Lai C K, Twentyman O P, Holgate S T
Immunopharmacology Group, Southampton General Hospital, United Kingdom.
Am Rev Respir Dis. 1989 Oct;140(4):917-23. doi: 10.1164/ajrccm/140.4.917.
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)
我们使用了一种短效β2肾上腺素能受体激动剂氢溴酸瑞米特罗,以便能给之前的单一“早期过敏原反应者”给予更大剂量的过敏原,来研究增加过敏原剂量是否会诱发迟发性哮喘反应(LAR),以及这是否会影响随后获得的过敏原诱导的非特异性支气管高反应性水平。对8名轻度哮喘的特应性受试者进行预处理,吸入400微克氢溴酸瑞米特罗,这些受试者最初被归类为单一早期反应者,过敏原激发后8小时FEV₃最大下降(Lmax)小于基线值的15%,这使得吸入的过敏原剂量几何平均数增加了8.9倍(范围为2至29.1)。早期哮喘反应的程度与在无氢溴酸瑞米特罗情况下进行过敏原激发的对照日所获得的程度相似。5名受试者转变为双重过敏原反应者,Lmax比用药前基线值增加超过15%。对于整个组,无论以Lmax计算(p小于0.05)还是以激发后3至8小时FEV₁时间反应曲线下面积计算(p小于0.01),LAR的程度都有显著增加。激发后8小时引起FEV₁下降20%的乙酰甲胆碱激发浓度(PC20),与相应的激发前值相比,在两天均显著降低(对照日p小于0.05,氢溴酸瑞米特罗日p小于0.01)。然而,尽管在氢溴酸瑞米特罗日LAR的程度增加,但激发后PC20的降低与对照日相比并无显著差异。(摘要截短于250字)