Front-runners for pharmacotherapeutic correction of the airway ion transport defect in cystic fibrosis.

摘要

Although cystic fibrosis (CF) patients display multiorgan dysfunction (e.g. pancreas, gut, and lung) it is lung disease that is the leading cause of premature death in these patients. CF lung disease is characterized by persistent pulmonary infection and mucus plugging of the airways initiated by the failure of solute transport across the airway epithelium. Many drug therapies aim to alleviate the secondary characteristics of CF lung disease; however, new therapies in development are targeted at correcting the ion transport deficiency of CF. The goal is to hydrate airway surfaces by stimulating secretion (through activation of the CF transmembrane conductance regulator and calcium-activated chloride channels), and/or inhibiting absorption (through the epithelial sodium channel) thereby stimulating healthy mucociliary clearance. If mucociliary clearance can be stimulated sufficiently from an early age, then there is the possibility that secondary lung infection may be eradicated from the syndrome of CF disease.