Changes in Airway Wall Microstructures Following Bronchial Thermoplasty Detected by Optical Coherence Tomography

项目摘要 在美国，估计有2500万人患有哮喘，尽管有最佳治疗， 超过10%的人留下了严重的疾病。由于慢性气道炎症，支气管收缩， 气道重塑，哮喘引起气流阻塞，导致衰弱性恶化。当前 管理的主要重点是避免过敏原，同时减少炎症， 支气管收缩;然而，很少有疗法可用于特异性靶向病理性气道重塑。 严重哮喘的标志性特征之一是气道平滑肌（ASM）增生和肥大。 支气管热成形术（BT）是一种经批准的治疗严重哮喘的内镜治疗方法， 将射频能量输送到气道，目的是破坏ASM， 高反应性然而，由于研究有限，BT尚未被纳入常规实践 研究其疗效、潜在作用机制以及缺乏识别患者的选择标准 最有可能对治疗有反应的人 直到最近，对气道壁（ASM、上皮、血管， 软骨、腺体）的局限性在于其依赖于用于病理评估的组织获取。通过一个 在内窥镜方法中，光学相干断层扫描（OCT）是最近开发的技术， 以接近显微镜的分辨率对体内气道壁的微观结构进行成像， 以前可能的。这种新技术提供了否定组织采集的需要的潜力， 病理学评价使用这种技术，OCT提供了一种微创方法来解决 我们对BT的理解 我们将使用OCT来非侵入性地研究BT在气道上引起的纵向变化 狗模型中的墙。使用OCT对ASM进行体内可视化提供了使用ASM厚度作为 用于预测对BT的治疗反应的光学生物标志物。然而，在用于人类受试者之前， 必须确认OCT表征这些变化的能力。因此，本研究将使用OCT来确定 急性和持续的结构（目标1和2）和功能（目标3）的变化，在气道壁由BT诱导， 一个犬类模型这项研究产生的临床前数据将是这项技术转化的关键 用于人体实验。

PROJECT SUMMARY In the United States, an estimated 25 million people suffer from asthma, and despite optimal treatment, upward of 10% are left with severe disease. Due to chronic airway inflammation, bronchoconstriction, and airway remodeling, asthma causes airflow obstruction leading to debilitating exacerbations. The current mainstay of management is focused on allergen avoidance, while reducing inflammation and bronchoconstriction; however, few therapies are available to specifically target pathologic airway remodeling. One of the hallmark features of severe asthma is airway smooth muscle (ASM) hyperplasia and hypertrophy. Bronchial Thermoplasty (BT) is an approved endoscopic treatment for severe asthma that delivers radiofrequency energy to the airways with the goal of causing ASM destruction leading to decreased hyperresponsiveness. However, BT has not yet been adopted into routine practice due to limited studies investigating its efficacy, underlying mechanism of action, and absence of selection criteria to identify patients who are most likely to respond to treatment. Until recently, evaluation of the microstructures of the airway wall (ASM, epithelium, blood vessels, cartilage, glands) was limited by its reliance on tissue acquisition for pathologic assessment. Performed via an endoscopic approach, optical coherence tomography (OCT) is a recently developed technology capable of imaging the microstructures of the airway wall in vivo with near microscopic resolution, which was not previously possible. This novel technology offers the potential to negate the need for tissue acquisition for pathologic evaluation. Using this technology, OCT offers a minimally invasive method to address the gaps in our understanding of BT. We will use OCT to non-invasively investigate the longitudinal changes induced by BT on the airway wall in a canine model. In vivo visualization of ASM with OCT offers the potential to use ASM thickness as an optical biomarker for the prediction of treatment response to BT. However, prior to use on human subjects, OCT’s ability to characterize these changes must be validated. Thus, this study will use OCT to determine the acute and persistent structural (Aims 1&2) and functional (Aim 3) changes in the airway wall induced by BT in a canine model. The preclinical data generated from this study will be key in the translation of this technology to use in human subjects.