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The airway epithelium is a key system within the lung. It acts as a physical barrier to inhaled factors, and can actively remove unwanted microbes and particles from the lung via the mucociliary escalator. On a physiological level, it senses the presence of pathogens and initiates innate immune responses to combat their effects. Hydration of the airways is also controlled by the epithelium. Within the cystic fibrosis (CF) lung, these properties are suboptimal and contribute to the pulmonary manifestations of CF. In this review, we discuss how various host and microbial factors can contribute to airway epithelium dysfunction in the CF lung focusing on mechanisms relating to the mucociliary escalator and protease expression and function. We also explore how alterations in microRNA expression can impact the behavior of the airway epithelium. Notwithstanding the unprecedented benefits that CFTR modulator drugs now provide to the health of CF sufferers, it will be important to delve more deeply into additional mechanisms underpinning CF lung disease such as those illustrated here in an attempt to counteract these aberrant processes and further enhance quality of life for people with CF.

Epithelial damage in the cystic fibrosis lung: the role of host and microbial factors