Background: Studies examining the effects of inhaled corticosteroids (ICSs) on cortisol suppression show inconsistent results, and there is uncertainty regarding the dose-response relationship between ICSs and cortisol suppression. Objective: To determine, using meta-analysis, the extent of cortisol suppression after administration of clinically relevant ICS doses in adults with asthma. Methods: Database searches (MEDLINE, EMBASE, and The Cochrane Library) using appropriate indexed terms were performed to identify eligible articles for review. Articles reporting the effects of ICSs on cortisol levels in asthmatic adults, measured using the cumulative serum or plasma cortisol, morning serum or plasma cortisol, or cumulative overnight urinary free cortisol method, were identified. All available cortisol measurements were extracted. Cortisol suppression was estimated, and treatment arms were grouped into low-, medium-, and high-dose ranges according to the Global Initiative for Asthma guidelines. A multivariate model was used to determine relationships between ICS dose and cortisol suppression and to explore sources of heterogeneity among trials. Results: Thirty-one studies providing information on 216 measures of cortisol suppression were included in this meta-analysis. Cortisol suppression in the low-, medium-, and high-dose groups were estimated to be 17.92% (95% confidence interval [CI], 11.08%-24.77%), 26.55% (95% CI, 17.29%-35.80%), and 36.31% (95% CI, 26.48%-46.13%), respectively. Conclusions: Statistically significant cortisol suppression was evident at low doses of ICSs and increased with dose. These results support an impact of all ICSs on endogenous cortisol levels and underscore the importance of titrating ICS doses to the minimum required to maintain symptom control.
Annals of Allergy, Asthma and Immunology Vol. 100, Issue 1, p. 23-30