Eosinophilic bronchitis in asthma: A model for establishing dose-response and relative potency of inhaled corticosteroids - 17/08/11
, Richard Leigh, MBChB, PhD a, Lata Jayaram, MBChB a, Charlie H. Goldsmith, PhD b, Krishnan Parameswaran, MD, PhD a, Frederick E. Hargreave, MD a
Reprint requests: Margaret M.Kelly, MBChB, Immunology Research Group, Institute of Infection, Immunity and Inflammation, University of Calgary, Room HSC 1863, 3330 Hospital Drive NW, Calgary Alberta T2N 4N1, Canada.Hamilton, Ontario, Canada
Abstract |
Background |
Newer generations and formulations of inhaled corticosteroids have necessitated the development of 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 μg/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 μg/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.
Conclusion |
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.
Clinical implications |
Future clinical studies based on this model will allow clinicians to make informed decisions regarding the relative potencies of different inhaled corticosteroids.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, inhaled corticosteroids, fluticasone propionate, relative potency, sputum eosinophils
Abbreviations used : ECP, eNO, FP, ICS
Plan
| Supported by the Therapeutics Products Programme of Health Canada, Ottawa, Canada. GlaxoSmithKline, Canada, supplied all study medications but provided no other financial support. Disclosure of potential conflict of interest: R. Leigh received honoraria from Altana, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Pfizer, and Sanofi-Aventis Pharmaceuticals. K. Parameswaran has received research grants from GlaxoSmithKline, AstraZeneca, and Sepracor, and has received honoraria from Merck Frost, AstraZeneca, and GlaxoSmithKline. F. Hargreave is on the GlaxoSmithKline advisory board. The rest of the authors have declared that they have no conflict of interest. |
Vol 117 - N° 5
P. 989-994 - mai 2006 Retour au numéro
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