Airway inflammation and airway remodeling

描述（由申请人提供）：气道重塑是指在哮喘气道中观察到的结构变化。尽管目前的NIH指南建议维持哮喘患者正常肺功能的目标，但目前的治疗策略并不专门针对气道重塑，因为导致重塑的细胞和分子机制尚未明确，因此治疗靶点也未得到很好的理解。因此，有一个重要的需要，以确定气道重塑介导的机制，使潜在的新疗法可以针对这些途径。此外，这些途径的表征可能导致非侵入性血液或痰生物标志物的发展，以识别，监测，也许子集， 患有哮喘和气道重塑的患者。该UCSD AADCRC提案将由大卫布罗德（医学教授）指导，包括三个项目（Broide，Croft，Escheraw），将调查暴露于过敏原和鼻病毒哮喘常见触发因素的哮喘患者的气道重塑机制。因此，将在所有三个项目中探索的总体假设是，暴露于过敏原触发过敏性哮喘患者的炎症和重塑途径的表达，这些过敏性哮喘患者因暴露于呼吸道病毒如鼻病毒而加剧。将在每个项目中探索并由哮喘患者样本驱动的特定假设是，先天免疫应答（气道上皮细胞、巨噬细胞、天然辅助细胞）在过敏性哮喘患者对环境触发物的炎症和气道重塑应答的启动和持续中发挥重要作用。这三个相互关联的项目将集中在“先天性炎症和气道重塑”（Broide，项目1），“TNF-R家族成员，炎症和重塑”（Croft，项目2）和“上皮GILZ炎症和重塑”（Escheraw，项目3），并得到管理核心A和“哮喘临床核心B”的支持，后者将是痰液、BAL、支气管内活检的来源，以及由核心B研究者提供的哮喘和对照受试者的血样（Ramsdell、Harrell和Thistlethwaite，UCSD; Proud和Leigh，卡尔加里大学; Hamid，麦吉尔大学）。根据RFA的要求，还提出了一个IOFM核心。

DESCRIPTION (provided by applicant): Airway remodeling is the term applied to the structural changes observed in the airway in asthma. Although current NIH guidelines recommend maintaining a goal of normal lung function in asthma, current therapeutic strategies do not specifically target airway remodeling as the cellular and molecular mechanisms that result in remodeling are not well defined and thus therapeutic targets are not well understood. Thus, there is an important need to identify mechanisms by which airway remodeling is mediated so that potential novel therapies could be directed at these pathways. In addition, characterization of these pathways could lead to the development of non-invasive blood or sputum biomarkers to identify, monitor, and perhaps subset, patients with asthma and remodeled airways. This UCSD AADCRC proposal will be directed by David Broide (Professor of Medicine) and include three projects (Broide, Croft, Zuraw) that will investigate mechanisms of airway remodeling in asthmatics exposed to allergen and rhinovirus common triggers of asthma. Thus, the overall hypothesis that will be explored in all three projects is that exposure to allergen triggers expression of inflammatory and remodeling pathways in allergic asthmatics that are exacerbated by exposure to respiratory viruses such as rhinovirus. The specific hypothesis that will be explored in each project and that will be driven by samples from asthmatics, is that the innate immune response (airway epithelium, macrophages, natural helper cells) play an important role in initiating and perpetuating the inflammatory and airway remodeling response to environmental triggers in allergic asthmatics. The three interrelated projects will focus on "Innate inflammation and airway remodeling" (Broide, Project 1), "TNF-R family members, inflammation and remodeling" (Croft, Project 2), and "Epithelial GILZ inflammation and remodeling" (Zuraw, Project 3) and be supported by Administrative Core A, and "Asthma Clinical Core B" which will be a source of sputum, BAL, endobronchial biopsy, and blood samples from asthma and control subjects provided by investigators in Core B (Ramsdell, Harrell, and Thistlethwaite, UCSD; Proud and Leigh, University of Calgary; and Hamid, McGill University). An lOFM Core is also proposed as requested by the RFA.