An overview of the pathogenesis of cystic fibrosis lung disease

RC Boucher - Advanced drug delivery reviews, 2002 - Elsevier
Advanced drug delivery reviews, 2002Elsevier
The pathogenesis of cystic fibrosis (CF) lung disease is reviewed, focusing on an overview
of the physiologic mechanisms that regulate mucus transport. A major emphasis is placed
on the active transport systems that regulate the airway surface liquid (ASL) volume and,
particularly, regulate the volume of the periciliary liquid (PCL) layer. A sequence is
developed for CF whereby there is a depletion of the PCL that reflects the combined
dysfunctions of accelerated Na+-dependent volume absorption and failure to secrete Cl …
The pathogenesis of cystic fibrosis (CF) lung disease is reviewed, focusing on an overview of the physiologic mechanisms that regulate mucus transport. A major emphasis is placed on the active transport systems that regulate the airway surface liquid (ASL) volume and, particularly, regulate the volume of the periciliary liquid (PCL) layer. A sequence is developed for CF whereby there is a depletion of the PCL that reflects the combined dysfunctions of accelerated Na+-dependent volume absorption and failure to secrete Cl. Both dysfunctions are a direct consequence of missing cystic fibrosis transmembrane conductance regulator (CFTR) at the apical membrane of airway epithelial cells. PCL depletion leads to failure of mucus transport, which is associated with persistent mucin secretion and formation of adherent mucus plaques and plugs. These plugs become the nidus for persistent bacterial airway infections that ultimately lead to a markedly anaerobic luminal environment.
Elsevier