Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice.

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.

Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia.

Intranasal instillation techniques are used to deliver various substances to the upper and lower respiratory tract (URT and LRT) in mice. Here, we quantify the relative distribution achieved with intranasal delivery of a nonabsorbable tracer, (99m)Tc-labeled sulfide-colloid. Relative distribution was determined by killing mice after instillation and quantifying the radioactivity in dissected tissues using gamma scintigraphy. A significant effect of delivery volume on relative distribution was observed when animals were killed 5 min after instillation delivered under gas anesthesia. With a delivery volume of 5 microl, no radiation was detected in the LRT; this increased to a maximum of 55.7 +/- 2.5% distribution to the LRT when 50 microl were delivered. The majority of radiation not detected in the LRT was found in the URT. Over the course of the following 1 h, radiation in the LRT remained constant, while that in the URT decreased and appeared in the gastrointestinal tract. Instillation of 25 microl into anesthetized mice resulted in 30.1 +/- 6.9% distribution to the LRT, while only 5.3 +/- 1.5% (P < 0.05) of the same volume was detected in the LRT of awake mice. Varying the body position of mice did not affect relative distribution. When using intranasal instillation, the relative distribution between the URT and LRT and the gastrointestinal tract is heavily influenced by delivery volume and level of anesthesia.