SAFETY OF AEROSOLIZED XYLITOL IN SUBJECTS WITH CYSTIC FIBROSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human airway surface is covered with a thin layer of liquid that contains many antimicrobial substances that forms the local host defense system. The antimicrobial activity of this airway surface liquid (ASL) depends on its salt concentration; decrease in ASL salt concentration enhances the activity of this innate defense system. Xylitol is a 5-carbon sugar that lowers the salt concentration of airway surface, because it is an impermeable osmolyte. Hence, it can be potentially useful in preventing hospital-acquired upper and lower respiratory colonization and infection and in the prevention of infection in patients with cystic fibrosis. Aerosolized hypotonic solutions such as water and hypertonic saline have been shown to cause bronchospasm in asthmatic subjects leading to the generalized use of isotonic saline solutions for aerosolization. Hypertonic saline has been used as a bronchoprovocative agent for diagnosis of asthma. Hypertonic solutions have been used in patients with cystic fibrosis to increase mucociliary clearance with good tolerability and safety profile. In a recent pilot study, we showed that aerosolized iso-osmotic xylitol is well-tolerated by normal volunteers. In this study we propose to test the safety and tolerability of aerosolized xylitol in iso-osmolar concentration in subjects with cystic fibrosis.