Pharmacological therapy of cystic fibrosis basic defect

Background: Cystic fibrosis (CF) is characterized by abnormal ion transport in various epithelia (1, 2).
Mutations in CF patients cause loss of function of CFTR, a plasma membrane protein involved in cAMP-dependent Cl- secretion. CFTR defect causes obstruction of airway submucosal glands and pancreatic ducts. It is believed that CFTR has also the ability to reduce, through a regulatory mechanism, the extent of Na+ absorption occurring through the ENaC channel (3).
In the surface epithelium of the airways, combination of defective Cl- secretion and excessive Na+ absorption causes a reduction of the periciliary fluid (PCF) volume with a consequent collapse of the mucous layer entrapping the cilia (4). The consequent impairment of the mucociliary clearance would favor the bacterial colonization of the airways. It is also possible that bacterial persistence in the CF airways is caused by the obstruction of submucosal glands which cannot secrete proteins with antimicrobial activity (5)…