Pathophysiology of Aerodigestive Reflexes in Infants

婴儿呼吸消化反射的病理生理学

• 批准号: 8289148
• 负责人: Sudarshan R Jadcherla
• 金额: $ 46.66万
• 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/8289148
• 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. 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).

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室中康复期婴儿的安全喂养和气道保护策略的制定构成了严重的诊断和管理挑战;因此导致住院时间延长、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、获益和适应症尚不清楚。在理解与婴儿GERD有关的复杂的因果性或适应性呼吸消化保护性反射机制方面存在重大的知识差距。长期目标是通过更好地了解呼吸消化反射的病理生理学，设计简化的个性化治疗模式，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捆绑与标准喂养方法的短期效果。核心统一假设是，我们的创新喂养策略包将修改负责食道清除和气道保护的几种呼吸消化反射的重叠功能，以改善这些患者的临床结果。该假设是基于我们在R 01资助期间的先前工作制定的。该建议的基本原理是通过了解与婴儿喂养方法相关的呼吸消化反射的传入-传出关系的整合来最大限度地减少GERD的发病率。在强有力的初步数据的指导下，将通过追求两个特定目标来检验该假设：1）比较标准喂养方法与创新喂养策略包的临床结局，以及2）确定任一治疗成功或失败的病理生理机制。在目标-1下，我们将检验创新喂养策略包在实现经口喂养成功和降低婴儿GER-腹泻-修正症状评分方面更有效的假设。在目标2下，我们将通过利用我们的诊断工具来验证假设并验证初步数据的结果，以确定两个研究组之间在呼吸消化反射、食管清除机制、吞咽的肠道神经运动标志物和pH阻抗症状指数方面的差异。该方法是创新的，因为我们使用最先进的方法，包括多模式食管感觉激发方法，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。拟议的研究是重要的，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的依据，以完善GERD的治疗。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。 公共卫生相关性：拟议的研究与公共卫生有关，因为基于病理生理学的婴儿喂养方法将克服胃食管反流病婴儿呼吸消化系统疾病的负担。拟议的研究将克服进展的关键障碍，为脆弱婴儿的安全喂养模式的发展提供科学和经济的理由，并提高婴儿的消化健康，所有这些都与NIH（NIDDK）的使命有关。