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

光学相干断层扫描检测支气管热成形术后气道壁微结构的变化

• 批准号: 9609626
• 负责人: Jeffrey Thiboutot
• 金额: $ 5.74万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-30 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9609626
• 关键词: Accident and Emergency department; Acute; Address; Adopted; Airway Disease; Allergens; Asthma; Atrophic; Biological Markers; Blood Vessels; Bronchoconstriction; Caliber; Canis familiaris; Cartilage; Chronic; Cicatrix; Complex; Consensus; Data; Denervation; Disease; Distal; Edema; Epithelium; Evaluation; Excision; FDA approved; Funding; Future; General Population; Gland; Goals; Histologic; Hospitalization; Hour; Human; Hyperplasia; Hypertrophy; Image; Imagery; Inflammation; Inflammatory Response; Ionizing radiation; Left; Leucocytic infiltrate; Lung; Lung diseases; Measurement; Measures; Medical; Mentors; Methods; Microscopic; Modeling; Morphology; Obstruction; Office Visits; Optical Coherence Tomography; Optics; Pathologic; Patient Selection; Patients; Physiological; Positioning Attribute; Prediction of Response to Therapy; Procedures; Quality of life; Research Personnel; Resolution; Secondary to; Selection Criteria; Specimen; Technology; Thick; Time; Tissue imaging; Tissues; Translating; Translations; United States; Work; airway hyperresponsiveness; airway inflammation; airway remodeling; asthmatic; cost; experience; human subject; imaging modality; imaging system; improved; in vivo; individualized medicine; methacholine; minimally invasive; muscle form; muscle hypertrophy; new technology; optimal treatments; pre-clinical; predicting response; predictive marker; radiofrequency; respiratory smooth muscle; routine practice; skills; targeted treatment; treatment response

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.

项目摘要 在美国，估计有2500万人患有哮喘，尽管有最佳治疗，但 由于慢性气道炎症，超过10％的疾病。 气道重塑，哮喘会导致气流观测导致衰弱的流动 管理中的主要阶段专注于避免过敏原，同时减少炎症和 但是，支气管收缩；几乎没有疗法是病理学病理学病理学气道重塑。 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）是经批准的涡旋治疗严重哮喘的治疗 向气道的射频能量，目的是导致ASM销售减少 但是，响应性的人。 研究其功效，基本的作用机理以及缺乏选择标准以识别患者 谁最有可能对治疗做出反应。 直到最近，评估气道壁的微观结构（ASM，上皮，血管， 软骨，腺体）受到通过AN进行的病理评估的依赖 内窥镜方法，光学连贯性Tomagraphy（OCT）是一种最近开发的技术，能够 成像带有接近微观分辨率的体内气道壁的微观结构，这不是 目前可能 使用此技术的病理评估，OCT提供了一种最低侵入性的方法 我们对BT的理解。 我们将使用OCT进行非侵入性，以利用BT在气道上引起的纵向变化 壁式模型中的壁。 但是，在使用人类受试者之前，用于预测对BT的治疗反应的光学标志物 OCT的表征这些变化的能力必须得到验证。 急性和持续结构（目标1和2）和功能性（AIM 3）在BT中引起的气道变化 犬类模型。 用于人类受试者。