In the respiratory tract, mucus is a critical component of the innate host defense system. On the airway epithelial cell surface, the sticky gel layer traps particles and the sol layer, which is predominantly water, contacts the surface of ciliated cells and permits moving of the gel out of the lower airways like an escalator so that it can ultimately be cleared by coughing or swallowing. Mucus also contains antibacterial agents to aid in its defense function. Pathogens and harmless proteins we inhale are thus removed from the respiratory tract and have a limited encounter with other immune components. In the bronchial airways, mucus is produced by surface epithelial cells with secretory features and a classical goblet shape, called goblet cells. Goblet cells produce mucins that are complexed with water in secretory granules and are released into the airway lumen. In the large airways, mucus is also produced by mucous glands. Under basal conditions, the columnar epithelial surface comprises a small percentage of goblet cells and a majority of ciliated cells. This structure provides adequate mucus to capture particles and remove them in the huge volumes of air we breathe. After infection or toxic exposure, the airway epithelium upregulates its mucous secretory ability, and we cough and bring up sputum. Subsequently, the airway epithelium recovers and returns to its normal state, goblet cells disappear, and coughing abates.
Mucous hypersecretion is a hallmark of chronic airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, and goblet cell hyperplasia and persistence are characteristic pathologic features. In asthmatics, 20–25% of airway epithelial cells are goblet cells, even in mild disease (1
). All of these diseases have distinct etiologies and different inflammatory responses that drive mucous hypersecretion. In asthma, inflammation appears to be mediated by allergen-specific Th2 cells, leading to eosinophilia, while in COPD, the inflammatory response is neutrophilic and may be induced by infection or components in cigarette smoke (3
). Controlling inflammation is at the root of treatment through the use of corticosteroids and/or antibiotics, yet despite therapy, airway obstruction remains the cause of morbidity and mortality. Mucous secretions in the airways in asthma and COPD appear to be a major cause of airway obstruction, ventilation-perfusion mismatching, and hypoxemia, leading to wheezing and dyspnea (4
). Can and should we be doing more to control mucus?