PREDICTORS OF RESPONSE TO BRONCHIAL THERMOPLASTY IN SEVERE ASTHMA

严重哮喘支气管热成形术反应的预测因素

• 批准号: 9034407
• 负责人: Ajay Sheshadri
• 金额: $ 15.36万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9034407
• 关键词: Accounting; Address; Adrenal Cortex Hormones; Adverse effects; Affect; Air; Alternative Therapies; Asthma; Breathing; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Bronchoscopy; Characteristics; Chest; Clinical; Clinical Investigator; Clinical Medicine; Clinical Research; Clinical/Radiologic; Critical Care; Defect; Densitometry; Devices; Dose; Emergency department visit; Enrollment; Environmental air flow; Exhalation; Fibrosis; Gases; Goals; Health Expenditures; Helium; Hyperplasia; Hypertrophy; Image; Image Analysis; Imaging Techniques; Inflammation; Internal Medicine; Investigation; Literature; Lung; Magnetic Resonance Imaging; Measurement; Measures; Medicine; Methods; Morbidity - disease rate; Nitric Oxide; Obstructive Lung Diseases; Oral; Patient-Focused Outcomes; Patients; Peak Expiratory Flow; Phase; Phenotype; Population; Protocols documentation; Public Health; Pulmonary function tests; Quality of life; Randomized; Research; Research Personnel; Research Training; Resources; Respiratory physiology; Risk; Safety; Severities; Sputum; Steroids; Testing; Therapeutic; Thick; Training; United States; Work; X-Ray Computed Tomography; adverse outcome; airway inflammation; airway remodeling; asthmatic; asthmatic patient; base; career; clinical predictors; cohort; control trial; conventional therapy; cost; experience; health care service utilization; high risk; imaging modality; improved; insight; methacholine; morphometry; muscle form; novel; novel therapeutics; predicting response; prospective; public health relevance; pulmonary function; quantitative imaging; radiofrequency; respiratory smooth muscle; responders and non-responders; response; small airways disease; tool

 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.

 描述（由适用提供）：该提案描述了一项为期五年的研究和培训计划，该计划将支持马里兰州Ajay Sheshadri博士向独立学术研究员的过渡。阿杰（Ajay）在临床研究和医学方面具有强大的背景，并完成了内科和肺部/重症监护医学的研究生培训。该提案的主要目标是为Sheshadri博士提供所必需的框架和支持，以实现他作为临床研究者的职业目标，通过过渡到在阻塞气道疾病中使用高级成像的独立科学研究。拟议的研究计划将重点介绍一种基于患者的方法，用于识别严重哮喘中对支气管热成形术反应的临床和成像预测指标。支气管热成形术是一种基于设备的新型治疗，可通过在严重哮喘中使用射频能量来降低气道平滑肌，从而降低加重率并改善生活质量。拟议的研究将在三年内招募严重哮喘的患者，并使用多种临床和新型成像方式详细介绍他们。然后，这些变量将用于确定对支气管热成形术的反应预测因素，如皮质类固醇剂量的降低或哮喘特异性生活质量的改善所定义。 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 injection, exhausted nitric oxide, asthma-specific quality of life, asthma control, oral and inherited stereoid dose, and healthcare utilization.对受试者的临床表征将有助于我们检验以下假设：基线生活质量较低的患者更有可能减少支气管热成形术后口服或遗传的立体剂量。 AIM 2的重点是使用新型气道壁厚度和肺光密度法的定量测量，以确定支气管热成形术后生活质量改善的预测指标。对受试者的这种成像表征将有助于我们检验以下假设：通过增加CT空气捕获来衡量，具有更多小型气道疾病的患者在标准化成像获取和分析中具有适当的经验，用于用于对严重哮喘的定量研究，允许对对纤维化热的成像响应的高度分析的预测指标，而不是对纤维化热的成像预测的分析，而不是对纤维化热的成像预测的描述。总之，这些目标将允许对严重哮喘患者进行广泛的特征，目的是揭示响应者和非响应者表型，以预测对特定疗法的反应。拟议的应用将使Sheshadri博士能够发展出高级研究职业，该研究专注于开发新型的定量成像技术来增强阻塞性气道疾病的表型表征。