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A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial-mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study

Citation

Sohal, SS and Soltani, A and Reid, D and Ward, C and Wills, KE and Muller, HK and Walters, EH, A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial-mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study, International Journal of COPD, 9, (1) pp. 533-542. ISSN 1178-2005 (2014) [Refereed Article]


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Copyright Statement

Copyright 2014 The Authors-licensed under Creative Commons Attribution–Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/.

DOI: doi:10.2147/COPD.S63911

Abstract

Background: We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma. With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a "proof of concept" study. Methods: Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo). The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation ("hallmark" structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers). Results: Epithelial activation, "clefts/fragmentation" in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance. From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study. Conclusion: Although only a pilot "proof of concept" study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways. A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important. Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD.

Item Details

Item Type:Refereed Article
Keywords:pilot trial, reticular basement membrane, S100A4, EGFR, MMP-9, lung cancer
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Respiratory Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Respiratory System and Diseases (incl. Asthma)
Author:Sohal, SS (Dr Sukhwinder Sohal)
Author:Soltani, A (Dr Amir Soltani Abhari)
Author:Reid, D (Dr David Reid)
Author:Ward, C (Dr Christopher Ward)
Author:Wills, KE (Dr Karen Wills)
Author:Muller, HK (Professor Konrad Muller)
Author:Walters, EH (Professor Haydn Walters)
ID Code:92206
Year Published:2014
Web of Science® Times Cited:36
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-06-10
Last Modified:2017-10-31
Downloads:236 View Download Statistics

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