SEVERE ASTHMA RESEARCH PROGRAM (SARPII) IMAGING CORE

描述（由申请人提供）： 该辅助RFA提案的总体目标是更好地了解使用多排CT（MDCT）胸部的成像方式是否可以提供哮喘气道重塑的无创测量。严重哮喘研究计划（SARPII）的中心假设是，严重哮喘是许多相互作用过程的结果，这些相互作用过程不仅导致气道炎症、损伤和修复机制改变，而且存在通常调节损伤模式导致气道重塑的选定抗炎过程的失调。在本提案中，我们将利用前瞻性入组并仔细表征的重度哮喘受试者和适当的对照组（轻度-中度哮喘，正常受试者）的独特资源。我们建议在SARPII中添加成像方案，其中包括成像核心（爱荷华州大学）、形态学核心（华盛顿大学/匹兹堡大学）和Biostats核心（华盛顿大学）。作为该提案的一部分，受试者将接受MDCT胸部检查，然后进行支气管镜检查，引导成像，以指导在哪里可以获得支气管内活检，以获得重塑气道的最佳采样。我们建议在一组特征良好的重度和轻度哮喘成人受试者（n=200）和正常受试者中验证该技术将提供一种有价值的、临床有用的、非侵入性的气道重塑测量方法。因此，为了更好地确定与轻度哮喘或正常和患病对照相比，胸部MDCT是否可用作重度哮喘气道重塑的无创、间接测量，我们提出以下目的：I.标准化并评估SARPII研究中一个充分表征的重度哮喘受试者队列与轻度哮喘受试者和正常对照受试者的常见成像方案的可靠性，包括使用MDCT进行数据采集和图像分析。二.研究轻度和重度哮喘受试者的气道厚度的放射学测量是否与病理和生理标志物相关，并与SARPII研究中的正常对照组进行比较。三.在轻度和重度哮喘受试者中研究使用MDCT成像前瞻性识别气道重塑部位，并通过支气管内组织活检引导靶向支气管镜评估，并与SARPII研究中的正常对照进行比较。气道重塑被认为是导致哮喘中发生的肺功能长期下降的原因。我们建议，评价一种新的成像技术，多排CT（MDCT）胸部，在一个良好的特征组的严重和轻度哮喘患者和正常人将提供一个有价值的，临床上有用的，非侵入性的气道重塑措施。这种气道重塑的测量可能有助于识别可能发展为严重疾病的哮喘患者，以及可能从早期靶向积极治疗中获益的患者。(End摘要）

DESCRIPTION (provided by applicant): The overall goal of this Ancillary RFA proposal is to better understand whether an imaging modality using multidetector-row CT (MDCT) chest can provide a noninvasive measure of airway remodeling in asthma. The Severe Asthma Research Program's (SARPII) central hypothesis is that severe asthma is a consequence, in part, of numerous interactive processes that lead not only to airway inflammation, injury, and altered repair mechanisms, but that there is dysregulation of selected anti-inflammatory processes that normally modulate the injury pattern leading to airway remodeling. In this proposal, we will utilize this unique resource of prospectively enrolled and carefully characterized subjects with severe asthma and appropriate comparison groups (mild- moderate asthma, normal subjects). We propose to add an Imaging protocol to SARPII that will include an Imaging Core (University of Iowa), Morphology Core (Washington University/University of Pittsburgh), and a Biostats Core (Washington University). As part of this proposal, subjects will undergo MDCT chest then bronchoscopy with guided imaging to direct where endobronchial biopsies can be obtained for the optimal sampling of a remodeled airway. We propose that validating this technology in a well- characterized cohort of adult subjects (n=200) with severe and mild asthma and normal subjects will provide a valuable, clinically useful, noninvasive measure of airway remodeling. Accordingly, in order to better define whether MDCT chest can be used as a noninvasive, indirect measure of airway remodeling in severe asthma in comparison to mild asthma or normal and diseased controls, we propose the following aims: I. Standardize and assess the reliability of a common imaging protocol including both data acquisition and image analysis using MDCT in a well-characterized cohort of subjects with severe asthma in comparison to subjects with mild asthma and normal controls from the SARPII study. II. Investigate whether radiographic measures of airway thickness correlate with pathologic and physiologic markers in subjects with mild and severe asthma and in comparison to normal controls from the SARPII study. III. Investigate the use of imaging with MDCT to prospectively identify sites of airway remodeling and guide targeted bronchoscopic assessment with endobronchial tissue biopsy in subjects with mild and severe asthma and in comparison to normal controls from the SARPII study. Airway remodeling is felt to contribute to the long term decline in lung function that occurs in asthma. We propose that evaluating a new imaging technique, multidetector-row CT (MDCT) chest, in a well-characterized group of subjects with severe and mild asthma and normal subjects will provide a valuable, clinically useful, noninvasive measure of airway remodeling. This measure of airway remodeling may help identify individuals with asthma who are likely to develop severe disease and who may benefit from early targeted, aggressive therapy. (End of Abstract)