In search of the perfect steroid

Background: The use and continued advancement of steroids are fundamental to the treatment of asthma. Objective: To review the development of steroids, specifically inhaled corticosteroids (ICSs), in the treatment of asthma and understand how these agents have been progressively refined to improve therapeutic margins. Methods: Peer-reviewed articles, books, and other publications focusing on the use of steroids in asthma were retrieved using MEDLINE searches and other external sources. Results: Adrenocorticotropic hormone (ACTH) and oral corticosteroids (OCSs) were introduced for the treatment of asthma in the 1950s. However, ACTH is no longer used because of allergic potential and variable response, and the potential systemic adverse events associated with OCSs (eg, osteoporosis, cataracts, growth failure, hypothalamic-pituitary-adrenal axis suppression) has reduced their use. ICSs were subsequently introduced as safer options to OCSs, with improved therapeutic margins. The efficacy and safety of ICSs depend on pharmacokinetic and pharmacodynamic properties (eg, systemic and oral bioavailability, pulmonary deposition, receptor binding, pulmonary residence time, systemic clearance). Manipulation of these properties has led to ICSs with progressively improved therapeutic margins. However, prolonged use of some ICSs at high doses can still be associated with certain systemic and oropharyngeal adverse events. Newer ICSs with optimized pharmacokinetic and pharmacodynamic profiles may offer further advances with regard to the safety of ICS treatment. Conclusions: Asthma therapy and management have improved greatly since the mid-20th century. However, further progress is needed to improve treatment options and help improve therapeutic outcomes for all patients with asthma.