The respiratory epithelium provides a physical, functional, and immunologic barrier to protect the host from the potential harming effects of inhaled environmental particles and to guarantee maintenance of a healthy state of the host. When compromised, activation of immune/inflammatory responses against exogenous allergens, microbial substances, and pollutants might occur, rendering individuals prone to develop chronic inflammation as seen in allergic rhinitis, chronic rhinosinusitis, and asthma. The airway epithelium in asthma and upper airway diseases is dysfunctional due to disturbed tight junction formation. By putting the epithelial barrier to the forefront of the pathophysiology of airway inflammation, different approaches to diagnose and target epithelial barrier defects are currently being developed. Using single-cell transcriptomics, novel epithelial cell types are being unraveled that might play a role in chronicity of respiratory diseases. We here review and discuss the current understandings of epithelial barrier defects in type 2–driven chronic inflammation of the upper and lower airways, the estimated contribution of these novel identified epithelial cells to disease, and the current clinical challenges in relation to diagnosis and treatment of allergic rhinitis, chronic rhinosinusitis, and asthma.

呼吸道上皮提供了物理，功能和免疫屏障，可保护宿主免受吸入的环境颗粒的潜在伤害，并确保维持宿主的健康状态。当受到损害时，可能会发生针对外源性过敏原，微生物物质和污染物的免疫/炎症反应的激活，从而使个体易于发生慢性炎症，如在变应性鼻炎，慢性鼻-鼻窦炎和哮喘中所见。哮喘和上呼吸道疾病的气道上皮功能异常，是由于紧密连接形成受到干扰。通过将上皮屏障置于气道炎症的病理生理学的最前沿，目前正在开发用于诊断和靶向上皮屏障缺陷的不同方法。使用单细胞转录组学，新型上皮细胞类型正在研究中，可能在呼吸系统疾病的慢性病中起作用。我们在这里回顾和讨论当前对2型上呼吸道和下呼吸道慢性炎症中上皮屏障缺损的认识，这些新发现的上皮细胞对疾病的估计贡献以及与临床诊断和治疗有关的当前临床挑战过敏性鼻炎，慢性鼻鼻窦炎和哮喘。