title: Mechanisms of glucocorticoid action and insensitivity in airways disease.
abstract: Glucocorticoids are the mainstay for the treatment of chronic inflammatory diseases including asthma and chronic obstructive pulmonary disease (COPD). However, it has been recognized that glucocorticoids do not work well in certain patient populations suggesting reduced sensitivity. The ultimate biologic responses to glucocorticoids are determined by not only the concentration of glucocorticoids but also the differences between individuals in glucocorticoid sensitivity, which is influenced by multiple factors. Studies are emerging to understand these mechanisms in detail, which would help in increasing glucocorticoid sensitivity in patients with chronic airways disease. This review aims to highlight both classical and emerging concepts of the anti-inflammatory mechanisms of glucocorticoids and also review some novel strategies to overcome steroid insensitivity in airways disease.
authors.affiliation: Airway Disease, National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Boardman
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: L
authors.initials: L
authors.lastname: Chachi
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Gavrila
authors.affiliation: Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: C R
authors.initials: CR
authors.lastname: Keenan
authors.affiliation: Airway Disease, National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: M M
authors.initials: MM
authors.lastname: Perry
authors.affiliation: Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Y C
authors.initials: YC
authors.lastname: Xia
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Meurs
authors.affiliation: Department of Physiology and Pharmacology, Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, 4C46 HRIC, 3280 Hospital Dr NW, Calgary, AB, Canada T2N 4N1. Electronic address: pawan.sharma@jefferson.edu.
authors.forename: P
authors.initials: P
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D012140:Respiratory Tract Diseases / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid
keywords: Asthma; Chronic airway diseases; Combination therapy; Glucocorticoid; Inflammation; Steroid resistance