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  • S89 Epithelial Mesenchymal Transition (EMT) in Chronic Obstructive Pulmonary Disease (COPD) Airways is Attenuated by Inhaled Corticosteroids (ICS)

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Mechanisms of airway injury in COPD
S89 Epithelial Mesenchymal Transition (EMT) in Chronic Obstructive Pulmonary Disease (COPD) Airways is Attenuated by Inhaled Corticosteroids (ICS)
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  1. Sukhwinder Singh Sohal1,
  2. Amir Soltani1,
  3. David Reid2,
  4. Chris Ward3,
  5. Steven Weston1,
  6. Hans Konrad Muller1,
  7. Richard Wood-Baker1,
  8. Eugene Haydn Walters1
  1. 1NHMRC Centre of Research Excellence in Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Australia
  2. 2Iron Metabolism Laboratory, Queensland Institute of Medical Research, Queensland, Australia.
  3. 3Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom

Abstract

Introduction and Objectives We recently reported1, 2 that EMT is active in the airways of COPD patients; in this process epithelial cells change shape and become motile, then digest through the reticular basement membrane (Rbm) which becomes fragmented and transition to a mesenchymal fibroblast-like cell. We also demonstrated that the Rbm is hyper-vascular, a combined picture specifically suggesting active EMT-type-III, which is a dangerous, pre-malignant condition. This may well be the link between COPD and lung cancer. In this study, we have assessed the effects of ICS on markers of EMT in endobronchial biopsies (ebb) in COPD.

Methods A double-blinded, randomised, placebo-controlled study assessed the effects of inhaled fluticasone propionate (FP: 500µg twice daily) on EMT in 34 COPD patients. Ebb were assessed for EMT related Rbm fragmentation (core structural marker) and immunostained for the EMT signatures S100A4 (a fibroblast epitope), matrix-metalloproteinase-9 (MMP-9) and the epithelial activation marker, epidermal growth factor receptor (EGFR).

Results Table 1.

View this table:
Abstract S89 Table 1

Comparison of different indices at baseline and after treatment between the two groups. Data expressed as medians and ranges

Conclusions This is the first study to report the positive effects of ICS on EMT markers in COPD. This may be the mechanistic link between ICS and its reported preventive action against smoking-related lung cancer in COPD.

References

  1. Sohal SS, et al. Respirology 2010, 15(6):930–938.

  2. Sohal SS, et al. Respir Res 2011, 12(1):130.

https://doi.org/10.1136/thoraxjnl-2012-202678.095

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