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Corticosteroids

  • Chapter
Pharmacology and Therapeutics of Asthma and COPD

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 161))

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Abstract

Corticosteroids are by far the most effective treatments currently available for the treatment of asthma. Inhaled corticosteroids have revolutionised the management of asthma and have been the most important advance in therapy over the last 30 years. Initially, inhaled corticosteroids were introduced to reduce the requirement for oral corticosteroids in patients with more severe disease, but now their use has extended to patients with much milder disease, including children. This is in part because it is recognised that airway inflammation is present even in patients with mild asthma when they may have no symptoms, and in part because of their great safety at low doses. The molecular mechanisms of corticosteroids are now much better understood, and it is now known that corticosteroids suppress the increased expression of multiple inflammatory genes that are over-expressed in asthmatic airways, accounting for their clinical efficacy. The mechanism whereby corticosteroids switch off multiple inflammatory genes appears to involve reversal of acetylation of core histones, particularly through the recruitment of histone deacetylases. Inhaled corticosteroids are now recommended as first-line treatment for all patients (adults and children) with persistent asthma. The early use of inhaled steroids in asthma has been shown to reduce symptoms, improve the quality of life of patients, prevent exacerbations and reduce airway hyperresponsiveness. There is increasing evidence that early use of inhaled corticosteroids may reduce the irreversible changes in airway function that occur in some patients with asthma. Several studies now suggest that inhaled corticosteroids have a relatively flat dose-response curve and that most benefit is achieved at rather low doses. Increasing the dose of inhaled corticosteroids has less benefit than adding another class of drug, such as an inhaled long-acting β 2-agonist or theophylline in patients not controlled on low doses of inhaled corticosteroids. Systemic side effects are not an important issue when low doses of inhaled corticosteroids are used. There is no evidence for growth suppression in children treated with low doses of inhaled corticosteroids and no evidence for osteoporosis in adults. Some patients with asthma are resistant or relatively resistant to the anti-inflammatory effects of corticosteroids, and several molecular mechanisms for this steroid resistance have been elucidated. Patients with chronic obstructive pulmonary disease (COPD) show a poor response to corticosteroids and there may be an active resistance, due to impaired function of histone deacetylases. Several new corticosteroids are in development with the view of improving the therapeutic ratio.

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  1. Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse St, London, SW3 6LY, UK

    P. J. Barnes

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  1. Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, 5th Floor, Hodgkin Building, Guy’s Campus, SE1 1UL, London, UK

    Clive P. Page

  2. National Heart & Lung Institute, Department of Thoracic Medicine, Imperial College, Dovehouse Street, SW3 6LY, London, UK

    Peter J. Barnes

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Barnes, P.J. (2004). Corticosteroids. In: Page, C.P., Barnes, P.J. (eds) Pharmacology and Therapeutics of Asthma and COPD. Handbook of Experimental Pharmacology, vol 161. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-09264-4_4

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