Bronchoscopic assessment of airway retention time of aerosolized xylitol

Abstract

Background: Human airway surface liquid (ASL) has abundant antimicrobial peptides whose potency increases as the salt concentration decreases. Xylitol is a 5-carbon sugar that has the ability to lower ASL salt concentration, potentially enhancing innate immunity. Xylitol was detected for 8 hours in the ASL after application in airway epithelium in vitro. We tested the airway retention time of aerosolized iso-osmotic xylitol in healthy volunteers.

Methods: After a screening spirometry, volunteers received 10 ml of nebulized 5% xylitol. Bronchoscopy was done at 20 minutes (n = 6), 90 minutes (n = 6), and 3 hours (n = 5) after nebulization and ASL was collected using microsampling probes, followed by bronchoalveolar lavage (BAL). Xylitol concentration was measured by nuclear magnetic resonance spectroscopy and corrected for dilution using urea concentration.

Results: All subjects tolerated nebulization and bronchoscopy well. Mean ASL volume recovered from the probes was 49 +/- 23 microl. The mean ASL xylitol concentration at 20, 90, and 180 minutes was 1.6 +/- 1.9 microg/microl, 0.6 +/- 0.6 microg/microl, and 0.1 +/- 0.1 microg/microl, respectively. Corresponding BAL concentration corrected for dilution was consistently lower at all time points. The terminal half-life of aerosolized xylitol obtained by the probes was 45 minutes with a mean residence time of 65 minutes in ASL. Corresponding BAL values were 36 and 50 minutes, respectively.

Conclusion: After a single dose nebulization, xylitol was detected in ASL for 3 hours, which was shorter than our in vitro measurement. The microsampling probe performed superior to BAL when sampling bronchial ASL.

Figure 1

In vitro half-life of xylitol in human airway epithelia. Panel A. Transmission electron micrograph of perfluorocarbon/OsO4 fixed human airway epithelia grown on a semi-permeable membrane filter. The vertical bar in the left upper quadrant shows ASL height which measured 5 μm. Panel B. Xylitol concentration in the basolateral surface quantitated by NMR after addition to the apical surface.

Figure 2

ASL volume recovered by BMS probe over time. * p = 0.03.

Figure 3

Semi-logarithmic plot of concentration of xylitol in human ASL plotted against time from the start of nebulization. The closed circles represent BMS probe data and open circles represent BAL data.

Figure 4

Simulated xylitol concentration versus time profile for the BMS probe and BAL methods. The solid line represents the simulated curve using population parameters (Table 1) obtained for the BMS probe method and the dashed line represents the simulated curve for the BAL method.