92206 Journal Article.pdf (445.66 kB)
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
journal contributionposted on 2023-05-18, 01:23 authored by Sukhwinder SohalSukhwinder Sohal, Soltani, A, Reid, D, Ward, C, Karen WillsKaren Wills, Muller, HK, Eugene WaltersEugene Walters
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.
Publication titleInternational Journal of COPD
Department/SchoolTasmanian School of Medicine
PublisherDove Medical Press Ltd.
Place of publicationUnited Kingdom
Rights statementCopyright 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/.