Kelly Margaret M, Leigh Richard, Jayaram Lata, Goldsmith Charlie H, Parameswaran Krishnan, Hargreave Frederick E
Airways Research Group, Firestone Institute for Respiratory Health, Hamilton, Canada.
J Allergy Clin Immunol. 2006 May;117(5):989-94. doi: 10.1016/j.jaci.2006.01.045. Epub 2006 Mar 31.
Newer generations and formulations of inhaled corticosteroids have necessitated the development of a clinically relevant model to compare their clinical potency.
We evaluated whether sputum eosinophil counts could demonstrate a dose-response to inhaled corticosteroids, and compared the response with other inflammatory markers.
Fourteen steroid-naive patients with asthma with an initial sputum eosinophilia of > or = 2.5% entered a 6-week sequential, placebo-controlled, patient-blinded, cumulative dose-response study. After 7 days of placebo, they received incremental doses of fluticasone propionate (FP), 50, 100, 200, and 400 microg/d, each for 7 days. Measurements were made of sputum and blood eosinophils, exhaled nitric oxide, spirometry, airway responsiveness to methacholine (methacholine PC20), and symptom scores before and after each dose.
Sputum eosinophils and exhaled nitric oxide were extremely sensitive to the effects of FP, and exhibited significant dose-dependent reductions of 99.4% and 99.8 parts per billion, respectively, where each variable was expressed per 100 microg/d FP. This compared with a 0.5 doubling dose increase of airway responsiveness to methacholine and a 0.3 decrease in symptom scores. Airway responsiveness to methacholine was the only variable that increased throughout the study.
These results suggest that the model of eosinophilic bronchitis could be used to compare the effect of cumulative doses of an inhaled corticosteroid delivered by different types of delivery systems or preparations using a relatively small number of patients.
Future clinical studies based on this model will allow clinicians to make informed decisions regarding the relative potencies of different inhaled corticosteroids.
新一代吸入性糖皮质激素及其剂型的出现，使得开发一种具有临床相关性的模型以比较其临床效力成为必要。
我们评估痰液嗜酸性粒细胞计数是否能显示对吸入性糖皮质激素的剂量反应，并将该反应与其他炎症标志物进行比较。
14名初诊痰液嗜酸性粒细胞增多（≥2.5%）且未使用过类固醇的哮喘患者进入一项为期6周的序贯、安慰剂对照、患者盲法、累积剂量反应研究。在接受7天安慰剂治疗后，他们接受递增剂量的丙酸氟替卡松（FP），分别为50、100、200和400μg/d，每种剂量治疗7天。在每次给药前后测量痰液和血液嗜酸性粒细胞、呼出一氧化氮、肺功能、气道对乙酰甲胆碱的反应性（乙酰甲胆碱PC20）以及症状评分。
痰液嗜酸性粒细胞和呼出一氧化氮对FP的作用极为敏感，分别显示出显著的剂量依赖性降低，每100μg/d FP时分别降低99.4%和99.8 ppb。相比之下，气道对乙酰甲胆碱的反应性增加了0.5倍剂量，症状评分降低了0.3。气道对乙酰甲胆碱的反应性是整个研究中唯一增加的变量。
这些结果表明，嗜酸性粒细胞性支气管炎模型可用于比较不同类型给药系统或制剂递送的吸入性糖皮质激素累积剂量的效果，且所需患者数量相对较少。
基于该模型的未来临床研究将使临床医生能够就不同吸入性糖皮质激素的相对效力做出明智决策。
