Aerosolized xylitol for ventilator-associated pneumonia

描述（由申请人提供）： 在这个指导性的以患者为导向的研究职业发展奖中，Lakshmi Durairaj寻求获得重症监护室临床试验的专业知识，特别强调预防呼吸机相关肺炎。该奖项将支持Durairaj博士发展成为一名独立的研究人员和一名有成就的临床科学家。Joseph Zabner和James Torner博士将担任主要导师，以确保成功的职业发展。该提案的重点是研究一种新干预措施（即木糖醇，一种5碳糖）预防呼吸机相关肺炎（呼吸机患者中常见的医院感染）的有效性。Durairaj博士完成了临床流行病学的教学培训，其中还包括统计方法和伦理学课程，并获得了流行病学硕士学位。职业发展的具体领域包括临床试验特定统计方法的进一步培训，干预性试验各个阶段的设计，数据收集方法，统计分析和结果解释以及计划未来在重症监护室的研究。 人类的呼吸道被一层薄薄的液体覆盖，其中含有许多在低盐浓度下更有效的抗菌肽。气管定植是呼吸机相关性肺炎发病机制中的重要步骤，呼吸机相关性肺炎是重症监护病房死亡率、住院时间和费用增加的重要原因。木糖醇是一种不可吸收的渗透剂，可降低气道表面液体的盐浓度，并有可能减少呼吸道定植和感染。Durairaj博士将评估木糖醇的气道滞留时间，其在一组机械通气患者中减少气管定植的有效性，并以随机、双盲、对照的方式进行预防这种肺炎的初步安全性研究。在该奖项即将结束时，她将提交一份有竞争力的R-01提案，研究木糖醇预防呼吸机相关肺炎。Durairaj博士将与她所在机构的临床研究、免疫学、肺部和重症监护医学以及传染病专家进行交流。这种智力丰富的环境将有助于促进职业发展，在整个奖项期间提供充分的批判性审查机会。导师和机构都高度致力于Durairaj博士的学术成功。

DESCRIPTION (provided by applicant): In this mentored patient-oriented research career development award, Lakshmi Durairaj seeks to gain expertise in clinical trials in the intensive care unit with particular emphasis on the prevention of ventilator associated pneumonia. This award will support the development of Dr. Durairaj into an independent researcher and an accomplished clinician-scientist. Drs. Joseph Zabner and James Torner will assume responsibility as the primary mentors to ensure a successful career development. The focus of this proposal is to study the effectiveness of a new intervention namely xylitol, a 5-carbon sugar, for the prevention of ventilator-associated pneumonia, a common nosocomial infection among ventilated patients. Dr. Durairaj has completed her didactic training in clinical epidemiology which also included classes in statistical methods and ethics and has a Master's degree in Epidemiology. Specific areas of career development include further training in statistical methods specific for clinical trials, design of various phases of interventional trials, data collection methods, statistical analysis and interpretation of results and planning future studies in the intensive care unit. Human airways are lined by a thin layer of liquid, which contains many antimicrobial peptides which are more potent in lower salt concentrations. Tracheal colonization is an important step in the pathogenesis of ventilator-associated pneumonia, which is an important cause of increased mortality, length of stay, and cost in the intensive care unit. Xylitol is a non-absorbable osmolyte which lowers the salt concentration of airway surface liquid and has the potential to decrease respiratory tract colonization and infection. For this proposal, Dr. Durairaj will assess airway retention time of xylitol, its effectiveness in decreasing tracheal colonization in a group of mechanically ventilated patients, and conduct a pilot safety study for prevention of this pneumonia in a randomized, double-blinded, controlled fashion. Near the termination of this award, she will submit a competitive R-01 proposal to study xylitol for prevention of ventilator-associated pneumonia. Dr. Durairaj will interface with experts in clinical research, immunology, pulmonary and critical care medicine and infectious diseases at her institution. This intellectually rich environment will help foster the career development, providing ample opportunity for critical review throughout the period of this award. Both the mentor and the institution are highly committed to Dr. Durairaj's academic success.