Safety assessment of inhaled xylitol in mice and healthy volunteers
Safety assessment of inhaled xylitol in mice and healthy volunteers
复制标题
DOI：
10.1186/1465-9921-5-13
复制
发表时间：
2004-09-16
影响因子：
5.8
通讯作者：
Zabner, J
中科院分区：
文献类型：
--
作者：
Durairaj, L;Launspach, J;Zabner, J
背景：木糖醇是一种5碳糖，可降低呼吸道表面盐分浓度，从而增强天然免疫功能。我们测试了雾化吸入等渗木糖醇在小鼠和人类志愿者中的安全性和耐受性。方法：这是一项前瞻性队列研究，C57BL/6小鼠在动物实验室进行，健康志愿者在大学医院临床研究中心进行。小鼠接受基线乙酰甲胆碱挑战，暴露于雾化生理盐水或木糖醇(5%溶液)150分钟，然后进行后续乙酰甲胆碱挑战。在卵蛋白致敏和吸入激发诱导嗜酸性气道炎症后，重复暴露生理盐水和木糖醇。正常人志愿者暴露在雾化生理盐水(10ml)和木糖醇中，在基线和吸入1、5和10ml后进行肺活量测定。在基线和最后一次暴露后测量血清渗透压和电解质。在基线、最后一次暴露后和暴露后五天进行呼吸系统症状问卷调查。在另一组正常志愿者中，雾化吸入木糖醇20分钟和3小时后进行支气管肺泡灌洗(BAL)，以检测炎症标志物的水平。结果：在幼龄小鼠中，吸入木糖醇后乙酰甲胆碱反应性与吸入生理盐水相比没有变化(p=0.49)。暴露于木糖醇后，抗原攻击组小鼠的脑白质分泌没有显著增加(p=0.38)。在幼鼠和抗原攻击小鼠中，暴露于木糖醇后的呼吸道细胞反应没有变化。在正常志愿者中，与基线和生理盐水暴露相比，木糖醇暴露后FEV1没有变化(p=0.19)。安全实验室的数值也没有变化。报告的唯一不良反应是一半的受试者在接触10毫升木糖醇期间鼻塞，在暴露完成后很快就消失了。正常志愿者吸入木糖醇后BAL细胞因子水平均低于检测限值。结论：雾化吸入等渗木糖醇对幼鼠和特应性小鼠以及健康志愿者均有良好的耐受性。
Background: Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers.Methods: This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline ( 10 ml) and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers.Results: In naive mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response after xylitol exposure in naive and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were below the detection limits after xylitol exposure in normal volunteers.Conclusions: Inhalation of aerosolized iso-osmotic xylitol was well-tolerated by naive and atopic mice, and by healthy human volunteers.