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Epithelial cells lining the airways and the respiratory compartment may, and certainly when exposed to an inflammatory milieu, display an altered functioning, which could contribute to pathophysiology of inflammatory lung/airway disease. In the present review paper, several issues that were discussed at an earlier European Respiratory Society Research Seminar on conditions that affect epithelial functioning have been recapitulated and updated. These and future studies should improve understanding of epithelial functioning and may aid recovery from disease.