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Mechanisms and clinical implications of glucocorticoid resistance in asthma

Author
Ian M Adcock, FSB
Section Editor
Bruce S Bochner, MD
Deputy Editor
Helen Hollingsworth, MD

INTRODUCTION

Glucocorticoids (GCs) have potent antiinflammatory actions, and are the most effective anti-inflammatory agents in the treatment of asthma. It is now clear that asthma is a syndrome with many distinct and overlapping phenotypes with severe GC-refractory asthma at one end of a spectrum of GC responsiveness [1]. Patients with GC-refractory asthma account for a large percentage of the overall costs for asthma worldwide, but also provide unique insights into the mechanisms of GC action. These patients should not be confused with those who either do not take their anti-inflammatory medication or patients who do not have access to the correct treatments [2,3].

The European Respiratory Society/American Thoracic Society (ERS/ATS) and the Global Initiative for Asthma (GINA) guidelines provide pragmatic approaches to treatment strategy for severe asthma based on patient stratification and expert opinion [1,2,4].

The basic mechanisms of glucocorticoid resistance in asthma and clinical implications for diagnosis and management of severe asthma will be reviewed here. GC use in GC-sensitive asthma and GC resistance in other disease states are reviewed separately. (See "An overview of asthma management" and "Unusual causes of adrenal insufficiency".)

DEFINITION

Glucocorticoid (GC) responsiveness represents a continuous spectrum, with GC-resistant individuals falling at one end of a unimodal distribution. Patients with severe asthma who are poorly responsive to high doses of GCs and are without confounding factors (table 1) have been termed GC-resistant [1]. A larger subset of patients with asthma that is poorly-controlled despite optimal treatment or who experience worsening of asthma control during GC withdrawal have severe asthma and are considered relatively GC-insensitive [1]. High doses of GCs usually indicate a daily dose of 1000 microg or more of inhaled fluticasone propionate or 2000 microg or more of triamcinolone, the equivalent (table 2).

MECHANISMS OF GLUCOCORTICOID ACTION

GCs exert their effects by influencing target cell transcriptional regulation and protein synthesis (figure 1).

                   

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Literature review current through: Nov 2016. | This topic last updated: Mon Jun 06 00:00:00 GMT+00:00 2016.
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