Impact of non-acid reflux on respiratory diseases in children

描述(由申请人提供)： 本次K23职业发展奖的候选人是一位专攻食道生理学的儿科胃肠病专家。候选人的长期职业目标是在儿科胃肠病领域拥有学术研究生涯，通过研究与反流相关的呼吸道疾病来改善儿童的健康。该奖项要实现的短期职业目标包括：(1)获得高级统计学和流行病学方面的正式培训；(2)获得更多使用多通道管腔内阻抗(pH-MII)的专业知识，这是一种新兴的胃食道反流(GER)测量工具；(3)加深候选人对GER与呼吸道疾病之间关系的知识；以及(4)获得所需的宝贵指导，以确保候选人在成为R01资助的临床研究人员方面取得进步。 候选人的主要导师大卫·克里斯汀尼博士在肺病学和流行病学方面有很强的背景，这是他研究毒素和呼吸道疾病之间因果关系的基础。候选人的多学科指导团队还包括在儿科肺病学、耳鼻喉科、胃肠病学和统计学方面具有专业知识的教职员工。培训活动包括高级统计学和流行病学的课程作业；参加临床研究会议；以及导师的教学指导。 这项应用概述了第一项儿科研究，以确定非酸反流在呼吸系统疾病中的作用，使用两项新技术：pH-MII和带有阻抗的食道测压。通过对儿童的横断面和队列研究，候选人将确定(1)非酸反流与呼吸道症状之间的时间关系；(2)非酸反流与反流相关呼吸道疾病标记物之间的关联强度和剂量-反应关系；(3)非酸反流与呼吸道疾病严重程度之间的关联强度和剂量-反应关系。这项研究的发现可能会导致从酸性反流到非酸性反流作为呼吸道疾病的一个原因的典型转变。这项研究的发现还可能导致改进诊断和治疗呼吸道疾病的战略，这些疾病已经在儿童中占了很大的比例。

DESCRIPTION (provided by applicant): The candidate for this K23 Career Development Award is a pediatric gastroenterologist who specializes in esophageal physiology. The candidate's long-term career goal is to have an academic research career in pediatric gastroenterology that improves the health of children through the study of reflux-related respiratory diseases. Short-term career goals to be achieved with this award include: (1) to obtain formal training in advanced statistics and epidemiology; (2) to gain additional expertise in the use of multi-channel intraluminal impedance (pH-MII), an emerging tool for measuring gastroesophageal reflux (GER); (3) to deepen the candidate's knowledge of the relationship between GER and respiratory disease; and (4) to acquire the valuable mentorship required to ensure the candidate's progress toward becoming a R01-funded clinical investigator. The candidate's primary mentor, Dr. David Christiani, has a strong background in pulmonology and epidemiology that forms the basis for his studies of the cause-and-effect relationships between toxins and respiratory disease. The candidate's multidisciplinary mentorship team also includes faculty members with expertise in pediatric pulmonology, otolaryngology, gastroenterology, and statistics. Training activities include coursework in advanced statistics and epidemiology; participation in clinical research conferences; and didactic instruction from mentors. This application outlines the first pediatric study to determine the role of non-acid reflux in respiratory disease using two novel technologies: pH-MII and esophageal manometry with impedance. Through cross-sectional and cohort studies of children, the candidate will determine (1) the temporal relationship between non-acid reflux and respiratory symptoms; (2) the strength of association and the dose-response relationship between non-acid reflux and markers of reflux-related respiratory disease; and (3) the strength of association and the dose-response relationship between non-acid reflux and the severity of respiratory disease. Findings from this research may lead to a paradigmatic shift from acid reflux to non-acid reflux as a cause of respiratory disease. Findings from this study also may lead to improved strategies for diagnosing and treating respiratory diseases, which already account for significant morbidity in children.