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).

嗜酸性食管炎（EOE）是对嗜酸性浸润的食物的普遍过敏反应 EOE可以导致食管重塑，疤痕，肌肉肥大和狭窄， 降低生活质量并增加食物撞击的风险。 EOE的诊断是通过找到上皮来进行的 内窥镜检查过程中获得的活检中的食管嗜酸性粒细胞。患者接受局部治疗 皮质类固醇或饮食排除，这两种都是需要重复内窥镜的慢性疗法 跟进。 依赖用于评估EOE患者的系列内窥镜活检的依赖，在此严重阻碍了进步 场地。据估计，EOE在美国的成本超过10亿美元，其中大部分是由于镇静/麻醉所致 内窥镜的要求。对于患者而言，内窥镜检查非常朴实，其中许多是 孩子们。另外，由于活检仅采样上皮，因此更深的组织的重塑不能是 对知识，诊断和治疗终点的差距进行了评估。由于这些原因，有一个专业 推动找到一个侵入性较低的诊断工具，该工具可以全面评估两种食管嗜酸性粒细胞 和EOE患者的上皮下重塑。 我们的实验室开发了一种称为束缚胶囊膜镜检查（TCE）的技术，涉及吞咽 在遍历10 µm分辨率的光学相干断层扫描（OCT）显微镜下进行的束缚药 胃肠道。该程序可以在未编辑的患者中进行，很快，并且非常偏爱 内窥镜检查。在这笔赠款中，我们将推进TCE，以便能够评估注射和 EOE患者的重塑。区分特征将包括大量分辨率提高到1- µm（µCT），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 极化灵敏度（PS），将提供有关胶原蛋白和肌肉含量深处的定量数据 食管。然后，PS-μoct将用于一项临床研究，以提高我们的理解 在基线和类固醇治疗后的食管注射和重塑（AIM 2）。我们还将进行 一项临床研究，可在饮食排除方案期间优化食物重新引入间隔（AIM 3）。