Why do some asthma patients respond poorly to glucocorticoid therapy?

Henderson, I., Caiazzo, E., McSharry, C., Guzik, T. J. and Maffia, P. (2020) Why do some asthma patients respond poorly to glucocorticoid therapy? Pharmacological Research, 160, 105189. (doi: 10.1016/j.phrs.2020.105189) (PMID:32911071) (PMCID:PMC7672256)

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Glucocorticosteroids are the first-line therapy for controlling airway inflammation in asthma. They bind intracellular glucocorticoid receptors to trigger increased expression of anti-inflammatory genes and suppression of pro-inflammatory gene activation in asthmatic airways. In the majority of asthma patients, inhaled glucocorticoids are clinically efficacious, improving lung function and preventing exacerbations. However, 5–10 % of the asthmatic population respond poorly to high dose inhaled and then systemic glucocorticoids. These patients form a category of severe asthma associated with poor quality of life, increased morbidity and mortality, and constitutes a major societal and health care burden. Inadequate therapeutic responses to glucocorticoid treatment is also reported in other inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease; however, asthma represents the most studied steroid-refractory disease. Several cellular and molecular events underlying glucocorticoid resistance in asthma have been identified involving abnormalities of glucocorticoid receptor signaling pathways. These events have been strongly related to immunological dysregulation, genetic, and environmental factors such as cigarette smoking or respiratory infections. A better understanding of the multiple mechanisms associated with glucocorticoid insensitivity in asthma phenotypes could improve quality of life for people with asthma but would also provide transferrable knowledge for other inflammatory diseases. In this review, we provide an update on the molecular mechanisms behind steroid-refractory asthma. Additionally, we discuss some therapeutic options for treating those asthmatic patients who respond poorly to glucocorticoid therapy.

Item Type:Articles
Additional Information:Our work is funded by the British Heart Foundation grants PG/19/84/34771 and RE/13/5/30177; the European Commission Marie Skłodowska-Curie Individual Fellowships 661369; the Engineering and Physical Sciences Research Council (EPSRC) grant EP/L014165/1; the European Research Council (InflammaTENSION; project Identifier: 726318); the Wellcome Trust grant 204820/Z/16/Z; and the University of Glasgow Scottish Funding Council and the Global Challenges Research Fund. C.McS. is funded by the BPF medical research trust. E.C. is funded by the Italian Ministry of University and Research (MIUR) PRIN 2017 (2017NKB2N4_003).
Glasgow Author(s) Enlighten ID:Maffia, Professor Pasquale and Guzik, Professor Tomasz and CAIAZZO, Miss ELISABETTA and McSharry, Dr Charles
Authors: Henderson, I., Caiazzo, E., McSharry, C., Guzik, T. J., and Maffia, P.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Pharmacological Research
ISSN (Online):1096-1186
Published Online:08 September 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Pharmacological Research 160:105189
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
308639Defining the individual and integrated roles of inflammatory chemokine receptors (iCCRs) in atherosclerosisPasquale MaffiaBritish Heart Foundation (BHF)PG/19/84/34771CAMS - Cardiovascular Science
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
190739In Situ Nanoparticle Assemblies for Healthcare Diagnostics and Therapy. Reference: 130479Pasquale MaffiaEngineering and Physical Sciences Research Council (EPSRC)EP/L014165/1III - Immunology
300798A study of the roles of the immune and inflammatory systems in hypertensionTomasz GuzikEuropean Research Council (ERC)726318CAMS - Cardiovascular Science
173707Institutional Strategic Support Fund (2016)Anna DominiczakWellcome Trust (WELLCOTR)204820/Z/16/ZInstitute of Cardiovascular & Medical Sciences
171799NanoMATePasquale MaffiaEuropean Commission (EC)661369III - Immunology