Authors: Zhe ZhouSuckow Julia Duerr Matthias Hagner Raman Agrawal Marcus A Mall
Publish Date: 2017/01/20
Volume: 367, Issue: 3, Pages: 537-550
Abstract
Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis CF and primary ciliary dyskinesia as well as common lung diseases such as asthma and chronic obstructive pulmonary disease COPD which have emerged as a leading cause of morbidity and mortality worldwide However the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood The generation of mice with airwayspecific overexpression of epithelial Na+ channels ENaC exhibiting airway surface dehydration mucus hyperconcentration impaired mucociliary clearance MCC and mucus plugging led to a model of mucoobstructive lung disease that shares key features of CF and COPD In this review we summarize recent progress in the understanding of causes of impaired MCC and in vivo consequences of airway mucus obstruction that can be inferred from studies in βENaCoverexpressing mice These studies confirm that mucus hyperconcentration on airway surfaces plays a critical role in the pathophysiology of impaired MCC mucus adhesion and airway plugging that cause airflow obstruction and provide a nidus for bacterial infection In addition these studies support the emerging concept that excess airway mucus per se probably via several mechanisms including hypoxic epithelial necrosis retention of inhaled irritants or allergens and potential immunomodulatory effects is a potent trigger of chronic airway inflammation and associated lung damage even in the absence of bacterial infection Finally these studies suggest that improvement of mucus clearance may be a promising therapeutic strategy for a spectrum of mucoobstructive lung diseases
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