A NEW APPROACH FOR THE TREATMENT OF ASTHMA

描述（由申请人提供）：该提案将继续开发和优化一种创新的潜在哮喘临床治疗方法。尽管急性哮喘发作有多种不同的可能触发因素，但所有此类发作的一个定义特征是气道壁中平滑肌的过度收缩。尽管有这个共同的终点，但近年来大多数临床哮喘研究和治疗都集中在了解经常导致哮喘发作的免疫因素。相对较少的新研究直接集中在哮喘发作期间直接试图限制这种过度的平滑肌收缩。为此，现有的研究已经证明了这种令人兴奋的治疗气道平滑肌的新创新方法能够永久限制气道平滑肌缩短的能力。该竞争性更新描述了涉及优化用于向平滑肌输送射频能量的器械的新目标，该手术称为支气管热成形术。它还涉及新的建模和实验工作，采用最先进的定量成像来评估这些治疗在体内的有效性。该项目涉及约翰霍普金斯大学和Asthmatx公司的生理实验室和专业知识之间的密切合作伙伴关系，提供产品开发中涉及的机械和生物工程技术的公司。管理该提议的总体假设是，用该创新系统治疗气道平滑肌将降低由平滑肌收缩引起的哮喘严重程度，而不管收缩的起始刺激。这种方法最近在16名哮喘受试者的初步研究中得到了验证。在本提案中，三个具体目标将针对解决这一假设。第一个目标将使用数学建模来确定射频（RF）治疗能量如何沿气道树沿着径向和轴向传播。第二个目标将使用从该建模中获得的知识来测试向气道平滑肌输送射频能量的新器械。第三个目标是确定临床相关生理变化对治疗有效性的影响。因此，本BRP中提出的研究将允许优化具有有效治愈所有形式人类哮喘（无论病因如何）潜力的器械。

DESCRIPTION (provided by applicant): This proposal will continue the development and optimization of an innovative potential clinical treatment for asthma. Although there are a multitude of different possible triggers of an acute asthmatic attack, one defining feature of all such attacks is excessive contraction of the smooth muscle in the airway wall. Despite this common end point, most of the clinical asthma research and therapies in recent years have focused on understanding the immunologic factors that often lead to asthmatic attacks. Relatively little new research has focused directly on directly trying to limit this excessive smooth muscle contraction during an asthmatic attack. To this end, existing work supported by the current grant has already demonstrated the ability of this exciting new innovative method of treating the airway smooth muscle to permanently limit the ability of airway smooth muscle to shorten. This competitive renewal describes new objectives involving the optimization of the device that is used to deliver the RF energy to the smooth muscle, a procedure that is termed bronchial thermoplasty. It also involves new modeling and experimental work employing state of the art quantitative imaging to assess the effectiveness of these treatments in vivo. The project involves a close working partnership between the physiologic laboratories and expertise at the Johns Hopkins University and Asthmatx, Inc., the company that provides the mechanical and bioengineering skills involved in product development. The overall hypothesis governing this proposal is that, the treatment of airway smooth muscle with this innovative system will reduce asthma severity caused by smooth muscle contraction, regardless of the initiating stimulus for contraction. This approach has recently been validated in pilot study in 16 asthmatic subjects. In this proposal, three Specific Aims will be directed toward addressing this hypothesis. The first aim will use mathematical modeling to ascertain how the radiofrequency (RF) treatment energy spreads in radial and axial directions along the airway tree. The second aim will use the knowledge gained from this modeling to test new devices to deliver RF energy to the airway smooth muscle. The third aim will determine the impact of clinically relevant physiologic changes on treatment effectiveness. The studies proposed in this BRP will thus allow optimization of a device that has the potential to effectively cure all forms of human asthma regardless of the etiology.