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

项目摘要 影响食管的慢性消化系统疾病，包括胃食管反流病 胃食管反流病（GERD）、嗜酸性食管炎（EoE）、贲门失弛缓症和功能性吞咽困难很常见， 沉重的经济负担。这些都是异质性条件，其病理生理发生在一个 根据异常酸暴露程度、运动功能障碍、丸剂保留和 食管超敏反应程度。症状与生理相关性较差，表明 其他过程影响症状体验。几乎一半的患者继续出现症状 尽管有一线治疗，但这些患者的治疗选择不足。有必要 更个性化的干预措施针对下意识操作以抑制的推注传输系统 食团传输和肌肉收缩的感觉。中枢介导的心理过程 例如食管过度警觉、灾难化和内脏超敏反应驱动症状 经验，独立于酸暴露，运动功能，或嗜酸性粒细胞组织学。自主神经 神经系统（ANS）唤醒，即对恐惧和过度警觉的生理“战或逃”反应， 这些心理过程。心率变异性（HRV），或心脏之间的时间间隔的变化 心跳，作为一个生物标志物的整体ANS功能。心率变异性越高， 以适应紧张的情况下，如当经历食道症状。研究较少，但 一个重要的结构是认知灵活性，或适当地改变思想和适应的能力 行为认知灵活性是一个可修改的结构，如果通过训练得到改善， 结果，并为行为治疗做好准备，否则这些患者可能是不良反应者。我们的目标是 根据机械和生物力学， 生理表型来自我们的生物生理建模CORE。然后，我们的目标是评估心脏 心率变异性生物反馈（HRVB），这是一种针对这四组患者的新型干预措施。患者将 按认知灵活性水平分层，那些被确定为低的人正在接受认知补救 治疗（CRT），一种使用认知练习来改善思维策略的简短干预。我们假设 当症状正在经历时，将HRVB应用于实时目标ANS唤醒，将有效地 增加HRV，减少症状，改善生活质量。我们还预计HRVB将减少 与对照组相比，食管过度警觉。我们假设CRT是一种可行的， 食管患者可接受的干预，并将与积极的变化， 认知灵活性，症状减轻，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 认知灵活性来定义管理和结果。研究结果将对 慢性食管疾病患者当前和未来的行为干预。

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.