Pathophysiology of Aerodigestive Reflexes in Infants

婴儿呼吸消化反射的病理生理学

• 批准号: 8456057
• 负责人: Sudarshan R Jadcherla
• 金额: $ 42.38万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8456057
• 关键词: Acids; Admission activity; Age; Benchmarking; Blinded; Cessation of life; Clinical; Complex; Data; Deglutition; Development; Diagnosis; Diagnostic; Diagnostic tests; Dose; Economic Burden; Economics; Enteral; Esophageal; Event; Failure; Feeding Methods; Feeding Patterns; Feeds; Functional disorder; Funding; Fundoplication; Future; Gastroesophageal reflux disease; Gastrostomy; Goals; Health; Hospitalization; Hour; Human; Infant; Infant Development; Inferior esophageal sphincter structure; Investigation; Knowledge; Lateral; Length of Stay; Manometry; Manuscripts; Methods; Mission; Morbidity - disease rate; Motor; Movement; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal Intensive Care Units; Omeprazole; Oral; Outcome; Parents; Patients; Peer Review; Peristalsis; Physicians; Positioning Attribute; Posture; Prevalence; Preventive; Public Health; Qualifying; Quality of life; Questionnaires; Randomized; Recurrence; Reflex action; Reflux; Relative Risks; Relaxation; Research; Sensory; Severities; Supine Position; Symptoms; Term Birth; Testing; Therapeutic; Therapeutic Intervention; Translating; Ultrasonography; United States National Institutes of Health; Upper Esophageal Sphincter; Validation; Work; base; control trial; cost; design; effectiveness trial; electric impedance; evidence base; feeding; high risk infant; improved; indexing; innovation; neonate; novel; nutrition; premature; prospective; respiratory; stem; success; tool; trial comparing; two-arm study

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.

描述（由申请人提供）：胃食管反流疾病（GERD）及其麻烦的并发症构成了对新生儿重症监护病房中加入的婴儿的安全喂养和防气道保护策略的严重诊断和管理挑战；从而导致长时间住院时间，复发住院和死亡。 GERD经常通过标准不足来诊断，而GERD疗法的相对风险，益处和适应症尚不清楚。知识的显着差距在理解复杂的因果或适应性的机械化保护反射机制中，涉及婴儿的GERD。长期的目标是通过更好地了解机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，营养和婴儿的发育。当前的目标是进行一项前瞻性单中心随机盲人对照试验，以比较我们创新的喂养策略捆绑包与标准喂养方法的短期影响。中心统一的假设是，我们的创新喂养策略捆绑包将修改负责食管清除和气道保护的几种气化反射的重叠功能，以改善这些患者的临床结果。该假设是根据我们在R01资金期间的先前工作提出的。该提案的理由是通过了解与婴儿喂养方法相关的气化反射的传入效率关系的整合来最大程度地减少GERD的病态。在强大的初步数据的指导下，将通过追求两个具体目的来检验该假设：1）标准喂养方法的临床结果与创新的喂养策略捆绑包进行比较，以及2）确定成功或未能治疗的成功的病理生理机制。在AIM-1下，我们将检验以下假设：创新的喂养策略捆绑包在实现口服喂养成功和减少婴儿征询义务征用症状的症状评分方面更有效。在AIM-2下，我们将通过利用我们的诊断工具来检验假设并验证初步数据的结果，以识别两个研究臂之间的差异，这些研究臂在空气消化反射，食管清除机制，吞噬的吞咽神经运动标记和pH-Impedance-Mypedance-MINSTOM INDICES方面。该方法具有创新性，因为我们使用最先进的方法，包括多模式食管感官挑衅方法，视频管理方法，pH势态方法，症状指数，Glottal超声检查和创新的喂养策略。拟议的研究很重要，因为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原理，以优化GERD的疗法。预计将在婴儿中开发GERD的预防和治疗策略的新基准，这将对婴儿和父母的生活质量产生积极影响。