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Clinical and molecular aspects of glucocorticoid resistant asthma

Authors Chris J Corrigan, Tuck-Kay Loke

Published 15 November 2007 Volume 2007:3(5) Pages 771—787


Chris J Corrigan, Tuck-Kay Loke

Division of Asthma, Allergy and Lung Biology, King’s College London, London, England, UK; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, London, England, UK

Abstract: This paper is an overview of the diagnosis, differential diagnosis and cellular and molecular mechanisms of glucocorticoid resistant asthma. It addresses the clinical definition and rationale for the diagnosis of therapy resistant asthma. It purports that, since glucocorticoid resistant asthmatics are not globally physiologically glucocorticoid resistant, then the phenomenon is most likely acquired, probably in immune cells (and most probably in T cells and monocyte/macrophages), as a result of local inflammatory and environmental influences. The molecular mechanisms which have been uncovered to date which could account for glucocorticoid resistance are discussed, in particular the roles of AP-1 and p38 MAP kinase signaling, the role of the β-isoform of the glucocorticoid receptor and the role of histone proteins and DNA folding. Finally, there are suggestions for clinical management of these patients based on accumulated evidence.

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