Ambroxol inhibits airway hyperresponsiveness induced by ozone in dogs

To follow up previous observations that airway hyperresponsiveness induced by ozone is linked to airway inflammation and particularly to the release of arachidonic acid metabolites, we investigated the effect of ambroxol (a mucoactive and surfactant-stimulating drug that has recently been discovered to inhibit the release of arachidonic acid from cell membrane phospholipids) on airway hyperresponsiveness and bronchoalveolar neutrophilia induced by ozone in dogs. One group of 5 dogs was studied before treatment with nebulized saline and then after exposure to ozone (3 ppm, 1 h); another group of 6 dogs was studied before treatment with ambroxol (100 breaths of a 1% solution) and after exposure to ozone. On each occasion, we measured airway responsiveness to acetylcholine and counted the number of cells in bronchoalveolar lavage fluid. When the dogs were given the saline placebo, ozone induced a marked increase in airway responsiveness to acetylcholine and a marked influx of neutrophils in the airways. When the dogs were given ambroxol, ozone induced the same increase in the number of neutrophils in bronchoalveolar lavage, but did not increase the degree of airway responsiveness to acetylcholine. We conclude that ambroxol inhibits ozone-induced airway hyperresponsiveness in dogs, probably by inhibiting the formation and release of oxygenation products of arachidonic acid from neutrophils.