Cystic FibrosisCystic Fibrosis

Board ReviewBoard Review

February 11, 2008February 11, 2008

Cystic FibrosisCystic Fibrosis

Mutation in CFTR gene--epithelial chloride Mutation in CFTR gene--epithelial chloride channelschannels• mutation causes decreased Cl transport and mutation causes decreased Cl transport and

Na hyperabsorption leading to thick Na hyperabsorption leading to thick secretionssecretions

• most common mutation is delta-F508 (70%), most common mutation is delta-F508 (70%), however, over 1500 mutations existhowever, over 1500 mutations exist

Autosomal recessive inheritanceAutosomal recessive inheritance• 1 in 25 to 30 Caucasians is a carrier, making 1 in 25 to 30 Caucasians is a carrier, making

disease prevalence 1 in 3300disease prevalence 1 in 3300

The lungsThe lungs

Major cause of death (usually by 30 Major cause of death (usually by 30 years) is progressive respiratory disease.years) is progressive respiratory disease.

Increased secretions lead to obstruction, Increased secretions lead to obstruction, leading to repeated infections (especially leading to repeated infections (especially psuedomonas), bronchiectasis, and psuedomonas), bronchiectasis, and decline in lung function, causing decline in lung function, causing respiratory failure often with a respiratory failure often with a component of pulmonary hypertension component of pulmonary hypertension and cor pulmonaleand cor pulmonale

The pancreasThe pancreas

Pancreatic ducts are obstructed by Pancreatic ducts are obstructed by thick secretions, leading to decreased thick secretions, leading to decreased excretion of enzymes into the intestine.excretion of enzymes into the intestine.

Pancreas is autodigested and replaced Pancreas is autodigested and replaced by scar tissue, resulting in decreased by scar tissue, resulting in decreased breakdown of fat and proteinbreakdown of fat and protein

Fat and protein malabsorption, fat-Fat and protein malabsorption, fat-soluble vitamin deficiencysoluble vitamin deficiency

Fat soluble vitaminsFat soluble vitamins

A (retinol)A (retinol)• blindnessblindness

DD• ricketsrickets

KK• prolonged prolonged

prothrombin timeprothrombin time• 2, 7, 9, 10--vitamin 2, 7, 9, 10--vitamin

K dependant K dependant factorsfactors

E (tocopherol)E (tocopherol)• ptosisptosis• proprioceptionproprioception• truncal ataxiatruncal ataxia

PresentationPresentation

GeneralGeneral• FTTFTT

GIGI• meconium ileus in neonatemeconium ileus in neonate• foul smelling stoolsfoul smelling stools, bloating, 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

RespiratoryRespiratory• clubbingclubbing• asthmaasthma• COPD, barrel chestCOPD, barrel chest• productive cough, hemoptysisproductive cough, hemoptysis• nasal polypsnasal polyps• pneumothorax/mediastinumpneumothorax/mediastinum• cor pulmonale, RVHcor pulmonale, RVH

MetabolicMetabolic• dehydration (low Na, low Cl)dehydration (low Na, low Cl)• metabolic alkalosis (esp neonate)metabolic alkalosis (esp neonate)• DMDM• heat strokeheat stroke

GUGU• infertility in malesinfertility in males

DiagnosisDiagnosis

Elevated serum trypsinogen in neonateElevated serum trypsinogen in neonate Gene testingGene testing

• 87 mutation panel (92% sensitivity)87 mutation panel (92% sensitivity)• 1300 mutation panel (97 - 99% sensitivity)1300 mutation panel (97 - 99% sensitivity)

GOLD STANDARD: CHLORIDE SWEAT GOLD STANDARD: CHLORIDE SWEAT TESTTEST• <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

DiagnosisDiagnosis

False positivesFalse positives• adrenal insufficiencyadrenal insufficiency• nephrogenic DInephrogenic DI• hypothyroidismhypothyroidism• mucopolysaccharidomucopolysaccharido

sissis• G6P deficiencyG6P deficiency• hypoproteinemiahypoproteinemia• anemia from poor anemia from poor

nutritionnutrition

False negativesFalse negatives• severe severe

malnutrition with malnutrition with edemaedema

• too little sweattoo little sweat• inexperienced inexperienced

testertester

TreatmentTreatment

For acute respiratory infections: For acute respiratory infections: hospitalization with PCN and hospitalization with PCN and aminoglycoside, pulmonary toiletaminoglycoside, pulmonary toilet

baseline pulmonary therapybaseline pulmonary therapy• aerosols (bronchodilation)aerosols (bronchodilation)• chest physical therapychest physical therapy• aerosolized antibioticsaerosolized antibiotics• systemic steroids or expectorants--not systemic steroids or expectorants--not

indicatedindicated

TreatmentTreatment

Nutritional therapyNutritional therapy• high fat, high protein diethigh fat, high protein diet• pancreatic enzyme replacementspancreatic enzyme replacements• vitamin and mineral supplementsvitamin and mineral supplements

OtherOther• no support for growth hormoneno support for growth hormone• pulmonary transplant--must pulmonary transplant--must

transplant both lungs simultaneously!transplant both lungs simultaneously!

PrognosisPrognosis

Life expectancy of about 32 years Life expectancy of about 32 years at bestat best

Poorer prognosis in:Poorer prognosis in:• femalesfemales• low SESlow SES• severe neonatal pulmonary diseasesevere neonatal pulmonary disease