Inhaled corticosteroids are being recommended for use in asthma treatment both more frequently and at higher doses than previously. Since corticosteroids have multiple potential adverse systemic effects, it is essential to be able to compare the different available inhaled steroids and delivery systems with respect to both systemic effects and efficacy as an asthma treatment. While several inhaled steroids (with differing in vitro potencies and pharmacokinetic characteristics) and inhaled delivery systems are presently available, and others expected to be introduced in coming years, in vivo systemic effects data comparing these inhaled steroids and delivery systems are lacking. In this study we propose an experimental paradigm in which inhaled steroids and delivery systems are characterized in terms of systemic effects so that equi-systemic doses can be subsequently compared in future efficacy trials. Adrenal suppression will be used as the primary index of systemic absorption. We acknowledge that growth in children and connective tissue parameters are important indicators of systemic absorption, but due to the slow rate of change in these outcome measures, they do not lend themselves to rapid evaluation. We therefore propose to use plasma cortisol profiles (determined over time) which are a sensitive and reproducible indicator of basal adrenal function as our index of systemic absorption. Urine cortisol excretion will be a secondary measure of adrenal suppression. Markers of bone remodelling which are sensitive to steroids, specifically serum osteocalcin and urinary N-telopeptide, will also be incorporated as secondary indices of systemic absorption and effect.
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