1. Cystic Fibrosis Board Review February 11, 2008

2. Cystic Fibrosis b Mutation in CFTR gene--epithelial chloride channels mutation causes decreased Cl transport and Na hyperabsorption leading to thick secretionsmutation causes decreased Cl transport and Na hyperabsorption leading to thick secretions most common mutation is delta-F508 (70%), however, over 1500 mutations existmost common mutation is delta-F508 (70%), however, over 1500 mutations exist b Autosomal recessive inheritance 1 in 25 to 30 Caucasians is a carrier, making disease prevalence 1 in 33001 in 25 to 30 Caucasians is a carrier, making disease prevalence 1 in 3300

3. The lungs b Major cause of death (usually by 30 years) is progressive respiratory disease. b Increased secretions lead to obstruction, leading to repeated infections (especially psuedomonas), bronchiectasis, and decline in lung function, causing respiratory failure often with a component of pulmonary hypertension and cor pulmonale

4. The pancreas b Pancreatic ducts are obstructed by thick secretions, leading to decreased excretion of enzymes into the intestine. b Pancreas is autodigested and replaced by scar tissue, resulting in decreased breakdown of fat and protein b Fat and protein malabsorption, fat-soluble vitamin deficiency

5. Fat soluble vitamins b A (retinol) blindnessblindness b D ricketsrickets b K prolonged prothrombin timeprolonged prothrombin time 2, 7, 9, 10--vitamin K dependant factors2, 7, 9, 10--vitamin K dependant factors b E (tocopherol) ptosis proprioception truncal ataxia

6. Presentation b General FTTFTT b GI meconium ileus in neonatemeconium ileus in neonate foul smelling stools, bloatingfoul smelling stools, bloating rectal prolapserectal prolapse impaction/obstructionimpaction/obstruction pancreatitispancreatitis low albumin, low sodiumlow albumin, low sodium cholelithiasis, cholecystitischolelithiasis, cholecystitis cirrhosis, portal hypertensioncirrhosis, portal hypertension neonatal hyperbilirubinemianeonatal hyperbilirubinemia fat soluble vitamin deficiencyfat soluble vitamin deficiency b Respiratory clubbing asthma COPD, barrel chest productive cough, hemoptysis nasal polyps pneumothorax/mediastinum cor pulmonale, RVH b Metabolic dehydration (low Na, low Cl) metabolic alkalosis (esp neonate) DM heat stroke b GU infertility in males

7. Diagnosis b Elevated serum trypsinogen in neonate b Gene testing 87 mutation panel (92% sensitivity)87 mutation panel (92% sensitivity) 1300 mutation panel (97 - 99% sensitivity)1300 mutation panel (97 - 99% sensitivity) b GOLD STANDARD: CHLORIDE SWEAT TEST <40 mEq/L--negative<40 mEq/L--negative 40 - 60 mEq/L--equivocal, needs repeat40 - 60 mEq/L--equivocal, needs repeat >60 mEq/L--positive, needs confirmation>60 mEq/L--positive, needs confirmation

8. Diagnosis b False positives adrenal insufficiencyadrenal insufficiency nephrogenic DInephrogenic DI hypothyroidismhypothyroidism mucopolysaccharidosi smucopolysaccharidosi s G6P deficiencyG6P deficiency hypoproteinemiahypoproteinemia anemia from poor nutritionanemia from poor nutrition b False negatives severe malnutrition with edema too little sweat inexperienced tester

9. Treatment b For acute respiratory infections: hospitalization with PCN and aminoglycoside, pulmonary toilet b baseline pulmonary therapy aerosols (bronchodilation)aerosols (bronchodilation) chest physical therapychest physical therapy aerosolized antibioticsaerosolized antibiotics systemic steroids or expectorants--not indicatedsystemic steroids or expectorants--not indicated

10. Treatment b Nutritional therapy high fat, high protein diethigh fat, high protein diet pancreatic enzyme replacementspancreatic enzyme replacements vitamin and mineral supplementsvitamin and mineral supplements b Other no support for growth hormoneno support for growth hormone pulmonary transplant--must transplant both lungs simultaneously!pulmonary transplant--must transplant both lungs simultaneously!

11. Prognosis b Life expectancy of about 32 years at best b Poorer prognosis in: femalesfemales low SESlow SES severe neonatal pulmonary diseasesevere neonatal pulmonary disease