Low-dose budesonide/formoterol counteracts airway inflammation and improves lung function in COPD

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Title: Low-dose budesonide/formoterol counteracts airway inflammation and improves lung function in COPD
Authors: Hakim, A
Khan, Y
Esteban, I
Meah, S
Miller-Larsson, A
Barnes, PJ
Usmani, OS
Item Type: Journal Article
Abstract: The latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) document recommends new treatment algorithms, with inhaled corticosteroids (ICS) use only in moderate-to-severely symptomatic COPD patients with repeated exacerbations, where the emphasis is to review ICS use and to reduce ICS dosing (1). Indeed, safety concerns of pneumonia (2) with high-dose ICS has further concerted focus upon using appropriate doses of ICS. It is well-established that ICS in combination with long-acting β2-adrenoceptor agonist (LABA) can decrease exacerbations, improve symptoms and increase quality of life in patients with COPD (3-4), but nonetheless, the rationale to consider step-down of ICS is supported by several clinical studies (5). The Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial studied severe COPD patients on therapy with ICS, LAMA and LABA, where stepwise withdrawal of ICS did not lead to an increase in exacerbations compared to continued ICS use (6). Determining the optimal dose of ICS and LABA combination therapy is of great biological and clinical importance in order to address safety concerns associated with high-dose ICS use. There is in vitro evidence to support the clinical practice of using low-dose ICS. Low-dose ICS in combination with LABA enhances corticosteroid function by enhancing glucocorticoid receptor (GR) activity (7) and suppresses the release of inflammatory mediators (8). However, it is unknown whether this observation of enhanced corticosteroid function with low-dose ICS/LABA has a direct effect on airways inflammation and lung function. Our study investigated the cellular function that may be relevant and underpin the clinical approach to lowering the dose of ICS therapy in COPD patients. We compared the single administration of low-dose ICS/LABA combination to high-dose ICS alone and high-dose ICS/LABA on GR activation, molecular markers of AJRCCM as airway inflammation and lung function in COPD patients 2 hours post-treatment. Some of the results of these studies have been previously reported in the form of an abstract (9).
Issue Date: 12-Dec-2018
Date of Acceptance: 6-Dec-2018
URI: http://hdl.handle.net/10044/1/65336
DOI: https://dx.doi.org/10.1164/rccm.201808-1590LE
ISSN: 1073-449X
Publisher: American Thoracic Society
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Copyright Statement: © 2018 American Thoracic Society.
Keywords: 11 Medical And Health Sciences
Respiratory System
Publication Status: Published online
Conference Place: United States
Embargo Date: 2019-12-12
Online Publication Date: 2018-12-12
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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