The Effect of an Increase in Inhaled Allergen Dose after Rimiterol Hydrobromide on the Occurrence and Magnitude of the Late Asthmatic Response and the Associated Change in Nonspecific Bronchial Responsiveness

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Abstract
We have used a short-acting β2-adrenoceptor agonist, rimiterol hydrobromide, to allow a larger dose of allergen to be administered to previous single “early allergen responders” to investigate if an increased dose of allergen could induce a late asthmatic response (LAR) and whether this would influence the subsequent level of allergen-acquired nonspecific bronchial hyperrespon-siveness. Pretreatment with inhaled rimiterol hydrobromide 400 µg enabled an increase in allergen dose inhaled by a geometric mean of 8.9-fold (range, 2 to 29.1) in eight atopic subjects with mild asthma who initially were classified as single early responders with a maximal fall in FEV1 3 to 8 h after allergen challenge (Lmax) of < 15% from baseline value. The magnitude of the early asthmatic response was similar to that obtained on the control day when allergen challenge was performed in the absence of rimiterol hydrobromide. Five subjects were converted to dual allergen responders with Lmax of > 15% from premedication baseline value. For the whole group, there was a significant increase in the magnitude of LAR whether calculated as Lmax (p < 0.05) or as area under the FEV1-time response curve betwen 3 and 8 h postchallenge (p < 0.01). The provocation concentrations of methacholine causing a 20% fall in FEV1 (PC20) at 8 h postchallenge were significantly reduced on both days when compared with the corresponding prechallenge values (p < 0.05 on control day, p < 0.01 on rimiterol day). However, despite the increase in the magnitude of LAR on the rimiterol day, the reduction in postchallenge PC20 did not differ significantly from that occurring on the control day. These results indicate that an increase in allergen dose can lead to the occurrence of LARs without producing a further change in allergen-acquired nonspecific bronchial hyperresponsiveness.

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