基于OCT技术的支气管热成形术治疗重症哮喘气道重塑的病理生理机制研究

Airway remodeling is a principal characteristic of asthma. Bronchial thermoplasty (BT), aiming at airway wall, is a novel non-drug treatment for patients with severe asthma. Nevertheless, some patients would not respond to BT treatment, owing to the poor knowledge of pathophysiologic mechanisms of BT. Optical coherence tomography (OCT), also called “optical biopsy”, is a novel non-invasive imaging technique which can detect the airway wall microstructure clearly. In our previous study, we have validated usefulness of OCT in assessing proximal and distal airway structures of human compared with histology (Respir Med 2015). Next, we successfully used OCT to detect the small airway structure in chronic obstructive pulmonary disease (CHEST 2016). In this study, first, we aim to explore the OCT imaging characteristics of airway structure in severe asthma through analysis of animal models and clinical cases. Secondly, combined with OCT imaging, immunohistochemical staining was performed to assess the change of airway smooth muscle, neurocyte and inflammatory cell by SMA, PGP9.5 and ECP before and after BT, for purpose of exploring the mechanisms of BT for airway remodeling. Thirdly, OCT-based evaluation of asthmatic small airway structure and possible nervous and inflammatory indirectly pathophysiological mechanisms of BT will be explored. The significance of this study lies in evidences based on OCT imaging and immunohistochemical staining will be provided for the strategy in treating severe asthma including BT selection for optimal severe asthma candidates.

气道重塑是重症哮喘的主要病理特征，支气管热成形术（BT）是热消融气道壁治疗重症哮喘的非药物新方法，但部分病例疗效欠佳，目前对BT治疗气道重塑的病理生理机制仍未完全明确。光学相干断层扫描(OCT) 是一种可清晰显示气道显微结构的无创新技术（被称为“光学活检”），前期我们已证实其与组织学结构相对应（RespirMed2015），并应用于COPD小气道结构探查（CHEST2016）。本研究拟1、通过哮喘犬模型和病例研究明确OCT成像对哮喘气道结构的评估作用；2、分析BT前后消融气道壁组织成分（SMA、PGP9.5、ECP免疫标记平滑肌、神经及炎症细胞）的变化与OCT成像改变的相关性，探索BT对哮喘气道重塑治疗机制；3、通过OCT和免疫组化分析未消融小气道肺组织结构改变，提出BT治疗可能的神经及炎症调节间接作用机制。研究将阐明BT治疗重症哮喘气道重塑的病理生理机制，有助BT疗效预测和有效人群筛选。

重症哮喘仅占哮喘人群6%，但其急诊就诊率、住院率确实轻中度患者的20倍，带来巨大的患者及社会负担，是严重的公共卫生问题。气道重塑是重症哮喘的主要病理特征，支气管热成形术（BT）是针对重症哮喘的非药物治疗新手段。BT疗效显著，但其作用机制尚未完全阐明，因此本项目基于前期在光学相干断层扫描（OCT）方面的研究基础，构建比格犬重症哮喘模型，通过动物实验证明BT除平滑肌消融的作用外，还存在神经消融、杯状细胞减少、减轻气道炎症的治疗作用。进一步我们探索了正常人与哮喘患者小气道结构改变，并以此为基础探索BT有效患者与BT无效患者之间的差异，建立了基于OCT的哮喘患者BT疗效预测模型。该项目的实施，进一步阐明了BT治疗重症哮喘气道重塑的病理生理机制，并实现了BT疗效预测及有效人群的筛选。