Pathophysiology of Aerodigestive Reflexes in Infants

描述（由申请人提供）：胃食管反流病（GERD）及其棘手的并发症对新生儿重症监护病房中康复婴儿的安全喂养和气道保护策略的发展构成了严重的诊断和管理挑战；从而导致住院时间延长、反复住院和死亡。GERD的诊断标准经常不充分，GERD治疗的相对风险、益处和适应症尚不清楚。在理解与婴儿反流病相关的复杂因果或适应性气消化保护反射机制方面存在显著的知识空白。长期目标是通过更好地了解气消化反射的病理生理，设计简化的个性化治疗范例，改善消化系统健康、营养和婴儿发育。目前的目标是进行一项前瞻性单中心随机盲法对照试验，比较我们的创新喂养策略组合与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束将改变负责食管清除和气道保护的几种空气消化反射的重叠功能，以改善这些患者的临床结果。这一假设是根据我们在R01资助期间的前期工作制定的。该建议的基本原理是通过理解与婴儿喂养方法相关的空气消化反射的传入-传出关系的整合，将反流病的发病率降到最低。在强有力的初步数据的指导下，这一假设将通过两个具体目标进行验证：1)比较标准喂养方法与创新喂养策略组合的临床结果；2)确定两种治疗方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包在实现口服喂养成功和降低婴儿ger -问卷修正症状评分方面更有效的假设。在目标2中，我们将通过使用我们的诊断工具来验证假设和初步数据的结果，以确定两个研究组在空气消化反射、食管清除机制、肠内吞咽神经运动标志物和ph阻抗症状指数方面的差异。该方法是创新的，因为我们使用了最先进的方法，包括多模态食管感觉刺激法、视频测压法、ph -阻抗法、症状指数、声门超声检查和创新的喂养策略。拟议的研究意义重大，因为所获得的知识将为未来的多中心有效性试验提供科学和经济依据，以改进反流胃食管反流的治疗方法。预计将有新的基准来制定婴儿反流胃食管反流的预防和治疗策略，这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. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because the pathophysiology based infant feeding practices will overcome the burden of aerodigestive suffering in infants with gastroesophageal reflux disease. The proposed studies will overcome the critical barrier to progress by providing the scientific and economic rationale for the development of safe feeding paradigms in vulnerable infants, and enhances digestive health in infants, all relevant to the mission of NIH (NIDDK).