Mucus Transpiration as the Basis for Chronic Cough and Cough Hypersensitivity

Chronic cough is characterized by a state of cough hypersensitivity. We analyze the process of transpiration, by which water appears to evaporate from laryngeal and tracheal mucus as from the surface of a leaf, as a potential cause of cough hypersensitivity. In this process, osmotic pressure differences form across mucus, pulling water toward the air, and preventing mucus dehydration. Recent research suggests that these osmotic differences grow on encounter with dry and dirty air, amplifying pressure on upper airway epithelia and initiating a cascade of biophysical events that potentially elevate levels of ATP, promote inflammation and acidity, threaten water condensation, and diminish mucus water permeability. Among consequences of this inflammatory cascade is tendency to cough. Studies of isotonic, hypotonic, and hypertonic aerosols targeted to the upper airways give insights to the nature of mucus transpiration and its relationship to a water layer that forms by condensation in the upper airways on exhalation. They also suggest that, while hypertonic NaCl and mannitol may provoke cough and bronchoconstriction, hypertonic salts with permeating anions and non-permeating cations may relieve these same upper respiratory dysfunctions. Understanding of mucus transpiration and its role in cough hypersensitivity can lead to new treatment modalities for chronic cough and other airway dysfunctions promoted by the breathing of dry and dirty air.