Airway Surface Liquid

Airway cross-sections have the nominal anatomy shown in Fig. 5.16. Airway surface liquid (AST), primarily composed of mucus gel and water, surrounds the airway lumen with a thickness thought to vary from 5 to 10 mm. AST lies on the apical surface of airway epithelial cells (mostly columnar ciliated epithelium). This layer of cells, roughly two to three cells thick in proximal airways and eventually thinning to a single cell thickness in distal airways, rests along a basement membrane on its basal surface. Connective tissue (collagen fibers, basement membranes, elastin, and water) lies between the basement membrane and airway smooth muscle. Edema occurs when the volume of water within the connective tissue increases considerably. Interspersed within the smooth muscle are respiratory supply vessels (capillaries, arteriovenous anastomoses), nerves, and lymphatic vessels. 

Robinson, N. P, Kyle, H., Webbeg S. E., and Widdicombe, J. G. (1989). Electrolyte and other chemical concentrations in tracheal airway surface liquid and mucus. /. Appl. Physiol. 66, 2129-2135. 

Airway surface liquid (ASL) A mixture of periciliary fluid and submucosal... 

Epiphase Airway surface liquid gel layer composed of mucins in the form... 

Airway surface liquid (ASL) is the very thin fluid layer (<7 (llM) maintained at the apical membrane of airway epithelia. ASL thickness is maintained by a tight control of fluid reabsorption and/or secretion, mediated by sodium and/or chloride channels. 

Figure 1 Estimated concentrations of liposomally encapsulated peptide (CM3) in the airway surface liquid (ASL) immediately after completion of nebulization for various simulated subject ages, mucus production rates, and tracheal mucous velocities. Generation 0 corresponds to the trachea, while the terminal bronchioles are generation 14. (From Ref. 1, with permission.)...

Lange CF, Hancock REW, Samuel J, Finlay WH. In vitro aerosol delivery and regional airway surface liquid concentration of a liposomal cationic peptide. J Pharm Sci 2001 40 1647-1657. 

Clunes LA, Davies CM, Coakley RD et al (2012) Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. FASEB J 26(2) 533-545... 

Tarran R, Sabater JR, Clarke TC et al (2013) Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion. Am J Physiol Lung Cell Mol Physiol 304(11) L746-L756... 

Defects in the CFTR decrease the ability of cells to transport Cl in a number of tissues, particularly the pancreas, airway epithelia, and sweat glands. When Cl transport is defective in the pancreas, it leads to decreased HCOj secretion and decreased hydration that leads to thick secretions that block the pancreatic ducts and destruction of the organ. In the lungs, the decreased absorption of Cl ions is thought to increase the absorption of the airway surface liquid thus increasing the viscosity of mucous, decreasing mucociliary... 

Figure 2 Cartoon illustrating the principle of the rat tracheal xenograft model in nu/ nu mice that has been used to investigate the role of normal and cystic fihrosis airway epithelial cells in regulating the production of airway surface liquid, especially hy Goldman and colleagues (38).

Many of the clinical studies into the mechanisms of pulmonary inflammation in cystic fibrosis have centered on determining the presence (or absence) of candidate mediators that may contribute to the pathogenesis of lung inflammation. Studies of both sputum specimens and BAL fluid obtained from adolescents and adults with cystic fibrosis have established that a plethora of pro-inflammatory mediators are present in airway surface liquid in patients with the disease. 

Knowles MR, Robinson JM, Wood RE, Pue CA, Mentz WM, Wager GC, Gatzy JT, Boucher RC. Ion composition of airway surface liquid of patients with cystic fibrosis as compared with normal and disease-control subjects. J Clin Invest 1997 ... 

Hull JW, Skinner W, Robertson C, Phelan P. Elemental content of airway surface liquid from infants with cystic fibrosis. Am J Respir Crit Care Med 1998 157 10. Guggino WB. Cystic fibrosis and the salt controversy. Cell 1999 96 607. Pilewski JM, Frizzell RA. Role of CFTR in airway disease. Physiol Rev 1999 79 S215. 

Coakley RD, Boucher RC. Regulation and functional significance of airway surface liquid pH. JOP J Pancreas (online) 2001 2 294. 

The surface of airway epithelium is covered by airway surface liquid, the physical properties of which are determined by active ions and water transport. Baconnais et al. (1997) developed a technique to study the elemental composition of Na, Mg, P, S, Cl, K and Ca of native airway surface hquid collected in germ-free mice. 

Hirsh, A. J. (2002). "Altering airway surface liquid volume inhalation therapy with amiloride and hyperosmotic agents." Adv Drug DelivRev, 54(11), 1445-62. 

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