Pathophysiology
CFTR gene mutations on chromosome 7 (F508del most common, ~70%) misfold the chloride channel, reducing airway surface liquid and increasing mucus viscosity. Impaired mucociliary clearance predisposes to Pseudomonas aeruginosa and Staphylococcus aureus infection.
Sources: CFF Pulmonary Clinical Care Guidelines (Am J Respir Crit Care Med 2023;207:1288); CFF Nutrition & GI Guidelines (J Cyst Fibros 2023;22:583); NEJM Elexacaftor-Tezacaftor-Ivacaftor (2019;381:1809)
Clinical presentation
Meconium ileus at birth, recurrent sinopulmonary infections, chronic productive cough, digital clubbing, pancreatic exocrine insufficiency (steatorrhoea, failure to thrive, fat-soluble vitamin deficiency), male infertility (CBAVD), and CF-related diabetes.
Diagnosis
Newborn immunoreactive trypsinogen screen; confirm with sweat chloride >=60 mmol/L on two occasions or two disease-causing CFTR mutations. Genotype guides modulator eligibility.
Management
Airway clearance (postural drainage, hypertonic saline, dornase alfa), inhaled antibiotics (tobramycin) for chronic Pseudomonas, pancreatic enzyme replacement (PERT), high-calorie diet with ADEK vitamins, and CFTR modulators - elexacaftor/tezacaftor/ivacaftor for patients >=2 y with >=1 F508del allele.
Complications
Chronic Pseudomonas/Burkholderia infection, pulmonary exacerbations, pneumothorax, haemoptysis, CF-related diabetes, distal intestinal obstruction syndrome, hepatobiliary disease, and osteoporosis.
