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

嗜酸性食管炎(EoE)是一种常见的对食物的过敏反应，可导致嗜酸性粒细胞渗入。 在食道里。EoE可导致食道重塑、瘢痕形成、肌肉肥大和狭窄， 生活质量下降，食物受到冲击的风险增加。EoE的诊断是通过发现上皮样病变 上内窥镜活检中的食道嗜酸性粒细胞增多症。患者接受外用药物治疗 皮质类固醇或饮食排斥，这两种都是需要重复内窥镜的慢性疗法 继续跟进。 依赖连续的内窥镜活检来评估EOE患者已经严重阻碍了这方面的进展 菲尔德。据估计，EoE在美国的价格超过10亿美元，其中很大一部分是由于镇静/麻醉 内窥镜检查的要求。内窥镜检查对患者来说是相当繁重的，其中许多人 孩子们。此外，由于活组织检查只对上皮细胞进行采样，深层组织的重塑不可能 评估，在知识、诊断和治疗终点方面留下空白。出于这些原因，有一个主要的 推动寻找一种侵入性较小的诊断工具，全面评估两种食道嗜酸性粒细胞 EoE患者的内皮下重塑。 我们的实验室已经开发出一种名为栓系胶囊内窥镜(TCE)的技术，它涉及到吞咽 10微米分辨率光学相干断层扫描(OCT)显微镜 胃肠道。该程序可以在未服用镇静剂的患者中进行，速度快，而且压倒性地优先于 内窥镜检查。在这笔赠款中，我们将推进TCE，使其能够同时评估炎症和 EoE患者的重塑。突出的特点将包括分辨率显著提高到1- 微米(微OCT)，以便可以识别和计数单个嗜酸性粒细胞。另一项进步将是实施 偏振敏感性(PS)，将提供胶原蛋白和肌肉成分的定量数据 食管。PS-OCT随后将用于临床研究，这将提高我们对 在基线和类固醇治疗后食管炎症和重塑的变化(目标2)。我们还将进行 一项优化饮食排除方案期间食物重新引入间隔的临床研究(目标3)。

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).