SAFETY OF AEROSOLIZED XYLITOL IN SUBJECTS WITH CYSTIC FIBROSIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。人体气道表面覆盖着一层薄薄的液体，其中含有许多抗菌物质，形成了局部宿主防御系统。该气道表面液（ASL）的抑菌活性取决于其盐浓度；ASL盐浓度的降低增强了这种先天防御系统的活性。木糖醇是一种降低气道表面盐浓度的5碳糖，因为它是一种不可渗透的渗透物。因此，它在预防医院获得性上、下呼吸道定植和感染以及预防囊性纤维化患者感染方面具有潜在的作用。雾化的低渗溶液，如水和高渗盐水，已被证明会引起哮喘受试者的支气管痉挛，导致普遍使用等渗盐水溶液雾化。高渗盐水已被用作支气管刺激剂诊断哮喘。高渗溶液已用于囊性纤维化患者，以增加粘液纤毛清除率，具有良好的耐受性和安全性。在最近的一项初步研究中，我们发现雾化的等渗透木糖醇在正常志愿者中具有良好的耐受性。在这项研究中，我们建议在囊性纤维化患者中测试等渗透压浓度雾化木糖醇的安全性和耐受性。

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.