Cystic fibrosis

Etiology and epidemiology Cystic fibrosis (CF) is an autosomal recessive disorder that is the most common life limiting genetic disease in whites. In the united states, the incidence of CF is approximately1 in 3200 whites, 1 in African American, and 1 in persons of Asian heritage. The gene for CF, located on the long arm of chromosome 7, encodes for a polypeptide, the cystic fibrosis transmembrane regulator (CFTR), a chloride channel located on the apical surface of epithelial cells.

CFTR is important for the proper movement of salt and water across cell membranes and maintaining the appropriate composition of various secretions. Especially in the airways, liver, and pancreas. The most common mutation is a deletion of three base pairs resulting in the absence of phenylalanine at 508 position. More than 1500 mutations of CFTR gene have been identified.

The secretory and absorptive characteristics of epithelial cells are affected by abnormal CFTR, resulting in the clinical manifestations of CF. The altered chloride ion conductance in the sweat gland results in excessively high sweat sodium and chloride levels. The defect in CFTR may also reduce the function of airway defenses and promote bacterial adhesion to the airway epithelium. This all leads to chronic airway infections and eventually to bronchial damage (bronchiectasis).

Clinical manifestations CF is a chronic progressive disease that can present with protein and fat malabsorption( failure to thrive, hypoalbuminemia, steatorrhea), liver disease ( cholestatic jaundice), chronic respiratory infection. The most common bacterial infection are staphylococcus aureus and pseudomonas aeruginosa.

Chronic brochial infection results in persistent or recurrent cough that is often productive of sputum. Chronic airway infections lead to airway obstruction and bronchiectasis,eventually to pulmonary insufficiency and premature deaths. The median age of survival is currently in mid 30s. Digital clubbing is common in patient with CF. chronic sinusitis and nasal polyposis are common.

Allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to aspergillus in CF airways Ninety percent of patients with CF are born with exocrine pancreatic insufficiency.this leads to malabsorption of proteins, sugars and fat. Fat malabsorption manifests clinically as steatorrhea, deficiencies of fat soluble vitamins (A,D,E and K), and failure to thrive.

Ten percent of patients with CF are born with intestinal obstruction caused by inspissated meconium(meconium ileus). In older patients intestinal obstruction may results from thick inspissated mucus in the intestinal lumen ( distal intestinal obstruction syndrome). In adolescent or adults a progressive pancreatic damage can lead insulin deficiency.

The failure of the sweat ducts to conserve sodium and chloride may lead to hyponatremia and hypochloremic metabolic alkalosis. Inspissation of mucus in the reproductive tract leads to reproductive dysfunction in both males and females. CF should be in the differential diagnosis of children with respiratory or gastrointestinal symptoms, especially if there is digital clubbing. Any child with nasal polyps, especially those younger than 12 years should be evaluated for CF.

Diagnostic studies The following criteria should met to establish diagnosis of CF: 1.two elevated sweat chloride tests (positive the value is >60mEq/L, borderline if 40to 60mEq/L, a negative if <40 mEq/L, with adequate sweat collection) 2.two mutations known to cause CF identified by DNA analysis or 3.a characteristic abnormality in ion transport across nasal epithelium (nasal potential difference testing). Identification of carriers and prenatal diagnosis of children with mutation is offered at most medical centers.

Complications of cystic fibrosis Respiratory complication ٭ Bronchiectasis, bronchitis, pneumonia Atelectasis,hemoptysis, pneumothorax, nasal polyp, sinusitis, cor epulmonale, respiratory failure.

GIT complications Meconium ileus Meconium plug syndrome Volvulus Distal intestinal obstruction syndrome Rectal prolapse Intussupception Fibrosing colonopathy

Appendicitis, pancreatitis Hepatic cirrhosis Growth failure Diabetes *Other complications Infertility Delyed puberty Electrolytes disturbance(hyponatremia, hypokalemia, hypochloremia,metabolic alkalosis )

Treatment The treatment of CF is multifactorial, but primarily directed toward the GIT and pulmonary complications. Chest physiotherapy help remove mucus from the airways, antibiotic therapy is important in controlling infections( oral, aerosolized and IV). Exocrine pancreatic insufficiency is treated with enteric coated pancreatic enzyme capsules and the patients should follow high calorie diets.

Lipase dose exceeding 2500 U/Kg/meal are contraindicated because they have been associated with fibrosing colonopathy. Fat soluble vitamins are recommended. Newborns with meconium ileus may require surgical intervention, but some can be managed with contrast( gastrografin) enemas.