Cystic Fibrosis as a Multisystem Disease: Pathophysiology, Diagnosis, and Advances in CFTR-Targeted Therapy

Cystic fibrosis (CF) remains a life-limiting and multisystem genetic disease with high morbidity and mortality, making it a critical focus of biomedical research. It affects tens of thousands of individuals worldwide. It leads to progressive organ dysfunction, particularly in the lungs and pancreas, resulting in chronic respiratory infections, pancreatic insufficiency, and reduced life expectancy. CF’s complex disease mechanisms, involving more than 2,000 distinct CFTR gene mutations, contribute to its heterogeneous clinical expression and systemic impact across multiple organs, including the gastrointestinal and hepatobiliary systems. Furthermore, populations in low-resource settings face high morbidity and mortality due to underdiagnosis and delayed treatment, underlining the global need for improved understanding and interventions. Historically, cystic fibrosis management emphasized prevention and treatment of disease complications. Advances in CFTR-modulating therapies now enable the direct correction of the underlying ion channel defect, representing a significant shift in care. Assessing the long-term effects of emerging therapies on disease progression and patient quality of life is critical as CFTR-targeted treatments continue to transform clinical practice and research paradigms. Continued investigation is therefore essential not only to optimize existing therapeutic approaches but also to develop more effective, accessible, and mutation-inclusive treatments, alongside improved strategies for early diagnosis, disease monitoring, and sustained enhancement of patient quality of life.