Less invasive assessment of inflammation and subepithelial remodeling in eosinophilic esophagitis patients

嗜酸性粒细胞性食管炎患者炎症和上皮下重塑的微创评估

• 批准号: 9762923
• 负责人: Guillermo J Tearney
• 金额: $ 58.96万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762923
• 关键词: Adult; Aftercare; Age; Allergens; Anesthesia procedures; Biological Markers; Biopsy; Birefringence; Blood; Cells; Child; Chronic; Cicatrix; Clinical; Clinical Research; Collagen; Correlative Study; Data; Deglutition; Deglutition Disorders; Development; Devices; Diagnosis; Diagnostic; Diet; Diet Modification; Disease; Disease remission; Economics; Endoscopic Biopsy; Endoscopy; Engineering; Eosinophilia; Eosinophilic Esophagitis; Epithelial; Epithelium; Esophageal; Esophageal Stenosis; Esophagus; Evidence Based Medicine; Exclusion; Expert Opinion; Family suidae; Fibrosis; Food; Gastrointestinal tract structure; Gold; Grant; Healthcare Systems; High Prevalence; Human; Hypersensitivity; Hypertrophy; Image; Imaging Device; Incidence; Individual; Infiltration; Inflammation; Inflammatory; Ingestion; Knowledge; Laboratories; Lateral; Lead; Location; Measurement; Methods; Microscopic; Microscopy; Modeling; Morphology; Muscle; Nature; Nausea and Vomiting; Optical Coherence Tomography; Organ; Outcome; Patients; Perforation; Procedures; Protocols documentation; Quality of life; Reporting; Research; Resolution; Risk; Sampling; Sedation procedure; Smooth Muscle; Steroids; Surface; Symptoms; Techniques; Technology; Testing; Therapeutic; Time; Tissue imaging; Tissues; Topical Corticosteroids; Treatment Efficacy; Validation; allergic response; base; capsule; cost; eosinophil; experience; follow-up; imaging modality; improved; in vivo; innovation; longitudinal analysis; microendoscopy; microscopic imaging; minimally invasive; muscle hypertrophy; new technology; pill; prototype; response; spatial relationship; therapy outcome; tool

Eosinophilic esophagitis (EoE) is a prevalent allergic response to food that causes eosinophilic infiltration in the esophagus. EoE can lead to esophageal remodeling, scarring, muscle hypertrophy, and stricture, decreasing quality of life and increasing risk of food impaction. Diagnosis of EoE is made by finding epithelial esophageal eosinophilia in biopsies acquired during upper endoscopy. Patients are treated with topical corticosteroids or dietary exclusion, both of which are chronic therapies that require repeated endoscopic follow up. Reliance on serial endoscopic biopsy for evaluating EoE patients has significantly hindered progress in this field. It is estimated that EoE costs over 1 billion dollars in the US, much of which is due to sedation/anesthesia requirements of endoscopy. Endoscopic exams are quite burdensome for patients, many of whom are children. Also, because biopsies only sample the epithelium, remodeling of deeper tissue cannot be evaluated, leaving gaps in knowledge, diagnosis, and treatment endpoints. For these reasons, there is a major push to find a less invasive diagnostic tool that comprehensively evaluates both esophageal eosinophils and subepithelial remodeling in EoE patients. Our lab has developed a technique called tethered capsule endomicroscopy (TCE) that involves swallowing a tethered pill that conducts 10-µm-resolution optical coherence tomography (OCT) microscopy as it traverses the GI tract. The procedure can be done in unsedated patients, is rapid, and is overwhelmingly preferred over endoscopy. In this grant, we will advance TCE so that it is capable of assessing both inflammation and remodeling in EoE patients. Distinguishing features will include a significant increase in resolution to 1- µm (µOCT) so that individual eosinophils can be identified and counted. Another advance will be implementation of polarization sensitivity (PS) that will provide quantitative data on collagen and muscle content deep within the esophagus. PS-µOCT will then be used in a clinical study that will improve our understanding of esophageal inflammation and remodeling at baseline and after steroid treatment (Aim 2). We will also conduct a clinical study to optimize food re-introduction intervals during dietary exclusion protocols (Aim 3).

嗜酸性粒细胞性食管炎 (EoE) 是一种常见的食物过敏反应，可导致嗜酸性粒细胞浸润 在食道中。 EoE 可导致食管重塑、疤痕、肌肉肥大和狭窄， 生活质量下降，食物嵌塞的风险增加。 EoE 的诊断是通过发现上皮细胞来进行的 上消化道内窥镜检查期间获得的活检标本中存在食管嗜酸性粒细胞增多。患者接受局部治疗 皮质类固醇或饮食排除，这两者都是需要反复内镜检查的慢性疗法 跟进。 依赖连续内窥镜活检来评估 EoE 患者严重阻碍了这方面的进展 场地。据估计，EoE 在美国花费超过 10 亿美元，其中大部分是由于镇静/麻醉 内窥镜检查的要求。内窥镜检查对于患者来说是相当繁重的，其中许多人 孩子们。此外，由于活检仅对上皮进行取样，因此无法进行更深层次组织的重塑。 评估，在知识、诊断和治疗终点方面留下差距。由于这些原因，有一个主要的 推动寻找一种侵入性较小的诊断工具，全面评估食管嗜酸性粒细胞 和 EoE 患者的上皮下重塑。 我们的实验室开发了一种称为系留胶囊内窥镜检查 (TCE) 的技术，该技术涉及吞咽 系留药丸在穿过物体时可进行 10 µm 分辨率的光学相干断层扫描 (OCT) 显微镜检查 胃肠道。该手术可以在未镇静的患者中进行，速度快，并且绝对优于 内窥镜检查。在这笔赠款中，我们将推进 TCE，使其能够评估炎症和 EoE 患者的重塑。显着特征包括分辨率显着提高至 1- µm (µOCT)，以便可以识别和计数单个嗜酸性粒细胞。另一个进步将是实施 偏振敏感度 (PS)，将提供深层胶原蛋白和肌肉含量的定量数据 食管。 PS-μOCT 随后将用于临床研究，以提高我们的理解 基线时和类固醇治疗后的食管炎症和重塑（目标 2）。我们还将进行 一项旨在优化饮食排除方案期间重新引入食物间隔的临床研究（目标 3）。