Airway Mucus Function and Dysfunction

The lungs are remarkably resistant to environmental injury, despite continuous exposure to pathogens, particles, and toxic chemicals in inhaled air.Their resistance depends on a highly effective defense provided by airway mucus, 1-7 an extracellular gel in which water and mucins (heavily glycosylated proteins) are the most important components.Airway mucus traps inhaled toxins and transports them out of the lungs by means of ciliary beating and cough (Fig. 1).2][3][4] This review examines the normal formation and clearance of airway mucus, the formation of pathologic mucus, the failure of mucus clearance that results in symptoms and abnormal lung function, and the therapy of mucus dysfunction. STRUCTURE AND FUNCTION OF THE NORMAL AIRWAYEpithelial surfaces in contact with the outside environment are protected by mechanical barriers (e.g., keratinized skin) and chemical barriers (e.g., gastric acid).2][3][4][5][6][7] Mucus layers vary widely in composition and structure; for example, they are thick and adherent to the epithelium in the gut, but thin and mobile in the airway. SURFACE EPITHELIAL CELLSThe surface epithelium of intrapulmonary airways is composed of two principal cell types -ciliated and secretory (Fig. 2).These cells are present in similar numbers and form a mosaic.Secretory cells have been further divided into subtypes based on their microscopical appearance (e.g., Clara, goblet, and serous cells).1][12][13][14] Therefore, it is simplest to refer to them generically as "secretory cells."Besides mucins, secretory cells release a variety of antimicrobial molecules (e.g., defensins, lysozyme, and IgA), immunomodulatory molecules