Enhancement of goblet cell hyperplasia and airway hyperresponsiveness by salbutamol in a rat model of atopic asthma

Background-Goblet cell hyperplasia (GCH) is a prominent feature in animal m odels of atopic asthma produced by immunisation and following multiple chal lenges with antigens. The aim of this study was to examine the effect of a beta (2) agonist on the development of GCH induced by the immune response. Methods-Brown Norway rats were immunised and challenged with an aerosol of ovalbumin for four weeks. Salbutamol (0.5 mg/kg/day) or vehicle was continu ously delivered for the four weeks using a subcutaneously implanted osmotic minipump. The density of goblet cells, other morphological changes, and ai rway responsiveness to methacholine were evaluated 24 hours after the final challenge. Results-Treatment with salbutamol induced a more than twofold increase in t he mean (SE) number of goblet cells (53.7 (7.3) vs 114.5 (11.8) cells/10(3) epithelial cells, p<0.01) while it did not significantly influence airway wall thickening and eosinophilic infiltration. Airway responsiveness to met hacholine expressed as the logarithmic value of the concentration of methac holine required to generate a 50% increase in airway pressure (logPC(150)Mc h) was also enhanced by the <beta>(2) agonist (-0.56 (0.21) vs -0.95 (0.05) , p<0.05). Additional experiments revealed that the same dose of the <beta> (2) agonist alone did not cause GCH in non-immunised rats and that the enha ncement of GCH by salbutamol was completely abolished by simultaneous treat ment with methylprednisolone (0.5 mg/kg/day). Conclusions-These data suggest that salbutamol enhances goblet cell hyperpl asia and airway hyperresponsiveness in this rat model of atopic asthma.