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Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice

¹ Firestone Institute for Respiratory Health, Dept of Medicine, McMaster University, Hamilton, ON, Canada, ² AstraZeneca, Research and Development, Charnwood, Loughborough, UK.

CORRESPONDENCE: M. D. lnman, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6, Canada. Fax: 1 9055406510. E-mail: inmanma{at}mcmaster.ca

Keywords: Airway hyperresponsiveness, asthma, bronchial hyperreactivity, corticosteroid treatment, pathophysiology, remodelling

Received: September 23, 2007
Accepted April 30, 2008

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

Mice were chronically exposed to allergen and treated with budesonide either: 1) briefly during the final weeks of exposure to allergen; 2) prolonged concurrently throughout exposure to allergen; or 3) delayed following final exposure to allergen. AHR was assessed 24 h (brief treatment) or 4 weeks (prolonged concurrent and delayed treatments) following final exposure to allergen.

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

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.