Transnasal Probe for Diagnosing Eosinophilic Esophagitis

描述（由申请方提供）：嗜酸性食管炎（EoE）是一种食管炎性疾病，被认为是由食物过敏引起的，其特征是食管粘膜内存在嗜酸性粒细胞。尽管它是一种相对较新的疾病，但EoE现在被认为在成人和儿童人群中很常见，并且发病率迅速上升。EoE患者可能会出现各种上消化道症状，从吞咽困难到食物嵌塞。专家担心，如果不及时治疗，EoE可能导致食管纤维化和狭窄形成。因此，目前建议治疗这种疾病，直到症状和嗜酸性粒细胞浸润已经解决。EoE治疗方案包括皮质类固醇和积极的饮食限制，然后逐渐重新进食。虽然这两种治疗方法都有效，但EoE在停止皮质类固醇后会恢复，需要多次尝试重新进食，以达到提供良好生活质量的饮食。因此，EoE患者的管理包括频繁随访，以监测患者对类固醇剂量和/或饮食变化的临床和组织病理学反应。这种策略对患者及其家属来说是艰巨的，并且昂贵，因为必须随着时间的推移进行多次内窥镜检查以获得食管活检并监测嗜酸性粒细胞计数。我们已经开发出一种新的技术，称为光谱编码共聚焦显微镜（SECM），这是能够被纳入到一个小直径的探针，并可以快速获得深度分辨的显微图像数据在大的上皮区域在体内。最初是为了评估食管的异型增生和癌症而开发的，我们最近发现这种成像方式也可以看到食管嗜酸性粒细胞的高度对比。内窥镜检查的大部分不便和近一半的成本是执行内窥镜检查程序所需的患者镇静的结果。在本提案中，我们将推进SECM技术，使其可用于监测食道嗜酸性粒细胞，而无需镇静、内窥镜检查或切除活检。我们将通过开发小型、灵活的经鼻SECM探头来完成这项任务，该探头可以在门诊环境中常规插入食管。结合新的高速SECM系统，该设备将自动成像食管的大部分和计数嗜酸性粒细胞。一旦器械构建完成，将进行确认研究，以证明该器械的准确性与内窥镜活检的准确性相当。这项研究的最终产品将是一种食管嗜酸性粒细胞监测工具，它比目前的标准治疗更便宜，耐受性更好。除了其直接的临床影响外，这项技术还可以用于未来的调查研究，以扩大我们对EoE和其他疾病（如以组织嗜酸性粒细胞增多为特征的哮喘）的了解。

DESCRIPTION (provided by applicant): Eosinophilic esophagitis (EoE) is an inflammatory condition of the esophagus, thought to be caused by food allergy, and characterized by the presence of eosinophils within the esophageal mucosa. Even though it is a relatively new disease, EoE is now recognized to be common in both adult and pediatric populations and rapidly rising in incidence. Patients with EoE can experience a variety of upper GI symptoms, ranging from dysphagia to food impaction. Experts fear that if left untreated, EoE may lead to esophageal fibrosis and stricture formation. It is therefore currently recommended that this disease be treated until the symptoms and the eosinophilic infiltrate have resolved. EoE therapy options include corticosteroids and aggressive dietary restriction followed by gradual food reintroduction. While both treatments are effective, EoE returns following cessation of corticosteroids and numerous attempts at food reintroduction are needed to arrive at a diet that provides a good quality of life. As a result, management of EoE patients involves frequent follow up to monitor the patient's clinical and histopathologic response to changes in steroid dosing and/or diet. This strategy is arduous for patients and their families, and costly, as multiple endoscopy sessions must be conducted over time to procure esophageal biopsies and monitor eosinophil counts. We have developed a new technology called spectrally-encoded confocal microscopy (SECM), that is capable of being incorporated into a small-diameter probe and can rapidly obtain depth-resolved microscopic image data over large epithelial areas in vivo. Originally developed to evaluate dysplasia and cancer of the esophagus, we have recently discovered that this imaging modality can also see esophageal eosinophils with a high degree of contrast. Much of the inconvenience and nearly half of the cost of endoscopy is a consequence of patient sedation that is required to perform the endoscopic procedure. In this proposal we will advance the SECM technology so that it can be used to monitor esophageal eosinophils without requiring sedation, endoscopy, or excisional biopsy. We will accomplish this task by developing small, flexible transnasal SECM probe that can be routinely inserted into the esophagus in the outpatient setting. In conjunction with a new high-speed SECM system, this device will automatically image a large portion of the esophagus and count eosinophils. Once the device has been constructed, validation studies will be conducted to demonstrate that the accuracy of this device is comparable to that of endoscopic biopsy. The end product of this research will be an esophageal eosinophil monitoring tool that is less expensive and far better tolerated than the current standard of care. Beyond its immediate clinical impact, this technology can also be used in future investigational studies to expand our knowledge of EoE and other diseases such as asthma that are characterized by tissue eosinophilia.