Kidney J C, Boulet L P, Hargreave F E, Deschesnes F, Swystun V A, O'Byrne P M, Choudry N, Morris M M, Jennings B, Andersson N, Andreasson A, Cockcroft D W
Asthma Research Group, McMaster University, Hamilton, Ontario, Canada.
J Allergy Clin Immunol. 1997 Jul;100(1):65-70. doi: 10.1016/s0091-6749(97)70196-9.
Inhaled corticosteroids are the most commonly used antiinflammatory agents for asthma. There is no simple way to compare objectively the relative potency of inhaled corticosteroids. The allergen-induced late asthmatic response (LAR) can be suppressed by a single dose of inhaled corticosteroid.
This study was undertaken to evaluate LAR as a model for the determination of the relative potency of single doses of inhaled corticosteroids.
We compared doses of 200 and 800 microg of a highly active inhaled corticosteroid (budesonide) with placebo and a marginally active investigational inhaled corticosteroid (D5159). Ten atopic patients with asthma completed a randomized, double-blind, double-dummy, multicenter, four-way, crossover trial. A standardized allergen challenge with the identical dose of allergen was performed 10 minutes after each of four blinded, single-dose treatments: 200 microg of budesonide, 800 microg of budesonide, 8 mg of D5159, and placebo, all administered from Turbuhaler. The LAR was recorded as the maximum percent fall in FEV1 between 4 and 7 hours, and the allergen-induced increase in methacholine airway responsiveness at 24 hours was recorded as the A log PC20 from the day before to the day after allergen challenge.
There were no significant differences in the early asthmatic responses during the 4 days; the mean maximum percent in FEV1 fall ranged between 19.5% and 22%. D5159 produced a slight inhibition of the LAR with maximum percent fall in FEV1 recorded as 28.8% +/- 5.0% for D5159 versus 34.1% +/- 4.8% for placebo (p < 0.05). There was a greater reduction recorded after administration of the two doses of budesonide. The mean LAR was 15.1% +/- 3.8% for 200 microg of budesonide and 11.2% +/- 2.3% for 800 microg of budesonide (p < 0.01 compared with placebo and D5159). The two doses of budesonide were not statistically different. Airway responsiveness to methacholine increased by 1.07 doubling doses 24 hours after allergen challenge. This increased airway responsiveness was slightly, but not significantly, reduced by the three active treatments (0.6 to 0.91 doubling doses).
The allergen-induced LAR model was able to differentiate a single dose of an active inhaled corticosteroid from placebo and a highly potent inhaled corticosteroid from a weak inhaled corticosteroid. The model did not differentiate between 2 fourfold doses of the highly active inhaled corticosteroid (at the doses used in this study), neither for the fall in FEV1 nor for the increase in airway hyperresponsiveness.
吸入性糖皮质激素是治疗哮喘最常用的抗炎药物。目前尚无简单方法可客观比较吸入性糖皮质激素的相对效价。单次剂量的吸入性糖皮质激素可抑制变应原诱发的迟发性哮喘反应（LAR）。
本研究旨在评估将LAR作为测定单次剂量吸入性糖皮质激素相对效价模型的可行性。
我们将高活性吸入性糖皮质激素（布地奈德）的200 μg和800 μg剂量与安慰剂以及活性稍低的研究用吸入性糖皮质激素（D5159）进行比较。10名患有哮喘的特应性患者完成了一项随机、双盲、双模拟、多中心、四组交叉试验。在四次盲法单剂量治疗（20 μg布地奈德、800 μg布地奈德、8 mg D5159和安慰剂，均通过都保装置给药）中的每一次治疗后10分钟，使用相同剂量的变应原进行标准化变应原激发试验。将LAR记录为4至7小时内第一秒用力呼气容积（FEV1）的最大下降百分比，并将变应原激发24小时后乙酰甲胆碱气道反应性的增加记录为变应原激发前后的A log PC20。
4天内的早期哮喘反应无显著差异；FEV1下降的平均最大百分比在19.5%至22%之间。D5159对LAR有轻微抑制作用，D5159记录的FEV1最大下降百分比为28.8%±5.0%，而安慰剂为34.1%±4.8%（p < 0.05）。给予两剂布地奈德后记录到更大程度的降低。200 μg布地奈德的平均LAR为15.1%±3.8%，800 μg布地奈德的平均LAR为11.2%±2.3%（与安慰剂和D5159相比，p < 0.01）。两剂布地奈德在统计学上无差异。变应原激发24小时后，气道对乙酰甲胆碱的反应性增加了1.07倍剂量。三种活性治疗（0.6至0.91倍剂量）使这种气道反应性增加略有降低，但不显著。
变应原诱发的LAR模型能够区分活性吸入性糖皮质激素的单次剂量与安慰剂，以及高效吸入性糖皮质激素与低效吸入性糖皮质激素。该模型在本研究使用的剂量下，无法区分高活性吸入性糖皮质激素的两个四倍剂量在FEV1下降或气道高反应性增加方面的差异。
