Airway Surface Liquid

In this issue of The Journal, Jayaraman and colleagues (2001) describe a novel technique to measure the osmo-lality of airway surface liquid (ASL) using fluorophore-encapsulated liposomes. As in a recent paper reporting measurements of ASL depth, salt concentration, and pH (Jayaraman et al., 2001), this group has once again exploited fluorescence microscopy in an innovative fashion to avoid the shortcomings of the traditional methods of harvesting ASL and analyzing its composition. As reported , ASL osmolality in the mouse was found to be 330 Ϯ 36 mOsM (comparable to that of plasma), and no difference was found between wild-type and CF knockout mice. In addition to providing the beginning of a clear picture of ASL composition under normal conditions , these studies may have important implications for the pathogenesis of cystic fibrosis (CF) lung disease. The use of fluorescent techniques to infer the composition of ASL is a tremendous leap forward in technology , avoiding for the first time the pitfalls associated with techniques based on harvesting ASL or on in situ measurements. The mainstay of ASL studies over the years has been the application of filter paper to the sur-This technique depends on the capillarity generated by the paper fibers, which act as a myriad of high energy capillaries in parallel. The filter paper technique is quite efficient at collecting ASL. Indeed, it may be too effective, generating a sufficiently high driving force to result in the movement of macromolecules from the submucosal surface to the airway lumen (Erjefält and Persson, 1990). Measurements of ASL harvested with this technique have consistently shown [K ϩ ] values substantially above plasma, suggesting the possibility of epithelial damage. Indeed, in our hands, ASL harvested using polyethylene capil-laries (Cowley et al., 1997, 2000), which generate much less force than filter paper, consistently yield [K ϩ ] lower than those found with filter paper. Nevertheless, the polyethylene approach is likely also to generate artefacts because it involves direct contact of the sampling probe with the epithelium. In addition, because of the hydrophobicity of polyethylene, this technique may bias the collection to samples of ASL with a surface tension below the critical surface tension of polyethyl-ene (Landry et al., 2000). Other approaches, such as salt-sensitive electrodes (Caldwell et al., 2000) and electron probe X-ray crystallography (Baconnais et al., 1998), similarly suffer from potential artefacts related to distortion of the epithelium or the ASL itself. The …