Holz Olaf, Tal-Singer Ruth, Kanniess Frank, Simpson Kathy J, Gibson Anthony, Vessey Rupert S J, Janicki Stanislawa, Magnussen Helgo, Jörres Rudolf A, Richter Kai
Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Wöhrendamm 80, D-22927 Grosshansdorf, Germany.
J Clin Pharmacol. 2005 May;45(5):498-503. doi: 10.1177/0091270004273527.
This study aimed to test the utility of the ozone challenge model for profiling novel compounds designed to reduce airway inflammation. The authors used a randomized, double-dummy, double-blind, placebo-controlled 3-period crossover design alternating single orally inhaled doses of fluticasone propionate (inhaled corticosteroids, 2 mg), oral prednisolone (oral corticosteroids, 50 mg), or matched placebo. At a 2-week interval, 18 healthy ozone responders (>10% increase in sputum neutrophils) underwent a 3-hour ozone (250 ppb)/intermittent exercise challenge starting 1 hour after drug treatment. Airway inflammation was assessed at 2 hours (breath condensate) and 3 hours (induced sputum) after ozone challenge. Compared to placebo, pretreatment with inhaled corticosteroids or oral corticosteroids resulted in a significant reduction (mean [95% confidence interval]) of sputum neutrophils by 62% (35%, 77%) and 64% (39%, 79%) and of sputum supernatant myeloperoxidase by 55% (41%, 66%) and 42% (25%, 56%), respectively. The authors conclude that an optimized ozone challenge model (including ozone responders and ensuring adequate drug levels during exposure) may be useful for testing novel anti-inflammatory compounds in early development.
本研究旨在测试臭氧激发模型对于筛选旨在减轻气道炎症的新型化合物的效用。作者采用了随机、双模拟、双盲、安慰剂对照的3期交叉设计，交替单次口服吸入丙酸氟替卡松（吸入性糖皮质激素，2毫克）、口服泼尼松龙（口服糖皮质激素，50毫克）或匹配的安慰剂。每隔2周，18名健康的臭氧反应者（痰中性粒细胞增加>10%）在药物治疗1小时后接受3小时的臭氧（250 ppb）/间歇性运动激发。在臭氧激发后2小时（呼出气冷凝液）和3小时（诱导痰）评估气道炎症。与安慰剂相比，吸入性糖皮质激素或口服糖皮质激素预处理可使痰中性粒细胞分别显著减少62%（35%，77%）和64%（39%，79%），痰上清液髓过氧化物酶分别显著减少55%（41%，66%）和42%（25%，56%）。作者得出结论，优化的臭氧激发模型（包括臭氧反应者并确保暴露期间有足够的药物水平）可能有助于在早期开发中测试新型抗炎化合物。
