Cystic Fibrosis: Pathophysiology, Pharmacotherapy, CFTR Modulators and Emerging Therapeutic Strategies—A Contemporary Review

Cystic fibrosis (CF) is an autosomal recessive multisystem disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Defective CFTR-mediated chloride and bicarbonate transport produces dehydrated epithelial secretions, impaired mucociliary clearance, chronic airway infection and inflammation, pancreatic insufficiency and other systemic complications. Conventional therapy focuses on airway clearance, mucolysis, antimicrobial treatment, nutritional support and complication management. CFTR modulators have changed the therapeutic paradigm by targeting the underlying molecular defect. Ivacaftor acts principally as a potentiator, whereas lumacaftor, tezacaftor and elexacaftor act as correctors. Combination regimens, especially elexacaftor/tezacaftor/ivacaftor, produce clinically important improvements in lung function, sweat chloride, exacerbation frequency and quality of life in eligible patients. Pharmacokinetic interactions, hepatic monitoring, adherence, genotype-specific eligibility, cost and unequal access remain important limitations. Newer small-molecule combinations and mutation-agnostic approaches, including mRNA replacement, gene transfer and gene editing, aim to extend disease-modifying therapy to people who do not benefit adequately from existing modulators. This review summarizes CF pathophysiology, diagnosis, conventional pharmacotherapy, CFTR modulators, safety considerations and emerging therapies, with emphasis on concepts relevant to pharmaceutical sciences.