The airway epithelium: an orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma

Asthma is a disease of heterogeneous pathology, typically characterised by excessive inflammatory and bronchoconstrictor responses to the environment. The clinical expression of the disease is a consequence of the interaction between environmental factors and host factors over time, including genetic susceptibility, immune dysregulation and airway remodelling. As a critical interface between the host and the environment, the airway epithelium plays an important role in maintaining homeostasis in the face of environmental challenges. Disruption of epithelial integrity is a key factor contributing to multiple processes underlying asthma pathology. In this review, we first discuss the unmet need in asthma management and provide an overview of the structure and function of the airway epithelium. We then focus on key pathophysiological changes that occur in the airway epithelium, including epithelial barrier disruption, immune hyperreactivity, remodelling, mucus hypersecretion and mucus plugging, highlighting how these processes manifest clinically and how they might be targeted by current and novel therapeutics.