Redistribution of pulmonary perfusion during bronchoconstriction in asthma

描述（由申请人提供）：哮喘在美国影响超过1700万人，并且发病率正在上升。哮喘的研究主要集中在气道上，然而，对哮喘发作时局部肺灌注如何变化知之甚少。我们实验室最近使用正电子发射断层扫描（PET）功能成像的研究首次表明，在甲基苯丙胺引起的支气管收缩期间，自发呼吸的哮喘患者会发生剧烈的灌注再分布，远离低通气的斑块区域。本研究的长期目标是了解哮喘支气管收缩时局部灌注再分配的机制和改变因素。在这个项目中要测试的主要假设是：1)从通气缺陷处重新分配灌注主要是由缺氧肺血管收缩引起的，而不仅仅是甲基苯丙胺引起的支气管收缩的产物；2)对于给定程度的收缩刺激，与俯卧位相比，仰卧位时将血流从通风不良的部位重新分配的效果较差，因为重力会阻碍缺氧血管收缩的效果。这些假设将通过最先进的PET-CT区域灌注和通气功能成像进行验证，具体目的如下：1)评估在甲丙胺诱导的支气管收缩期间，通过呼吸高浓度氧消除缺氧刺激是否会减弱灌注的再分配（SA-1A）。2)评估在其他支气管收缩刺激引起的支气管收缩期间是否发生类似的灌注再分布，如果发生，评估缺氧肺血管收缩参与该再分布的程度（SA-1B）。3)比较俯卧位和仰卧位呼吸和不呼吸高氧浓度（SA-2）时远离通风不良区域的灌注再分布的大小。这项研究旨在提高我们对哮喘发作期间肺部血流和气流匹配机制的理解，以及哮喘发作后恢复期间这些机制的变化。了解这一重要的肺功能可能会改善哮喘治疗，并可能减少哮喘相关的死亡。每20个美国人中就有一个患有哮喘。在哮喘发作时，肺试图使气流和血液流动相匹配，以维持氧气输送到重要器官。导致哮喘死亡的原因之一可能是肺执行这一重要功能的能力受损。这项研究将研究哮喘发作时气流和血流的匹配机制，以便开发更好的治疗方法来预防哮喘死亡。

DESCRIPTION (provided by applicant): Asthma affects over 17 million people in the United States and the incidence is rising. Research in asthma has focused on the airways, however, little is known about how regional pulmonary perfusion changes during an asthma attack. Recent studies from our lab using positron emission tomography (PET) functional imaging have shown for the first time that dramatic perfusion redistribution, away from patchy areas of low ventilation, take place in spontaneously breathing human subjects with asthma during methacholine-induced bronchoconstriction. The long-term objective of this research is to understand the mechanisms of, and factors that modify, the regional perfusion redistribution during bronchoconstriction in asthma. The main hypotheses to be tested in this project are 1) The redistribution of perfusion away from ventilation defects is primarily caused by hypoxic pulmonary vasoconstriction and is not solely an artifact of methacholine-induced bronchoconstriction and 2) For a given degree of constrictive stimulus, the redistribution of perfusion away from poorly ventilated areas will be less effective in the supine than in the prone position because gravitational forces would tend to oppose the effectiveness of hypoxic vasoconstriction. These hypotheses will be tested using state-of-the-art PET-CT functional imaging of regional perfusion and ventilation with the following specific aims: 1) Assess whether elimination of the hypoxic stimulus by breathing a high oxygen concentration blunts the redistribution of perfusion during methacholine-induced bronchoconstriction (SA-1A). 2) Assess whether a similar perfusion redistribution occurs during bronchoconstriction induced by other bronchoconstrictive stimuli and, if so, evaluate the extent to which hypoxic pulmonary vasoconstriction is involved in that redistribution (SA-1B). 3) Compare the magnitude of redistribution of perfusion away from poorly ventilated regions in the prone and supine positions breathing with and without a high oxygen concentration (SA-2). This research is designed to improve our understanding of the mechanisms that match blood flow and airflow in the lungs during an asthma attack and how these change during recovery from an asthma attack. Knowledge of this important lung function may lead to improved asthma therapy and possibly reduce asthma-related deaths. Asthma affects one out of every twenty Americans. During an asthma attack, the lung tries to match airflow and blood flow in order to maintain oxygen delivery to vital organs. One of the causes of asthma deaths may be impairment in the ability of the lung to perform this important function. This research will study the mechanisms for matching airflow and blood flow during an asthma attack so that better treatments can be developed to prevent asthma deaths.