Clinical meaning
Cystic fibrosis (CF) is caused by mutations in the CFTR gene encoding the CF transmembrane conductance regulator — a chloride and bicarbonate channel on epithelial cell surfaces. The most common mutation, F508del (70% of alleles), causes protein misfolding, ER retention, and proteasomal degradation. Defective CFTR reduces chloride and water secretion into airway lumen while increasing sodium reabsorption via ENaC (epithelial sodium channel), producing thick, dehydrated mucus. In the lungs, this impairs mucociliary clearance, creating a favorable environment for chronic bacterial colonization (Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia). In the pancreas, duct obstruction causes pancreatic insufficiency (85-90%). CFTR modulators (elexacaftor/tezacaftor/ivacaftor — Trikafta) have transformed CF from a pediatric disease to an adult chronic disease, with median predicted survival now exceeding 50 years.
Diagnosis & workup
Diagnostics & workup: - Sweat chloride test: ≥60 mmol/L diagnostic (30-59 intermediate, <30 normal) - CFTR genotyping: identifies specific mutations (guides CFTR modulator eligibility) - Pulmonary function tests: FEV1 is the primary outcome measure (goal >80% predicted) - Sputum culture: identify bacterial colonization (P. aeruginosa, MRSA, B. cepacia) - Annual OGTT: screen for CFRD (unique diabetes — insulin deficient with preserved glucagon) - Fecal elastase: <200 mcg/g confirms pancreatic insufficiency - Chest CT: bronchiectasis assessment (more sensitive than CXR) - BMI monitoring: target >22 in adults with CF - Bone density (DEXA): CF-related osteoporosis screening