Responses of Contracted Airways and Parenchyma to Stretch in Vivo

有人认为，与健康受试者的正常气道扩张相比，哮喘受试者对深度吸气的气道收缩反应反映了该疾病的内在病理生理学。虽然很明显，气道平滑肌的特性必然与这种功能差异有关，但气道周围实质的特性可能同样重要。这一事实表明哮喘的一个重要问题可能与气道平滑肌在其动态实质环境中的行为有关。本研究将评估实质-气道相互作用的机制，特别关注肺膨胀和深度吸气与收缩平滑的反应

It has been suggested that the airway contractile response of asthmatic subjects to a deep inspiration, compared to normal airway dilation seen in healthy subjects, reflects an intrinsic pathophysiology of this disease. Although it is clear that properties of airway smooth muscle must be involved in this functional difference, the properties of the parenchyma that surround the airways may be equally important. This fact suggests that a significant problem in asthma may be related to airway smooth muscle behavior in its dynamic parenchymal environment. This proposal will evaluate mechanisms that underlie this parenchymal-airway interaction, particularly focused on the response to lung inflation and deep inspiration with contracted smooth muscle. This project contains several unique approaches to provide new information on how the lung responds to distension in vivo. First we use a novel method of challenging individual airways that allows us to separate the effects of agonist stimulation on individual airways, the entire airway tree, or the lung parenchyma. Second, by simultaneously using CT imaging with lung impedance measurements, we will be able to completely characterize the airway and dynamic parenchymal viscous and elastic responses. Third, by using a novel challenge method to anesthetize local airway nerves, we can determine how these nerves interact to determine whether the airway will respond with a contraction or relaxation following a deep inspiration. Specific aims of this proposal are designed to test two primary hypotheses related to this airway-parenchymal interaction in vivo: 1) The resultant behavior of airways following lung inflation depends on a balance between opposing physical and chemical effects on the smooth muscle; 2) parenchymal contraction can limit the ability of airways to narrow with pharmacologic or inflation stresses.