Regional Gas Trapping in Bronchoconstricted Asthmatics

描述（由申请人提供）：哮喘是一种发病率迅速增加的疾病，仅在美国就已经影响了超过1700万人。了解哮喘发作期间发生的潜在机械和生理变化的机制是非常重要的。该项目的长期目标是扩大对这些机制的理解，为开发诊断、监测和管理哮喘的改进方法提供基础。支气管收缩是哮喘的主要特征，其在肺内的空间分布对诊断和治疗具有广泛的意义。越来越多的实验工作表明，肺的异质性反应不能通过单个气道的独立行为的总和来预测。该建议的中心假设是，这种反应是肺的综合反应的反映，包括气道和实质之间的一系列平行相互作用。本研究主要关注该假说的三个关键方面：1)哮喘通气的平行异质性与气道树综合反应之间的联系；2)深度吸入（Dl’s）在气道阻塞的发展和恢复中的区域作用；3)通过深度吸入（Dl’s）重新打开肺部通气缺陷区域以改善吸入气溶胶药物沉积的连续和平行均匀性和有效性。这些研究将在健康人和哮喘患者中进行，并结合使用正电子发射成像和高分辨率CT获得的肺功能、结构和吸入气溶胶沉积的无创地形评估，以及肺力学的全局测量和建模。我们期望这些详细的解剖和功能数据将为该疾病的病理生理学提供新的见解，这将直接适用于患者护理，并将有助于推进气溶胶治疗领域。

DESCRIPTION (provided by applicant): Asthma is a disease of rapidly increasing incidence that already affects more than 17 million people in the United States alone. It is of major importance to understand the mechanisms responsible for underlying mechanical and physiological changes that occur during asthma exacerbations. The long-term objective of this project is to expand the understanding of these mechanisms to provide the foundations upon which to develop improved methods for diagnosing, monitoring and managing asthma. Bronchoconstriction is a cardinal feature of asthma, and its spatial distribution within the lungs has wide implications for diagnosis and therapy. An increasing amount of experimental work suggests that the heterogeneous response of the lung cannot be predicted by the summed independent behavior of individual airways. The central hypothesis to this proposal is that such response is a reflection of the integrated response of the lung including serial and parallel interactions amongst airways and parenchyma. This proposal focuses on three key aspects of this hypothesis: 1) the link between parallel heterogeneity in ventilation in asthma with the integrated response of the airway tree, 2) the regional effect of deep inhalations (Dl's) in the development of and recovery from airway obstruction, and 3) the reopening of ventilation defective regions of the lung with Dl's to improve the serial and parallel uniformity of inhaled aerosol drug deposition and effectiveness. The studies will be conducted in healthy persons and patients with asthma and combine non-invasive topographic assessments of lung function, structure and inhaled aerosol deposition, obtained with positron emission imaging and high resolution CT, with global measurements and modeling of lung mechanics. We expect that this detailed anatomical and functional data will provide new insights into the pathophysiology of the disease that will be directly applicable to patient care and will help advance the field of aerosol therapy.