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

项目总结 在美国，估计有2500万人患有哮喘，尽管有最佳的治疗方法， 超过10%的人患有严重疾病。由于慢性呼吸道炎症，支气管收缩，以及 呼吸道重塑，哮喘引起气流阻塞，导致虚弱加重。海流 管理的主要重点是避免过敏原，同时减少炎症和 支气管收缩；然而，很少有治疗方法可以专门针对病理性的气道重塑。 重症哮喘的一个显著特征是气道平滑肌(ASM)的增生和肥大。 支气管热成形术(BT)是一种被批准的治疗重症哮喘的内窥镜治疗方法， 射频能量进入呼吸道，目标是导致ASM破坏，从而减少 高反应性。然而，由于研究有限，BT还没有被应用到日常实践中 调查其疗效、潜在的作用机制，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)由于其对病理评估组织采集的依赖而受到限制。通过 光学相干层析成像(OCT)是最近发展起来的一种内窥镜方法，它能够 以近显微分辨率在体内成像气道壁的微观结构，这不是 以前是有可能的。这项新技术提供了消除对组织采集的需求的可能性 病理评估。使用这项技术，OCT提供了一种微创方法来解决 我们对英国电信的理解。 我们将使用OCT无创性地研究Bt对呼吸道的纵向变化 犬类模型中的墙。OCT对ASM的活体可视化提供了将ASM厚度作为 预测Bt治疗反应的光学生物标志物。然而，在用于人类受试者之前， OCT描述这些变化的能力必须得到验证。因此，本研究将使用OCT来确定 Bt致小鼠气道壁结构和功能的急性和持续性改变(目标1和目标2) 一只狗的模型。这项研究产生的临床前数据将是这项技术转化的关键 用于人类受试者。

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.