Airway epithelial-mesenchymal-transition and vascular changes in patients with asthma-COPD overlap (ACO)

<bold>Introduction:</bold> ACO is a term that describes patients exhibiting clinical features of both asthma and COPD. Epithelial-mesenchymal-transition (EMT) and vascularity are related to airway remodelling in COPD and asthma patients; however, they remain unexplored in ACO. This study aims to evaluate EMT and vascular changes in airway tissue from ACO patients. <bold>Methods:</bold> Large airway endobronchial biopsies from patients with ACO (12) were compared to asthma (14), COPD (22), normal lung function smokers (NLFS; 12) and healthy non-smoking subjects (HC; 10). Immunohistochemical staining was performed for EMT markers (E- and N-cadherin, Vimentin, S100A4) and Collagen IV for vessels. The positive expression of each EMT marker and Collagen IV positive vessels in the epithelium (EP), reticular basement membrane (Rbm), and lamina propria (LP) were assessed. We also evaluated the degree of Rbm fragmentation. <bold>Results:</bold> In the EP, ACO showed a significantly reduced percentage of E-cadherin expression compared to HC (p<0.01), with no change for N-cadherin expression. We observed the most substantial Rbm fragmentation in ACO, which is a key tissue structural marker of EMT and was significantly higher than HC (p<0.01). Both Vimentin and S100A4 positive basal cells tended to be higher in ACO than in HC. In the Rbm, S100A4 positive cells were markedly elevated in ACO (p<0.05) compared to HC. The number of vessels in the Rbm were higher in ACO (p<0.05) compared to HC but lower in the LP (p<0.01). <bold>Conclusion:</bold> These findings suggest the presence of an active EMT process with prominent and contrasting changes in Rbm and LP vascularity in ACO, potentially contributing to severe airway remodelling seen in this cohort.