Ongoing research into other emerging therapies

Critical to the normal function of airways, the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a chloride (Cl-) channel that regulates activity of other ion channels, including epithelial sodium (Na+) channel (ENaC), calcium-activated Cl- channel (CaCC), outwardly rectifying Cl- channel, and Cl- channel 2 (CLC2). Reduction or elimination of CFTR results in disruption of Cl- secretion and excessive Na+ reabsorption, ultimately leading to depleted airway surface liquid depth, poor ciliary function, and impaired mucociliary clearance. This discussion details ion channel activity within normal versus CF airways and provides a review of alternative Cl- channel agonists, Na+ channel blockers, and novel osmotic agents. Current Cl- channel agonists under development are known to activate either the CaCC or the CLC2, which provide alterative pathways to increase Cl- and mucin secretion. ENaC inhibitors are known to dampen Na+ reabsorption, leading to improved airway surface liquid depth, and ultimately, mucociliary and cough clearance.