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

项目总结 影响食道的慢性消化系统疾病，包括胃食道反流病 (GERD)，嗜酸性食管炎(EoE)，失弛缓症和功能性吞咽困难是常见的，并构成 巨大的经济负担。这些都是异质性的疾病，其病理生理发生在 根据异常酸暴露程度、运动功能障碍、丸剂滞留和 食道过敏程度。症状与生理的相关性很差，这表明 其他过程会影响症状体验。几乎一半的患者继续出现症状。 尽管有一线治疗，但这些患者没有足够的治疗选择。有必要 更多针对团注运输系统的个性化干预措施，这些干预措施潜意识地运行以抑制 对推进剂传输和肌肉收缩的感知。中枢调节的心理过程 如食道过度警觉、灾难和内脏过敏驾驶症状 经验，与酸暴露、运动功能或嗜酸性粒细胞增多症组织学无关。自主神经 系统(ANS)唤醒，即对恐惧和高度警觉的生理“战斗或逃跑”反应，持续存在 这些心理过程。心率变异性(HRV)，或心脏之间时间间隔的变化 Beats，可作为ANS整体功能的生物标志物。心率变异性越高，说明能力越强 以适应有压力的情况，如遇到食道症状时。一个研究较少的人，但 重要的结构是认知灵活性，或适当地转移思想和适应的能力 行为。认知灵活性是一种可修改的结构，如果通过训练提高，就可以提高 结果，并使患者做好接受行为治疗的准备，否则他们可能反应不佳。我们的目标是 在明确定义的患者群体中，根据机械和 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)，一种针对这四个患者组的新干预措施。病人将会是 根据认知灵活性水平进行分层，那些被确定为低认知补救的人 治疗(CRT)，一种短暂的干预，使用认知练习来改善思维策略。我们假设 当症状正在体验时，应用HRVB实时对准ANS觉醒，将在 提高心率变异性，减轻症状，提高生活质量。我们还预计HRVB将会减少 与对照组相比，食道高度警觉。我们假设CRT将是一种可行的 对食道患者可接受的干预，并将与积极的变化相关 认知灵活性，减少症状，提高生活质量。最后，我们的目标是开发一个 利用食道扩张性生物标志物、心率变异性指标和指标的综合预测模型 定义管理和结果的认知灵活性。这一结果将对 针对慢性食道疾病患者的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.