A NEW APPROACH FOR THE TREATMENT OF ASTHMA

描述(由申请人提供)：这项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。虽然急性哮喘发作有多种不同的可能诱因，但所有此类发作的一个明显特征是气道壁的平滑肌过度收缩。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直接试图限制哮喘发作期间这种过度的平滑肌肉收缩。为此，目前拨款支持的现有工作已经证明了这种令人兴奋的新的创新方法治疗气道平滑肌的能力，永久性地限制了气道平滑肌缩短的能力。这一竞争性更新描述了新的目标，包括优化用于将射频能量输送到平滑肌的设备，这一过程被称为支气管热成形术。它还涉及新的建模和实验工作，使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·霍普金斯大学的生理实验室和专业知识与Asthmatx公司之间的密切合作伙伴关系，Asthmatx公司提供产品开发所涉及的机械和生物工程技能。这一提议的总体假设是，无论收缩的初始刺激是什么，用这一创新系统治疗呼吸道平滑肌将降低由平滑肌收缩引起的哮喘严重程度。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。在这项提案中，将有三个具体目标来解决这一假设。第一个目标将使用数学建模来确定射频(RF)治疗能量如何沿着呼吸道树在径向和轴向传播。第二个目标将使用从这个建模中获得的知识来测试将射频能量传递到呼吸道平滑肌的新设备。第三个目标将确定临床相关的生理变化对治疗效果的影响。因此，本BRP中提出的研究将允许优化一种设备，该设备具有有效治愈所有形式的人类哮喘的潜力，而不考虑病因。

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.