PREDICTORS OF RESPONSE TO BRONCHIAL THERMOPLASTY IN SEVERE ASTHMA

 描述（由申请人提供）：本提案描述了一个为期五年的研究和培训计划，将促进Ajay Sheshadri博士向独立学术研究人员的过渡。Ajay在临床研究和医学方面有很强的背景，并完成了内科和肺/重症监护医学的研究生培训。该提案的主要目标是为Sheshadri博士提供必要的框架和支持，以实现其作为临床研究者的职业目标，过渡到使用先进成像技术进行阻塞性气道疾病的独立科学研究。 拟议的研究计划将侧重于以患者为基础的方法，以确定严重哮喘患者对支气管热成形术反应的临床和影像学预测因素。支气管热成形术是一种新型的基于器械的治疗方法，通过在重度哮喘患者中使用射频能量来减少气道平滑肌，从而降低急性发作率并改善生活质量。这项研究将招募三年以上的严重哮喘患者，并使用多种临床和新型成像方式详细描述他们的特征。然后，这些变量将用于确定支气管热成形术反应的预测因子，如皮质类固醇剂量减少或哮喘特异性生活质量改善所定义。 目的1：通过测量支气管热成形术前和后12个月的以下指标，确定支气管热成形术反应的临床预测因素：肺功能检查、乙酰甲胆碱支气管激发、痰液炎症、呼出一氧化氮、哮喘特异性生活质量、哮喘控制、口服和吸入类固醇剂量以及医疗保健利用。受试者的临床特征将有助于我们检验以下假设：基线生活质量较低的患者在支气管热成形术后更有可能减少口服或吸入类固醇剂量。目的2关注于使用新的气道壁厚度和肺密度定量测量来确定支气管热成形术后生活质量改善的预测因素。受试者的影像学特征将有助于我们检验以下假设：根据CT上空气滞留增加的测量结果，患有更多小气道疾病的患者不太可能对支气管热成形术有充分的反应。 我们在重度哮喘定量研究中使用的标准化成像采集和分析方面的丰富经验允许对文献中尚未描述的支气管热成形术反应的成像预测因子进行高保真度分析。总之，这些目标将允许对重度哮喘患者进行广泛的表征，目的是揭示应答者和非应答者表型，以预测对特定治疗的应答。拟议的应用将使Sheshadri博士能够发展高水平的研究事业，专注于开发新型定量成像技术，以增强阻塞性气道疾病的表型特征。

 DESCRIPTION (provided by applicant): This proposal describes a five-year research and training plan that will facilitate the transition of Dr. Ajay Sheshadri, MD to an independent academic researcher. Ajay has a strong background in clinical research and medicine and has completed post-graduate training in Internal Medicine and Pulmonary/Critical Care Medicine. The primary goal of this proposal is to provide the framework and support necessary for Dr. Sheshadri to fulfill his career goals as a clinical investigator through transition to independent scientific investigation in the use of advanced imaging in obstructive airway diseases. The proposed research plan will focus on a patient-based approach to identifying clinical and imaging predictors of response to bronchial thermoplasty in severe asthma. Bronchial thermoplasty is a novel device-based therapy that decreases airway smooth muscle through the use of radiofrequency energy in severe asthma, decreasing exacerbation rates and improving quality of life. The proposed study will enroll patients with severe asthma over three years and characterize them in detail using multiple clinical and novel imaging modalities. These variables will then be used to determine predictors of response to bronchial thermoplasty as defined by a reduction in corticosteroid dose or improvement in asthma- specific quality of life. Aim 1 focuses on identifying clinical predictors of response to bronchial thermoplasty by measuring the following before and 12 months after bronchial thermoplasty: pulmonary function tests, methacholine bronchoprovocation, sputum inflammation, exhaled nitric oxide, asthma-specific quality of life, asthma control, oral and inhaled steroid dose, and healthcare utilization. This clinical characterization of subjects will help us test the hypothesis that patients with lower baseline quality of life are more likely to have a reduction in oral or inhaled steroid dose after bronchial thermoplasty. Aim 2 focuses on the use of novel quantitative measures of airway wall thickness and lung densitometry to determine predictors of improvement in quality of life after bronchial thermoplasty. This imaging characterization of subjects will help us test the hypothesis that patients with more small airway disease, as measured by increased air trapping on CT, are less likely to have an adequate response to bronchial thermoplasty. Our extensive experience in standardizing imaging acquisition and analysis for use in quantitative studies of severe asthma allow for high-fidelity analyses of imaging predictors of response to bronchial thermoplasty that have not been described in the literature. Together, these aims will allow for an extensive characterization of patients with severe asthma with the goal of revealing responder and non-responder phenotypes to predict response to a specific therapy. The proposed application will allow Dr. Sheshadri to develop a high-level research career focused on developing novel quantitative imaging techniques to augment phenotypic characterization of obstructive airway diseases.