Giannini D, Carletti A, Dente F L, Bacci E, Di Franco A, Vagaggini B, Paggiaro P L
Second Institute of Internal Medicine, Respiratory Pathophysiology, Pisa, Italy.
Chest. 1996 Dec;110(6):1452-7. doi: 10.1378/chest.110.6.1452.
Long-term treatment with inhaled beta 2-agonists may be associated with a deterioration in asthma control, potentially due to tolerance. Regular use of short-acting beta 2-agonists has been shown to induce tolerance to allergen or adenosine 5'-monophosphate challenge. The aim of the study was to detect the efficacy of a single dose and a short-term treatment with salmeterol, a long-acting beta 2-agonist, to protect against early asthmatic reaction (EAR) to allergen. Eight subjects with mild allergic asthma underwent two treatment periods in which subjects performed an allergen challenge (specific bronchial provocation test) protected by a single dose (50 micrograms) of salmeterol (Salm-1) followed by a second specific bronchial provocation test after regular treatment with salmeterol for 1 week (Salm-2), or a single dose of placebo (Plac-1) and regular treatment (1 week) with placebo (Plac-2). Each subject performed both treatments in a randomized order. Each time allergen challenge was performed 1 h after last drug inhalation and it was stopped when the same provocative dose of allergen of a previous screening allergen challenge was achieved. The maximum decrease in FEV1 and area under curve in the first hour after allergen inhalation were significantly lower in Salm-1 (max delta FEV1 %, median [range]: 4%[0 to 9]) with respect to Salm-2, Plac-1, Plac-2 (24%[13 to 38], 31%[19 to 50], 30%[6 to 44], respectively, p < 0.001); there was no difference among Salm-2, Plac-1 and Plac-2. In Salm-1, all subjects were protected against EAR, whereas in Salm-2 only 2 subjects showed a partial protection. In conclusion the protective effect of a single dose of salmeterol against allergen-induced EAR was lost after regular treatment with salmeterol for 1 week. The clinical relevance of this mechanism remains to be elucidated.
吸入性β2受体激动剂的长期治疗可能与哮喘控制的恶化有关，这可能是由于耐受性所致。已证明定期使用短效β2受体激动剂会导致对过敏原或5'-单磷酸腺苷激发试验产生耐受性。本研究的目的是检测单剂量和短期使用长效β2受体激动剂沙美特罗预防过敏原引起的早期哮喘反应（EAR）的疗效。八名轻度过敏性哮喘患者经历了两个治疗阶段，在这两个阶段中，患者先接受单剂量（50微克）沙美特罗（Salm-1）保护下的过敏原激发试验（特异性支气管激发试验），然后在沙美特罗常规治疗1周后进行第二次特异性支气管激发试验（Salm-2），或者先接受单剂量安慰剂（Plac-1），然后进行1周的安慰剂常规治疗（Plac-2）。每位受试者以随机顺序进行两种治疗。每次在最后一次吸入药物1小时后进行过敏原激发试验，当达到与先前筛查过敏原激发试验相同的激发剂量过敏原时停止试验。与Salm-2、Plac-1、Plac-2相比，Salm-1中吸入过敏原后第一小时FEV1的最大下降幅度和曲线下面积显著更低（最大FEV1下降百分比，中位数[范围]：4%[0至9]），而Salm-2、Plac-1、Plac-2分别为24%[13至38]、31%[19至50]、30%[6至44]，p<0.001）；Salm-2、Plac-1和Plac-2之间无差异。在Salm-1中，所有受试者均受到EAR的保护，而在Salm-2中只有2名受试者表现出部分保护作用。总之，在沙美特罗常规治疗1周后，单剂量沙美特罗对过敏原诱导的EAR的保护作用丧失。该机制的临床相关性仍有待阐明。
