COPD epithelial phenotype shows partial reversibility in long-term primary epithelial ALI-cultures

The bronchial epithelium in chronic obstructive pulmonary disease (COPD) displays hyperplastic goblet- and basal cells, decreased ciliated cells and epithelial-to-mesenchymal transition (EMT) features. Whether these features are irreversible is incompletely understood. We aimed to delineate the plasticity of the abnormal broncho-epithelial phenotype in COPD. Methods: The airway epithelium (AE) reconstituted in air-liquid interface (ALI) cultures of human primary broncho-epithelial cells from COPD (vs controls), recapitulating the abnormal phenotype observed in situ, was assessed up to 10 weeks for functional (transepithelial electric resistance (TER)), inflammatory (IL-8/CXCL-8 and IL-1α production) and differentiation features including EMT (fibronectin, vimentin). Results: COPD AE show a persistent decrease in TER versus controls (p<0.0001). In contrast, the initial increases of vimentin and fibronectin production in COPD (fibronectin at 1 week, 62.69±16.2 versus 7.81±1.79 ng/ml in controls, p