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）是一种常见的食物过敏反应，引起嗜酸性粒细胞浸润 在食道里EoE可导致食管重塑、瘢痕形成、肌肉肥大和狭窄， 生活质量下降，食物嵌塞风险增加。EoE的诊断是通过发现上皮细胞 胃镜活检中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，这两种治疗都是需要反复内镜检查的慢性治疗 跟进 依赖于连续内镜活检来评估EoE患者显著阻碍了这方面的进展。 领域据估计，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 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，其中许多患者 孩子此外，由于活检仅对上皮进行取样，因此不能对更深的组织进行重塑。 评估，留下知识，诊断和治疗终点的差距。由于这些原因， 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 和上皮下重塑。 我们的实验室开发了一种称为栓系胶囊显微内镜（TCE）的技术， 系留式药丸，在穿越时进行10微米分辨率的光学相干断层扫描（OCT）显微镜检查， 胃肠道。该程序可以在未使用镇静剂的患者中完成，速度快，并且压倒性地优于 内镜在这项资助中，我们将推进TCE，使其能够评估炎症和 EoE患者的重塑。突出的特点将包括分辨率显著提高到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 偏振灵敏度（PS），将提供定量数据的胶原蛋白和肌肉含量深内 食道PS-µOCT随后将用于临床研究，以提高我们对 基线和类固醇治疗后的食管炎症和重塑（目的2）。我们还将进行 一项临床研究，以优化饮食排除协议期间的食物重新引入间隔（目标3）。