Effect of experimental airway inflammation on bronchial hyper-responsiveness induced by Broncho-Vaxom in dogs

We studied correlation between airway hyper-responsiveness induced by local exposure to a macrophage inductor Broncho-Vaxom and the development of airway inflammation in dogs. To detect airway inflammation, bronchoalveolar lavage and biopsy of airway mucosa were performed. The airway responsiveness was registered by capnograph measuring gas-exchange disturbances during obstructive reactions provocated by inhalation of various concentrations of acetylcholine aerosol. Broncho-Vaxom generated a protracted airway inflammation characterized by a slight and reversible increase in the number of neutrophils at 24 h after induction, and by a long-lasting influx of macrophages peaked about at the second week. The number of macrophages turned to initial levels 3 weeks later. Macrophages migrating to the bronchoalveolar surface were activated because peroxidase positivity and bearing C3b receptors of these cells increased gradually during the inflammatory process. Airway responsiveness measured at 3, 6 and 24 h after induction did not differ significantly from baseline values, but hyper-responsiveness was developed at 96 h using 0.5 and 1.0% acetylcholine aerosol (p less than 0.01 and p less than 0.001) during the non-purulent, macrophage-mediated inflammation. This situation modelled by Broncho-Vaxom induction is very similar to those observed in children with recurrent obstructive bronchitis. The results suggest that a macrophage-mediated inflammation caused by antigens, infections or pollutants may generate a long-lasting airway hyper-responsiveness.