Cystic Fibrosis: A Brief Review of Pathogenesis, Clinical Features, Diagnosis and Therapies

Cystic fibrosis (CF) is an autosomal recessive disorder caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes CFTR protein, a chloride and bicarbonate channel essential for epithelial ion transport. CF occurs across all racial and ethnic groups, though incidence is highest among individuals of Northern European ancestry. Advances in newborn screening, diagnosis, and treatment have transformed CF from a fatal childhood disease into a chronic, manageable condition extending into adulthood. Over 2000 CFTR variants have been identified and classified into six groups based on their impact on protein production, processing, and function. Variants in Classes I–III generally result in more severe disease, while Classes IV–VI are associated with milder phenotypes. CF primarily affects the lungs, pancreas, gastrointestinal tract, hepatobiliary system, and reproductive system. Progressive pulmonary disease remains the leading cause of morbidity and mortality, driven by mucus obstruction, chronic infection, and neutrophil-mediated inflammation. Pancreatic insufficiency, malabsorption, CF-related diabetes, liver disease, and infertility are common systemic features. Modern management combines symptomatic therapies with CFTR modulators such as ivacaftor and triple-combination regimens which have revolutionized outcomes. Median survival now exceeds 50 years, with ongoing research targeting universal therapies and gene-based approaches.