From triggers to asthma: a narrative review on epithelium dysfunction.

It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.