Pathophysiology of Aerodigestive Reflexes in Infants

描述(申请人提供)：胃食道反流病(GERD)及其棘手的并发症对在新生儿重症监护病房疗养的婴儿制定安全喂养和呼吸道保护策略构成严重的诊断和管理挑战；从而导致长时间住院、反复住院和死亡。GERD的诊断标准往往不充分，GERD治疗的相对风险、益处和适应症尚不清楚。在理解婴儿GERD所涉及的复杂的原因或适应性空气消化保护反射机制方面，存在着重大的知识空白。长期目标是通过更好地了解空气消化反射的病理生理学，通过设计简化的个性化治疗范例来改善消化健康、营养和婴儿发育。目前的目标是进行一项前瞻性的单中心随机双盲对照试验，比较我们创新的喂养策略捆绑和标准喂养方法的短期效果。中心统一假设是，我们创新的喂养策略捆绑包将修改几个负责食道清除和呼吸道保护的空气消化反射的重叠功能，以改善这些患者的临床结果。这一假设是基于我们在R01资助期的先前工作提出的。这一建议的基本原理是通过了解与婴儿喂养方法有关的空气消化反射的传入-传出关系的整合，将GERD的发病率降至最低。在强大的初步数据的指导下，这一假说将通过追求两个具体目标来检验：1)比较标准喂养方法和创新喂养策略包的临床结果，以及2)确定两种疗法成功或失败的病理生理机制。在AIM-1下，我们将检验创新喂养策略捆绑在实现口服喂养成功和降低婴儿-GER-问卷修订症状评分方面更有效的假设。在AIM-2下，我们将利用我们的诊断工具验证假设并验证初步数据的结果，以确定两个研究分支在空气消化反射、食道清除机制、吞咽神经运动标志物和pH阻抗症状指数方面的差异。这种方法是创新的，因为我们使用了最先进的方法，包括多模式食道感觉刺激方法、视频测压、pH阻抗方法、症状指数、声门超声检查和创新的喂养策略。这项拟议的研究意义重大，因为所获得的知识将为未来改进GERD治疗方法的多中心有效性试验提供科学和经济依据。预计制定婴儿GERD预防和治疗策略的新基准将对婴儿和父母的生活质量产生积极影响。

DESCRIPTION (provided by applicant): Gastroesophageal reflux disease (GERD) and its troublesome complications constitute serious diagnostic and management challenges to the development of safe feeding and airway protection strategies among infants convalescing in the neonatal intensive care units; thus contributing to prolonged lengths of stay, recurrent hospitalizations, and death. GERD is frequently diagnosed by inadequate criteria, and the relative risks, benefits and indications of GERD therapies are unclear. Significant gaps in knowledge exist in understanding the complex causal or adaptive aerodigestive protective reflex mechanisms implicated in GERD in infants. The long-term goal is to improve digestive health, nutrition, and infant development through the design of simplified personalized treatment paradigms by better understanding the pathophysiology of aerodigestive reflexes. The current objective is to conduct a prospective single center randomized blinded controlled trial comparing the short term effects of our innovative feeding strategy bundle versus standard feeding approach. The central unifying hypothesis is that our innovative feeding strategy bundle will modify the overlapping functions of several aerodigestive reflexes responsible for esophageal clearance and airway protection to improve clinical outcomes in these patients. This hypothesis is formulated based on our prior work during the R01 funding period. The rationale for this proposal is to minimize morbidities from GERD by understanding the integration of afferent-efferent relationships of aerodigestive reflexes in relation to infant feeding approaches. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Comparison of the clinical outcomes of standard feeding approach with the innovative feeding strategy bundle, and 2) Determination of the pathophysiological mechanism of success or failure to either therapy. Under aim-1, we will test the hypothesis that the innovative feeding strategy bundle is more effective in achieving the oral feeding success and decrease in infant-GER-questionnaire-revised symptom scores. Under aim-2, we will test the hypothesis and validate results from the preliminary data by utilizing our diagnostic tools to identify difference between the two study arms in regards to aero-digestive reflexes, esophageal clearance mechanisms, enteric neuromotor markers of swallowing, and pH-impedance-symptom indices. The approach is innovative, in that we use state-of-the-art methods including multimodal esophageal sensory provocation methods, videomanometry, pH-Impedance methods, symptom indices, glottal ultrasonography, and innovative feeding strategy. The proposed research is significant, because knowledge gained will provide the scientific and economic rationale for future multicenter effectiveness trials to refine therapies for GERD. New benchmarks to develop preventative and therapeutic strategies for GERD in infants are anticipated, which will positively impact the quality of life for infants and parents.