Adrenal suppression by inhaled corticosteroids in patients with asthma: A systematic review and quantitative analysis

Background: Inhaled corticosteroids used for treating persistent asthma can suppress adrenal cortisol secretion. This inhibition of endogenous cortisol secretion is an important marker of systemic steroid activity. Although meta-analyses have demonstrated a dose-dependent suppression of cortisol by inhaled corticosteroids, regardless of inhaler type, the impact of novel freon-free inhaled corticosteroid preparations has not been reviewed. Objective: The aim of this study was to synthesize all currently available studies on novel inhaled corticosteroid preparations, including ciclesonide, beclomethasone dipropionate, budesonide, and fluticasone propionate. In particular, we aimed to compare the effect of ciclesonide on cortisol suppression with other existing preparations. Methods: We carried out a systematic review of the medical data bases on cortisol suppression in patients due to inhaled corticosteroids. A multivariate regression model was used to determine dose-dependent relationships between each inhaled corticosteroid and cortisol suppression with respect to age, type of inhaler, and study design. Results: From analysis of 64 studies identified in the review, the strongest dose-response urinary cortisol suppression was observed in patients treated with beclomethasone (8.4% per 100 mu g; p = 0.029), followed by fluticasone (3.2% per 100 mu g; p < 0.001), and budesonide (3.1% per 100 mu g; p = 0.001). No significant urinary cortisol suppression was associated with ciclesonide treatment (1.8% per 100 mu g; p = 0.267). Although ciclesonide did not affect cortisol levels, this appeared to be due to its unique pharmacokinetic properties rather than the use of a novel formulation. Conclusion: Our findings indicated that the introduction of novel freon-free delivery technologies for inhaled corticosteroids had not eliminated adverse adrenal suppression of cortisol secretion.