Background : Asthma is a chronic inflammatory condition of the airways and patients sensitized to airborne fungi such as Aspergillus fumigatus have more severe asthma. Thickening of the bronchial subepithelial layer is a contributing factor to asthma severity for which no current treatment exists. Airway epithelium acts as an initial defence barrier to inhaled spores, orchestrating an inflammatory response and contributing to subepithelial fibrosis. Objective: We aimed to analyse the production of pro-fibrogenic factors by airway epithelium in response to A fumigatus, in order to propose novel anti-fibrotic strategies for fungal-induced asthma. Methods: We assessed the induction of key pro-fibrogenic factors, TGF-β1, TGF-β2, periostin and endothelin-1, by human airway epithelial cells and in mice exposed to A fumigatus spores or secreted fungal factors. Results: Aspergillus fumigatus specifically caused production of endothelin-1 (1.5pg/ml rising to 3.5pg/ml) by epithelial cells in vitro but not any of the other pro-fibrogenic factors assessed. A fumigatus also induced endothelin-1 in murine lungs (2pg/ml rising to 7pg/ml), associated with extensive inflammation and airway remodelling (peribronchiolar matrix staining rising from 1% to 6%). Using BQ-123 a selective endothelin-1 receptor antagonist in A. fumigatus exposed mice, we observed a reduction in lung lavage inflammatory cells (240X104 to 130 X104) and prevented the induction of airway remodelling. Conclusion: Our findings are consistent with the hypothesis that elevated endothelin-1 levels contribute to subepithelial thickening and highlight this factor as a possible therapeutic target for difficult-to-treat fungal-induced asthma.