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.
We have used a short-acting beta 2-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 hyperresponsiveness. Pretreatment with inhaled rimiterol hydrobromide 400 microgram 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 FEV 3 to 8 h after allergen challenge (Lmax) of less than 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 greater than 15% from premedication baseline value. For the whole group, there was a significant increase in the magnitude of LAR whether calculated as Lmax (p less than 0.05) or as area under the FEV1 time response curve between 3 and 8 h postchallenge (p less than 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 less than 0.05 on control day, p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lai
C K
CK
Immunopharmacology Group, Southampton General Hospital, United Kingdom.
Twentyman
O P
OP
Holgate
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ST
D000328:Adult; D000368:Aged; D000485:Allergens; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D002396:Catechols / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology*; D013147:Spirometry; D013997:Time Factors
D000485:Allergens; D002396:Catechols; D008688:Methacholine Compounds; D010880:Piperidines; D016210:Methacholine Chloride; C084590:rimiterol