Pathophysiology of Cystic Fibrosis

Understanding the development of lung disease in cystic fibrosis (CF) has been a sought after goal for several decades. With the cloning of the CF transmembrane conductance regulator (CFTR) gene and other advances in the study of airway epithelial biology, a much clearer picture of disease pathophysiology has emerged. Our best available evidence points to dysregulated ion transport as the underlying defect that causes depletion of airway surface liquid volume, i.e. dehydration, and an associated impairment in mucus clearance. Mucostasis in turn predisposes the CF lung to bacterial infection, which rapidly becomes chronic due to the nature of the CF secretions themselves. The nonresolving neutrophilic inflammatory response to this chronic infection in turn causes progressive and permanent airway damage, such that bronchiectasis and respiratory failure are the common findings in end-stage CF lung disease. Hopes of preventing this cascade of events are provided by the development of new therapies that address the underlying defect of airway dehydration.