TY - JOUR T1 - Aclidinium bromide reduces epithelial-mesenchymal transition of human COPD epithelial cells JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P253 AU - Christopher Lambers AU - Katrin Hostettler AU - Nicola Miglino AU - Elisabeth Schuller AU - Michael Roth AU - Lutz-Henning Block Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P253.abstract N2 - Background: Epithelial-mesenchymal transition (EMT) is assumed to contribute to COPD pathogenesis leading to changes in tissue structure.Objective: The effect of aclidinium and formoterol, alone and in combination, on TGF-β1 and cigarette smoke (CS)-induced EMT in primary human epithelial lung cells from patients with stage II COPD (n=6) and non-COPD controls (n=6).Methods: EMT was determined by light microscopy phenotyping of primary cells from lung tissue biopsies. Epithelial cells were defined by knobble-stone shaped and positive staining for E-cadherin; fibroblasts by spindle-shaped cells staining positive for fibronectin. Cells were stimulated over 3 days with either TGF-β1 (5 pg/mL) or with CS-conditioned medium.1Results: TGF-β1 and CS-conditioned medium induced rapid loss of epithelial cell characteristics both in shape and for E-cadherin expression. Within 48 hours >85% of epithelial cells transitioned into fibroblast-like and fibronectin positive cells. Pre-incubation (30 min) with either aclidinium or formoterol (both: 10-11-10-8 M) alone reduced EMT in COPD epithelial cells by 10% and 22%, respectively, but not in cells obtained from non-COPD (control) patients. The drug's combined effect was dose dependent and significantly synergistic on TGF-β1 and CS-induced EMT than the drugs alone.Conclusion: The combination of aclidinium and formoterol has a greater effect on reducing EMT in human epithelial cells compared with either drug alone.Clinical implication: Adding aclidinium, formoterol, or a combination of aclidinium and formoterol to COPD therapy may reduce EMT and thereby slow down the progression of COPD.1Miglino et al. Eur Respir J 2012;39:705-711. ER -