TY - JOUR T1 - Increased myofibroblasts in the small airways and relation to remodelling and functional changes in smokers and COPD patients: potential role of epithelial-mesenchymal transition (EMT) JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00876-2020 SP - 00876-2020 AU - Mathew Suji Eapen AU - Wenying Lu AU - Tillie L. Hackett AU - Gurpreet Kaur Singhera AU - Malik Q. Mahmood AU - Ashutosh Hardikar AU - Chris Ward AU - Eugene Haydn Walters AU - Sukhwinder Singh Sohal Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2021/03/11/23120541.00876-2020.abstract N2 - Introduction Previous reports showed epithelial mesenchymal transition (EMT) as an active process that contributes to small airway (SA) fibrotic pathology. Myofibroblasts are highly active pro-fibrotic cells that secrete excessive and altered extracellular matrix (ECM). Here we relate SA myofibroblast presence with airway remodelling, physiology and EMT activity in smokers and COPD patients.Methods Lung resections from non-smoker controls (NC), normal lung function smokers (NLFS), COPD current (CS) and ex-smokers (ES) were stained with anti-human αSMA, collagen 1, and fibronectin. αSMA+ive cells were computed in reticular basement membrane (Rbm), lamina propria (LP), and adventitia and presented per mm of Rbm and mm2 of LP. Collagen-1 and fibronectin are presented as a percentage change from normal. All analysis including airway thickness were measured using Image-pro-plus 7.0.Results We found an increase in sub-epithelial LP (especially) and adventitia thickness in all pathological groups compared to NC. Increases in αSMA+ive myofibroblasts were observed in sub-epithelial Rbm, LP, and adventitia in both the smoker and COPD groups compared to NCs. Further, the increase in the myofibroblast population in the LP was strongly associated with decrease in lung function, LP thickening, increase in ECM protein deposition, and finally EMT activity in epithelial cells.Conclusions This is the first systematic characterisation of small airway myofibroblasts in COPD based on their localisation, with statistically significant correlations between them and other pan-airway structural, lung function, and ECM protein changes. Finally, we suggest that EMT may be involved in such changes.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Eapen has nothing to disclose.Conflict of interest: Dr. Lu has nothing to disclose.Conflict of interest: Dr. Hackett has nothing to disclose.Conflict of interest: Dr. Singhera has nothing to disclose.Conflict of interest: Dr. Mahmood has nothing to disclose.Conflict of interest: Dr. Hardikar has nothing to disclose.Conflict of interest: Dr. Ward has nothing to disclose.Conflict of interest: Dr. Walters has nothing to disclose.Conflict of interest: Dr. Sohal reports personal fees from Chiesi, outside the submitted work. ER -