Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na+] and pH but elevated viscosity

Fluid and macromolecule secretion by submucosal glands in mammalian airways is believed to be important in normal airway physiology and in the pathoph ysiology of cystic fibrosis (Cf), An in situ fluorescence method was applie d to measure the ionic composition and viscosity of freshly secreted fluid from airway glands. Fragments of human large airways obtained at the time o f lung transplantation were mounted in a humidified perfusion chamber and t he mucosal surface was covered by a thin layer of oil. Individual droplets of secreted fluid were microinjected with fluorescent indicators for measur ement of [Na+], [Cl-], and pH by ratio imaging fluorescence microscopy and viscosity by fluorescence recovery after photobleaching. After carbachol st imulation, 0.1-0.5 mul of fluid accumulated in spherical droplets at gland orifices in approximate to3-5 min. In gland fluid from normal human airways , [Na+] was 94 +/- 8 mM, [Cl-] was 92 +/- 12 mM, and pH was 6.97 +/- 0.06 ( SE, n = 7 humans, more than five glands studied per sample). Apparent fluid viscosity was 2.7 +/- 0.3-fold greater than that of saline. Neither [Na+] nor pH differed in gland fluid from CF airways, but viscosity was significa ntly elevated by approximate to2-fold compared to normal airways. These res ults represent the first direct measurements of ionic composition and visco sity in uncontaminated human gland secretions and indicate similar [Na+], [ Cl-], and pH to that in the airway surf ace liquid. The elevated gland flui d viscosity in CF may be an important factor promoting bacterial colonizati on and airway disease.