Cystic fibrosis
Cystic fibrosis is an autosomal recessive CFTR chloride-channel disorder causing thick secretions, bronchiectasis, and exocrine pancreatic insufficiency, diagnosed by elevated sweat chloride confirmed with CFTR genotyping and managed with CFTR modulators, airway clearance, and pancreatic enzyme replacement.
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What this article covers
- Overview
Autosomal recessive CFTR channelopathy: cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene on chromosome 7, an epithelial chloride channel; the…
- Epidemiology
The most common severe genetic disease in the United States, occurring in approximately 1 of 2,000 to 3,000 live births, with a strong predilection for individuals of Northern European descent.
- Risk factors
Family history of CF or a known CFTR carrier in a sibling is the strongest identifiable risk factor and should prompt genetic counseling and testing.
- Pathophysiology
Loss of functional CFTR chloride transport at the apical epithelial membrane impairs chloride, bicarbonate, and water movement across exocrine epithelia, producing thick, dehydrated secretions.
- Clinical features
Chronic productive cough is the most common pulmonary symptom and, with recurrent sinopulmonary infections, dominates the presentation in older children and adults.
- Differential diagnosis
Primary ciliary dyskinesia: bronchiectasis and chronic sinusitis with normal sweat chloride; distinguished by nasal nitric oxide and ciliary ultrastructure/genetic testing; associated with situs abnormalities.
- Diagnosis
Diagnostic criteria require at least one clinical/risk criterion plus a CFTR abnormality: at least one phenotypic feature (chronic pulmonary disease, chronic sinusitis, GI/nutritional abnormalities…
- Management
Confirm CFTR genotype first, since it determines eligibility for disease-modifying CFTR modulator therapy, in every newly diagnosed patient and any previously diagnosed patient not yet genotyped.
- Complications
Bronchiectasis with recurrent infection and progressive airflow obstruction is the dominant driver of morbidity and, over years, respiratory failure.
- Prognosis
Median survival has risen from approximately 20 years historically to past 40 years with modern multidisciplinary care and CFTR modulator therapy, and continues to improve.
- Prevention
Newborn screening (immunoreactive trypsinogen, followed by sweat chloride or CFTR mutation testing for a positive screen) is standard in the United States and enables diagnosis before symptomatic disease develops.
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