Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 117, Issue 5, Pages 989-994Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2006.01.045
Keywords
asthma; inhaled corticosteroids; fluticasone propionate; relative potency; sputum eosinophils
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Background: Newer generations and formulations of inhaled corticosteroids have necessitated the development or a clinically relevant model to compare their clinical potency. Objective: We evaluated whether sputum eosinophil counts could demonstrate a dose-response to inhaled corticosteroids, and compared the response with other inflammatory markers. Methods: Fourteen steroid-naive patients with asthma with an initial sputum eosinophilia of >= 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 mu g/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. Results: 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 mu g/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.
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