Other symptoms involving other digestive organs include abdominal distention with feelings of pain and discomfort, hepatosplenomegaly and rectal prolapse.
Some babies with cystic fibrosis have meconium ileus which is an intestinal blockage that occurs shortly after birth.(Sharma, 2006; NHLBI, 2005) Urogenital or reproductive system. Infertility in men occurs due to mucus obstruction of the vas deferens that carry sperm from the testis. Infertility may also occur, although less commonly among women with cystic fibrosis. Amenorrhea may also occur in women with severe nutritional or pulmonary involvement.
(Sharma, 2006; NHLBI, 2005) Other systems. Nonspecific physical signs of cystic fibrosis include swelling of the submandibular and parotid glands, scoliosis, kyphosis and dry skin (due to vitamin A deficiency).(Sharma, 2006) The sweat glands are also affected in cystic fibrosis wherein extremely salty perspiration is produced by these patients. Consequently, patients with CF loses large amounts of salts when they perspire, offsetting normal balance of minerals in the body.
(Marieb, 2004; Grosse, et al. , 2004) Carriers of the CF gene, however, do not manifest the disease. Nonetheless, CF carriers can pass on the abnormal gene to their offspring. (NHLBI, 2005) C. Disease Etiology and Pathogenesis The main culprit in the inherited genetic disorder, cystic fibrosis, is the defect in the CFTR gene.
(Marieb & Mallat, 1997) The cystic fibrosis transmembrane conductance regulator (CFTR) gene enodes for a protein of which functions as a chloride channel regulated by cAMP or cyclic adenosine-5′-monophosphate. This chloride channel controls the flow of chloride (Cl-) ions into and out of the cell across the cell membrane. The impairment of chloride transport results to impaired water transport across membranes as well. Note that the flow of chloride ions influences water movement within tissues and regulates the consistency of mucus.
End result of the dysfunctional process includes production of viscous mucus secretion in the respiratory, gastrointestinal, pancreatic, and other mucus exocrine glands which may cause blockage of anatomical structures by accumulated mucus; and production of extremely salty perspiration by sweat glands. (Marieb ; Mallat, 1997; Genetics Home Reference, 2007; Grosse, et al. , 2004) Cystic fibrosis is inherited as an autosomal recessive trait.
Inheriting one abnormal CFTR gene from both parents, thus, having two copies of the defective gene, predisposes an individual to the develop cystic fibrosis.(NHLBI, 2005) The gene was discovered in 1989 and recently, more than 900 mutations of the gene have been identified. (National Human Genome Research Institute, 2007) The main function of mucus production is to keep mucous linings of various organs moist and to flush out foreign debris and pathogens such as bacteria. Increased viscosity of mucus makes mucus secretions difficult to clear, thus, causing blockage and allowing bacteria, for example, to proliferate in the area. Resulting inflammation leads to various infectious disorders, for instance, respiratory infections.
(Marieb ; Mallat, 1997; NHLBI, 2005; Genetics Home Reference, 2007; Sharma, 2006) Respiratory infections are caused by a wide range of bacteria and/or viruses including Burkholderia cepacia, Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus spp. (fungus), Respiratory syncytial virus, Influenza virus and other viruses. (Saiman ; Siegel, 2004) Repeated respiratory infections may cause severe damage to the respiratory tract and later, death due to respiratory distress. (NHLBI, 2005; Genetics Home Reference, 2007; Sharma, 2006)Blockage of pancreatic ducts, by thick mucus in CF, prevents protein-digesting enzymes to be released into the small intestine. Protein digestion is impaired and malnutrition results. Release of enzymes form other digestive organs are also impaired. (Genetics Home Reference, 2007; Sharma, 2006) D. Current Therapy and Future Treatment Regimens Clinical manifestations of cystic fibrosis vary from one patient to another; therefore, therapeutic management may differ depending on clinical characteristics of the patient and health institution.
(Grosse, et al. , 2004)Patients with pancreatic insufficiency shall receive enteric-coated pancreatic enzymes and fat-soluble vitamin supplements together with food intake. These measures are taken to relieve gastrointestinal symptoms and nutritional deficiencies.
In addition, high-fat diets are prescribed to augment fat malabsorption. (Grosse, et al. , 2004; Cystic Fibrosis Foundation, 2007) Respiratory infections are treated with antibiotics, either oral, inhaled or intravenous administrations. Other conventional therapies include use of mucus-dissolving drugs or mucolytics or “clapping” the chest to loosen thick accumulated mucus and clear the airways.(Marieb, 2004; Grosse, et al. , 2004; Cystic Fibrosis Foundation, 2007) Continuous microbiologic monitoring and adequate treatment are given to prevent hospital-acquired Pseudomonas aeruginosa bacterial infection. Monoclonal antibodies have also been given to patients with CF. Other bacterial infections are managed with preparations such as recombinant DNase, inhaled tobramycin or azithromycin.
Palivizumab is a monoclonal antibody against respiratory syncytial viris or RSV to prevent infections; especially, children are at high-risk for RSV. (Grosse, et al., 2004; Cystic Fibrosis Foundation, 2007) Additionally, anti-inflammatory drugs including ibuprofen have also been useful. Antioxidants have also been used as well to benefit CF patients and prevent further damage. (Cystic Fibrosis Foundation, 2007) Ideally, therapies that will be most useful to CF patients should help improve chloride ion transport which is the main mechanism involved in the pathogenesis of cystic fibrosis. However, these therapies are still under clinical trials.
(Marieb ; Mallat, 1997; National Human Genome Research Institute, 2007) The defective gene in CF has already been isolated.In the year 1990, researchers have successfully corrected the defective gene by replacing them with normal genetic copies from cell cultures. Three years later, gene therapy was initiated with technologies that deliver the normal gene copy to the CFTR cells in the respiratory airways. The gene is carried by a common cold virus which acts as a “vector”. Other methods of gene therapy have also been studied, such as “fat capsules, synthetic vectors, nose drops or drizzling cells down a flexible tube to CFTR cells lining the airways of lungs”. (National Human Genome Research Institute, 2007)Further developments shall address treatment of other organs involved in the pathogenesis of cystic fibrosis, as soon as gene therapies for cystic fibrosis lung tissues have been found successful.
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