Cystic Fibrosis
Pulmonary and Critical Care Medicine · Airways Disease 🎯 Practice these cards
Cystic fibrosis is inherited in a(n) ____ pattern, occurs in approximately 1 of ____ live births, and is most often caused by the ____ mutation.
Cystic fibrosis is an autosomal recessive CFTR exocrinopathy diagnosed in ~1 of 2000–3000 live births (most common in European descent; ~1/3300 white US births). The F508del (ΔF508) variant is the most common of >2000 described CFTR alleles.
CFTR is an ATP-gated epithelial ____ channel on the ____ membrane; its loss depletes the ____ layer, causing ciliary collapse and mucus stasis.
CFTR is an ATP-gated epithelial anion channel conducting chloride and bicarbonate across the apical membrane. In airways it maintains the periciliary fluid (PCL) layer needed for ciliary extension and mucociliary clearance; CFTR loss depletes the PCL, collapsing cilia and stalling mucus clearance.
CFTR mutation classes: I = no protein synthesis; II = ____ (F508del); III = ____ (G551D); IV = pore conductance; V = ____; VI = accelerated turnover.
Class I: no protein synthesis (nonsense — G542X, W1282X). Class II: defective maturation/trafficking (F508del — the most common). Class III: defective gating (G551D). Class IV: impaired pore conductance. Class V: reduced transcript (splicing/promoter). Class VI: accelerated surface turnover.
The F508del mutation accounts for approximately ____% of defective CFTR alleles in the US and is a class ____ defect.
F508del accounts for ~85% of defective CFTR alleles in the United States. It is a class II defect: the protein retains partial channel function but is arrested in the endoplasmic reticulum and degraded by the proteasome.
The sweat chloride test uses ____ iontophoresis; a value ≥____ mEq/L on repeat testing is diagnostic; in adults a negative result ____ rule out CF.
Sweat chloride by pilocarpine iontophoresis: ≥60 mEq/L on repeat testing is diagnostic (highly specific). Less sensitive in adults — a negative result does NOT rule out CF; proceed to CFTR genotyping or CF-center referral if suspicion persists.
US newborn screening for CF measures blood ____; a positive screen is confirmed by ____ analysis and/or sweat electrolytes.
Universal US newborn screening measures blood immunoreactive trypsinogen (IRT) — elevated because of exocrine pancreatic damage — followed by confirmatory CFTR mutation analysis and/or sweat electrolytes. Most CF is now diagnosed this way rather than by the classic childhood triad (cough, steatorrhea, failure to thrive).
In CF, P. aeruginosa colonization typically persists for life with the same genetic strain; evolution to a ____ phenotype (from ____ production) confers a poor prognosis.
A sentinel colonization event typically establishes lifelong P. aeruginosa infection with the same genetic strain; over years it evolves to a mucoid, alginate-producing phenotype conferring pathogen advantage and poor host prognosis. CF sinuses serve as a bacterial reservoir for the lower airways.
Poor-prognosis CF organisms include ____ complex, Stenotrophomonas maltophilia, Achromobacter, ____ P. aeruginosa, atypical mycobacteria, and ____.
Rigorously monitored organisms associated with worse outcomes: Burkholderia cepacia complex, Stenotrophomonas maltophilia, Achromobacter, mucoid P. aeruginosa, atypical (nontuberculous) mycobacteria, and MRSA.
Exocrine pancreatic insufficiency affects approximately ____% of CF patients; CF-related diabetes occurs in >____% of adults and requires ____ screening.
Exocrine pancreatic insufficiency affects ~80% of CF patients (malabsorption, steatorrhea, low fecal elastase-1, fat-soluble vitamin deficiency). CF-related diabetes affects >30% of adults from progressive islet loss; annual diabetes screening is recommended.
Approximately ____% of men with CF are infertile from congenital bilateral absence of the ____; spermatogenesis is typically ____.
~99% of men with CF are infertile from congenital bilateral absence/involution of the vas deferens (obstructive azoospermia), but spermatogenesis is preserved — sperm retrieval with IVF enables biological parenthood.
The pillars of CF management are airway clearance, ____ therapy, ____ support, and psychosocial support; dornase alfa works by degrading ____ in mucus.
Four pillars coordinated at a CF care center: airway clearance (chest physiotherapy, hypertonic saline/mannitol, dornase alfa), antibiotics (inhaled tobramycin maintenance for Pseudomonas, oral macrolides), nutritional support (pancreatic enzymes with meals, fat-soluble vitamins), and psychosocial support.
Ivacaftor is a CFTR ____ (effective for G551D), whereas lumacaftor, tezacaftor, and elexacaftor are ____; the elexacaftor-based triple benefits >____% of patients.
Ivacaftor = potentiator (opens gated channels; G551D class III; ~97 approved variants; first drug to normalize sweat chloride). Lumacaftor/tezacaftor/elexacaftor = correctors (rescue F508del folding). Elexacaftor–tezacaftor–ivacaftor triple covers >90% of patients (≥1 F508del allele) with ~14-point ppFEV1 gains.
FDA-approved in December 2024, ____ (vanzacaftor/tezacaftor/deutivacaftor) is the first ____-daily CFTR modulator triple, for patients aged ≥____ years.
Vanzacaftor/tezacaftor/deutivacaftor (Alyftrek), FDA-approved December 20, 2024, is the second CFTR-modulator triple and the first dosed once daily — for patients ≥6 years with ≥1 F508del or another responsive mutation. SKYLINE 102/103: non-inferior ppFEV1 vs elexacaftor triple, superior sweat-chloride reduction over 52 weeks.
Severe CF exacerbations are treated with parenteral antibiotics for approximately ____ days (aminoglycoside plus a ____ for Pseudomonas); failure to respond should prompt evaluation for ____.
Severe exacerbations: hospital admission, parenteral combination antibiotics (aminoglycoside + antipseudomonal β-lactam for Pseudomonas) for ~14 days, frequent chest physiotherapy; maximal improvement often by 8–10 days. Failure to respond to aggressive antibiotics should prompt evaluation for ABPA (~5% of CF).
Lung transplant referral is considered when FEV1 falls below ____% predicted; median adult survival after CF lung transplantation exceeds ____ years.
Transplant referral is considered at FEV1 <30% predicted (earlier with pulmonary hypertension, rapid decline, or frequent hospitalizations); evaluation is underused and best started early. Median adult post-transplant survival exceeds 9 years.
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