Nejm 1997;336:487; 1996;335:179; 1993;328:1390

Cause:Genetic mutations of the CF transmembrane conductance regulator gene (CFTR) on chromosome #7; autosomal with variable penetrance (Nejm 2005;352:1992)

Pathophys:Deficient chloride^– secretion and excessive Na+ resorption across epithelial surfaces (Nejm 1991;325:533). Exocrine gland fibrosis in homozygote; pancreatic duct obstruction causes pancreatic insufficiency (Nejm 1985;312:329). Bronchi obstructed leading to secondary infections, esp with staph and pseudomonas, COPD, and pulmonary failure. Vas deferens obstruction/absence causes male sterility (98%) (Nejm 1972;287:586); nothing analogous in female. Sweat glands obstructed causing an inability to lose heat

Caucasians have 98.4% of all cystic fibrosis; 1/30 000 whites in US; heterozygotes about 5% of population. Blacks have a 1.4% prevalence of heterozygote; all other racial groups have a prevalence <0.2%; only 1 reported case in Asian (Nejm 1968;279:1216)

Sx:COPD; heat exhaustion; malabsorption sx; sterility, esp male (90%), which may be only sx (Nejm 1995;332:1475)

Si:Meconium ileus at birth (15%); no sweat; malnourished; severe chronic bronchitis and pulmonary insufficiency

Depends on age of onset and complications; 2-yr mortality >50% once FEV1 % becomes <30% of predicted, PaO₂ <55 mm Hg or pCO₂ >50 mm, so begin planning lung transplant then (Nejm 1992;326:1187)

COPD, bronchiectasis, pneumothorax (20% lifetime incidence), massive hemoptysis (7% get in lifetime); growth retardation; pancreatic insufficiency (80%); diabetes mellitus (20%) without vascular lesions (Nejm 1969;281:451); rectal prolapse, may be presenting sx; gallstones, in 50% by age 26 yr, w common bile duct obstruction (15-20%) (Nejm 1988;318:340); modest increase in gi cancers in adulthood (Nejm 1995;332:494); osteoporosis w fx’s and kyphosis in adulthood (Ann IM 1998;128:186)

Lab:

Bact: S. aureusin sputum and/or nasal pharynx; pseudomonas or E. coli,in sputum both of which produce a mucoid material almost pathognomonic of CF (Nejm 1981;304:1445)

Chem:Sweat tests with or without pilocarpine stimulation; characteristically Cl >60 mEq/L, usually >80, r/o Addison’s, atopic dermatitis, malnutrition, hypothyroidism, and a few rare others (Nejm 1997;336:487). Duodenal aspirate shows diminished pancreatic enzyme secretion and pH <8 even after secretin stimulation

Noninv:PFTs show diminished vital capacity, increased residual volume

Semen analysis:azoospermia

Xray:Sinus films show opacified paranasal sinuses

Rx:

Prevent by carrier detection with tissue culture (Nejm 1981;304:1); but not practical to screen entire Caucasian population yet (Nejm 1990;322:328). In affected families, in vitro fertilization and preimplantation testing possible (Nejm 1992;327:905)

Screen newborns maybe w blood trysinogen levels since may eventually be reasonable to institute dietary and pulmonary interventions early (Nejm 1997;337:963)

Lung transplants (Jama 2001;286:2683) ineffective in children (Nejm 2007;357:2143)

of cmplc:

• Pulmonary, rx same as COPD, consider:
• Prophylactic antibiotics like ciprofloxacin or azithromycin (Jama 2003;290:1749), which has anti-inflammatory properties, or antibiotic aerosols like tobramycin (Nejm 1999;340:23) for pseudomonas; but antibiotic management is complex esp in end stages
• Hypertonic saline (7%) nebs bid-qid dramatically decr exacerbations (Nejm 2006;354:229, 241, 291)
• Amiloride (Midamor) inhaler qid slows progression, perhaps by blocking Na resorption and thus thinning mucus (Nejm 1990;322:1189); but blocks benefit of inh hypertonic saline
• Avoid smoke exposure, eg, in home (Nejm 1990;323:782);
• Acetylcysteine (Mucomyst) and alpha dornase (Pulmozyme) DNAase inhaler qd-bid, significantly thins secretions (Nejm 1994;331:637; 1992;326:812) and modestly improves PFTs, and decreases infections, but inhaler without medication costs $2000 and total cost/yr used qd is $12 000 (Med Let 1994;36:34); but cheap po form may work (ACP J Club 2002;136:54)
• Ibuprofen 25 mg/kg qd chronically slows progression (Nejm 1995;332:848)
• Pancreatic enzyme replacement (Chronic Pancreatitis and Pancreatic Insufficiency)
• Intestinal obstruction w Gastrografin enema, which increases gi fluid