Interaction between bolus transport mechanics and psychologic factors in modulating esophageal symptoms

食团输送力学与心理因素在调节食管症状中的相互作用

• 批准号: 10200798
• 负责人: LAURIE A KEEFER
• 金额: $ 39.08万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200798
• 关键词: Achalasia; Acids; Affect; Anatomy; Arousal; Autonomic nervous system; Behavior; Behavior Therapy; Benign; Biofeedback; Biofeedback Training; Biological Markers; Biomechanics; Bolus Infusion; Brain; Chest Pain; Chronic; Cognitive; Cognitive remediation; Complex; Data; Deglutition Disorders; Diagnosis; Disease; Economic Burden; Eosinophilia; Eosinophilic Esophagitis; Esophageal Diseases; Esophagus; Esthesia; Exercise; Fright; Functional disorder; Future; Gastroesophageal reflux disease; Generations; Goals; Health system; Heart; Histology; Hypersensitivity; Impairment; Incidence; Individual; Intervention; Lead; Link; Malnutrition; Measures; Mechanics; Mediating; Modeling; Monitor; Morbidity - disease rate; Muscle Contraction; Nervous System Physiology; Operating System; Outcome; Patient Outcomes Assessments; Patients; Perception; Phenotype; Physiological; Physiology; Population; Predictive Value; Process; Psychological Factors; Quality of life; Reporting; Research; Role; Severities; Signal Transduction; Statistical Models; Stress; Subconscious; Symptoms; Thinking; Time; Tissues; Training; Variant; Visceral; attentional bias; base; brief intervention; cell motility; cognitive process; design; effectiveness testing; experience; experimental study; fighting; flexibility; functional outcomes; heart rate variability; improved; improved functioning; improved outcome; mathematical model; mechanical properties; mortality; motor disorder; neuromuscular; novel; patient population; personalized intervention; population based; predictive modeling; psychologic; psychosocial; reduce symptoms; response; symptomatic improvement; time interval; treatment response

PROJECT SUMMARY Chronic digestive illness affecting the esophagus, including gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), achalasia and functional dysphagia are common and pose a significant economic burden. These are heterogeneous conditions whose pathophysiology occurs on a wide spectrum based on degree of abnormal acid exposure, motor dysfunction, bolus retention and degree of esophageal hypersensitivity. Symptom-to-physiology correlations are poor, indicating that other processes influence symptom experience. Almost half of patients continue to experience symptoms despite first-line treatments, leaving these patients with inadequate treatment options. There is a need for more personalized interventions targeting the bolus transit system that operate subconsciously to suppress the perception of bolus transit and muscle contraction. Centrally-mediated psychological processes such as esophageal hypervigilance, catastrophizing, and visceral hypersensitivity drive symptom experience, independent of acid exposure, motility function, or eosinophilia histology. Autonomic nervous system (ANS) arousal, the physiological “fight-or-flight” response to fear and hypervigilance, perpetuates these psychological processes. Heart rate variability (HRV), or the variation in time intervals between heart beats, serves as a biomarker for overall ANS functioning. Higher HRV is indicative of a greater ability to adapt to stressful situations, such as when experiencing esophageal symptoms. A less studied, yet important construct is cognitive flexibility, or the ability to appropriately shift thoughts and adapt behavior. Cognitive flexibility is a modifiable construct that if improved through training, can improve outcomes and prepare patients for behavioral treatments who may otherwise be poor responders. We aim to characterize the degree of cognitive flexibility in well-defined patient populations based on mechanical and physiological phenotypes derived from our biophysiologic modeling CORE. Then, we aim to evaluate heart rate variability biofeedback (HRVB), a novel intervention for these four patient groups. Patients will be stratified by cognitive flexibility level, with those identified as low undergoing Cognitive Remediation Therapy (CRT), a brief intervention using cognitive exercises to improve thinking strategies. We hypothesize applying HRVB to target ANS arousal in real-time, as the symptoms are being experienced, will be effective in increasing HRV, decreasing symptoms, and improving quality of life. We also expect HRVB will decrease esophageal hypervigilance in comparison to controls. We hypothesize CRT will be a feasible and acceptable intervention for esophageal patients, and will be associated with positive changes in cognitive flexibility, decreased symptoms, and improved quality of life. Finally, we aim to develop an integrative predictive model using biomarkers of esophageal distensibility, measures of HRV and measures of cognitive flexibility to define management and outcomes. The results will have implications for current and future behavioral interventions for individuals with chronic esophageal disorders.

项目概要 影响食道的慢性消化系统疾病，包括胃食管反流病 （GERD）、嗜酸性粒细胞性食管炎（EoE）、贲门失弛缓症和功能性吞咽困难很常见，并引起 重大经济负担。这些是异质性疾病，其病理生理学发生在 基于异常酸暴露程度、运动功能障碍、推注滞留和 食管过敏的程度。症状与生理学的相关性很差，表明 其他过程影响症状体验。近一半的患者继续出现症状 尽管进行了一线治疗，这些患者仍然没有足够的治疗选择。有必要 针对丸剂转运系统进行更个性化的干预，该系统潜意识地运作以抑制 对推注转运和肌肉收缩的感知。中枢介导的心理过程 例如食管过度警觉、灾难化和内脏过敏驱动症状 经验，与酸暴露、运动功能或嗜酸性粒细胞增多组织学无关。自律神经 神经系统（ANS）唤醒，即对恐惧和过度警觉的生理“战斗或逃跑”反应，持续存在 这些心理过程。心率变异性 (HRV)，或心跳之间的时间间隔变化 节拍，作为整体 ANS 功能的生物标志物。 HRV 越高表明能力越强 适应压力情况，例如出现食道症状时。研究较少，但 重要的构建是认知灵活性，或者适当地转变思想和适应的能力 行为。认知灵活性是一种可修改的结构，如果通过培训加以改进，可以提高 并为患者做好行为治疗的准备，否则这些患者可能反应不佳。我们的目标是 基于机械和方法来表征明确定义的患者群体的认知灵活性程度 生理表型源自我们的生物生理学建模核心。然后，我们的目标是评估心脏 速率变异性生物反馈（HRVB）是针对这四个患者组的一种新颖干预措施。患者将会 按认知灵活性水平分层，那些被确定为低水平的人正在接受认知矫正 治疗 (CRT)，一种使用认知练习来改善思维策略的简短干预措施。我们假设 当症状出现时，应用 HRVB 实时定位 ANS 唤醒，将有效 增加 HRV、减少症状并提高生活质量。我们还预计 HRVB 将下降 与对照组相比，食管高度警惕。我们假设 CRT 将是一种可行且 食管患者可接受的干预措施，并将与食管患者的积极变化相关 认知灵活性、症状减轻和生活质量提高。最后，我们的目标是开发一个 使用食管扩张性生物标志物、HRV 测量和测量的综合预测模型 定义管理和结果的认知灵活性。结果将产生影响 针对慢性食管疾病患者当前和未来的行为干预。