Restoring epithelial health in epithelial-driven disease through an early treat-to-target approach: improving patient care towards clinical remission.

The structure and function of the airway epithelium are central in protecting against harmful environmental insults and conserving respiratory health; however, epithelial dysfunction can contribute to airway disease. Epithelial health represents a state of equilibrium where the airway epithelial barrier, immune activity and mucociliary dynamics work in concert to maintain tissue integrity and prevent inflammation. An invited Epithelial Science Expert Group met in London in March 2025 to discuss the current understanding of epithelial health in the airways and ways in which epithelial health may be restored in upper and lower inflammatory airway disease. This review summarises the key concepts raised during the meeting. The group discussed the benefits and drawbacks of currently available biomarkers of respiratory epithelial disruption, including mucus plugs, ventilation defects, mucin glycoproteins, cilia beat frequency, tight junction proteins and inflammatory biomarkers. These discussions highlighted a need for biomarkers with the ability to directly assess epithelial function to improve the understanding of epithelial-driven airway disease. Approaches to restore epithelial health were also reviewed, focusing on normalisation of mucin production, restoration of epithelial tight junctions, improvement of the epithelial microbiome, and stem cell therapy, all of which show clinical promise. Attendees highlighted the need for a united airways approach to respiratory disease management, involving multidisciplinary, cross-speciality care. Finally, the trajectory of respiratory epithelial injury and repair over time was explored, focusing on the role of a treat-to-target approach, and early intervention to restore epithelial health and achieve clinical remission in patients with epithelial-driven inflammatory airway disease.