Epithelial mesenchymal transition (EMT) related changes in small airways of smokers and patients with COPD

Abstract

<b>Aim:</b> We previously provided evidence that EMT is active in patients with chronic airflow limitation. We now illustrate EMT changes in a wider demographic patient group consisting of COPD current and ex-smokers (COPD-CS, COPD-ES), small airway disease (SAD) and normal lung function smokers (NLFS) compared to healthy controls (HC). <b>Method:</b> Immunohistochemical staining was done in small airways (SA) resected tissue from COPD-CS and -ES, SAD, NLFS and HC, for mesenchymal protein S100A4 and Vimentin, and epithelial marker E-cadherin. S100A4 and Vimentin +ive cells were counted in SA epithelium and reticular basement membrane (Rbm) per mm of Rbm while E-cadherin was analysed as percentage. All tissue analysis was done with Image-ProPlus 7.0. <b>Result:</b> E-cadherin markedly decreased across all pathological groups with minimal intergroup variability compared to HC (p&lt;0.01). SA epithelium was significantly positive for both Vimentin and S100A4 in NLFS (p&lt;0.01), SAD (p&lt;0.001) and COPD groups (p&lt;0.001) than HC, albeit COPD-ES tended back to normal levels. Rbm Vimentin +ive cells showed a similar trend to epithelium across all pathological groups (p&lt;0.01), however, such changes where only observed for NLFS and COPD-ES regarding S100A4 (p&lt;0.04). Epithelial Vimentin and S100A4 (r=-0.45, p&lt;0.001; r=-0.51, p&lt;0.001), and Rbm Vimentin and S100A4 (r=-0.48, p&lt;0.001; r=-0.36, p&lt;0.01) expression negatively correlated with E-cadherin expression. <b>Conclusions:</b> EMT is an active process in the SA of smokers and patients with COPD potentially contributing to SA fibrosis and obliteration seen in these patients. This is the first study to show such changes in well phenotyped individuals.