Budesonide Prevents but Does Not Reverse Sustained Airway Hyperresponsiveness in Mice

¹ Firestone Institute for Respiratory Health, Dept of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 4A6
² AstraZeneca, R&D Charnwood, Loughborough, United Kingdom LE11 5RH

^* To whom correspondence should be addressed. E-mail: southads{at}mcmaster.ca.

	Abstract

Despite the effectiveness of corticosteroids at resolving airway inflammation, they are only moderately effective at attenuating airway hyperresponsiveness. The extent to which corticosteroids are able to reverse, or inhibit the development of, sustained airway hyperresponsiveness is not known. This study aimed to determine if budesonide can resolve and or prevent the development of sustained airway hyperresponsiveness in mice.

In this study, mice were chronically exposed to allergen and treated with budesonide either: (i) briefly during the final weeks of exposure to allergen, (ii) prolonged concurrent throughout exposure to allergen, or (iii) delayed following final exposure to allergen. Airway hyperresponsiveness was assessed 24h (brief treatment) or 4wk (prolonged concurrent and delayed treatments) following final exposure to allergen.

Brief budesonide intervention significantly attenuated the inflammation-associated airway hyperresponsiveness assessed immediately following final exposure to allergen. Similarly, prolonged concurrent budesonide treatment prevented the development of sustained airway hyperresponsiveness. Delayed budesonide intervention, however, did not resolve sustained airway hyperresponsiveness.

In conclusion, the early introduction, and importantly the persistence, of corticosteroid treatment prevented the development of sustained airway hyperresponsiveness; however, the inability of corticosteroids to reverse established airway dysfunction indicates a limitation in their use for the complete long-term management of airway hyperresponsiveness.