title: Adrenal suppression by inhaled corticosteroids in patients with asthma: A systematic review and quantitative analysis.
abstract: 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 μg; p = 0.029), followed by fluticasone (3.2% per 100 μg; p < 0.001), and budesonide (3.1% per 100 μg; p = 0.001). No significant urinary cortisol suppression was associated with ciclesonide treatment (1.8% per 100 μg; 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.
  
  
  CONCLUSIONS
  Our findings indicated that the introduction of novel freon-free delivery technologies for inhaled corticosteroids had not eliminated adverse adrenal suppression of cortisol secretion.
authors.affiliation: Department of Immunology, Rheumatology and Allergy, Healthy Aging Research Center, Medical University of Lodz, Lodz, Poland.
authors.forename: Marek L
authors.initials: ML
authors.lastname: Kowalski
authors.forename: Piotr
authors.initials: P
authors.lastname: Wojciechowski
authors.forename: Marta
authors.initials: M
authors.lastname: Dziewonska
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Rys
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D006854:Hydrocortisone