Cough induced by changes of ionic composition of airway surface liquid

Coughing is one of the most common of respiratory systems, and yet few anti-tussives are wholly effective and safe. Centrally acting anti-tussives not only inhibit coughing, but also depress ventilation. As an alternative approach, therapies acting on the afferent limb of the cough reflex are explored. Coughing can be reflexly induced in man by reducing the chloride ion content of airway surface lining liquid (ASL). This can be achieved by inhaling aerosols of hypochloride aqueous solutions nebulized ultrasonically. The cough reflex so provoked may be an important protective mechanism to prevent wide excursions of ionic content of ASL. We have demonstrated that pretreatment with inhaled beta-sympathomimetic and anti-muscarinic drugs inhibit this cough reflex whilst oral beta-sympathomimetics and anti-muscarinics have less effect. It is unlikely that either group of drugs directly affect the vagal epithelial receptors responsible for the cough reflex induced by hypochloride solutions. We hypothesize that these agents may act by limiting the communication between the ASL and the paracellular channels, where the receptors lie between the epithelial cells, by tightening the junctions between cells. This may also explain why beta-sympathomimetic agents inhibit the cough of viral infections and the cough of asthma.