The airway epithelium made up of ciliated cells and goblet cells forming a tight barrier to the outside world. Inset: In a healthy airway epithelium, goblet cells secrete mucin proteins that are incorporated into a thick gel that coats the luminal side of airways and is propelled out of the lung by the beating of cell-surface cilia. In asthma and other airway disease, this mucociliary defense mechanism does not function as effectively and mucus can become trapped and form mucus plugs. Four general mechanisms of mucus dysfunction have been described, including the following: (a) mucus dehydration leading to collapse of the periciliary brush mucus layer, (b) excess production of mucins such as Muc5AC, (c) abnormal tethering of mucus strands to the goblet cell surface, and (d) mucus crosslinking during inflammation. In the presence of eosinophilic airway inflammation, eosinophil peroxidase (EPX), together with other oxidant molecules, can crosslink mucus strands, leading to a more viscous gel that is difficult to expel. These mechanisms likely contribute to the formation of mucus plugs in subjects with eosinophilic asthma. AEC, airway epithelial cell.