Coupling MRI-Derived Ventilation with Computational Models to Assess Inhaled Aerosol Treatment Feasibility in Severe Asthmatic Adults

将 MRI 衍生通气与计算模型相结合，评估吸入气雾剂治疗成人严重哮喘的可行性

• 批准号: 9441318
• 负责人: Jessica M Oakes
• 金额: $ 12.95万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9441318
• 关键词: Adult; Aerosols; Affect; Airway Resistance; Alternative Therapies; Anatomy; Asthma; Breathing; Caring; Characteristics; Chest; Chronic; Clinical; Computer Simulation; Computing Methodologies; Coupling; Data; Data Set; Databases; Defect; Deposition; Development; Disease; Disease Management; Disease Progression; Dose; Drug Delivery Systems; Economic Burden; Environmental air flow; Exhalation; Frequencies; Funding; Future; Gases; Geometry; Goals; Gravitation; High Resolution Computed Tomography; Inhalators; Injectable; Lead; Lobar; Location; Lung; Magnetic Resonance Imaging; Maintenance; Maps; Measures; Medical Imaging; Methodology; Modeling; Morphology; National Heart, Lung, and Blood Institute; Oral; Pathology; Patients; Peripheral; Pharmaceutical Preparations; Phenotype; Physiological; Program Research Project Grants; Property; Research; Resistance; Rest; Severities; Severity of illness; Site; Structure; Techniques; Testing; Therapeutic; United States; United States National Institutes of Health; Variant; X-Ray Computed Tomography; airway hyperresponsiveness; alternative treatment; asthmatic; asthmatic patient; base; cohort; computer framework; constriction; cost; disorder control; dosimetry; effective therapy; experimental study; insight; particle; patient oriented; programs; pulmonary function; respiratory; respiratory smooth muscle; standard care; treatment strategy

Asthma is a chronic airway disorder that impacts 22.9 million people in the United States and causes a substantial economic burden. Asthma attacks (exacerbation) are triggered by stimulation of chronically inflamed airways and hyper responsive airway smooth muscle, leading to airway constriction and obstructed airflow. Reducing the frequency of exacerbations is the primary goal of asthma disease management. Severe asthma is especially challenging to treat, as this cohort of patients (~15%) does not respond well to inhaled therapeutics, resulting in significantly higher heath care costs compared to patients with milder disease severity. One of the keys to asthma management is to identify early which set of patients may benefit from alternative treatment strategies. However assessing dosimetry experimentally is not currently feasible especially on a patient-­to-­patient basis. Computational models, on the other hand, provide a unique opportunity to uncover anatomical and physiological features that lead to inadequate dosing. Thus, the main goal of this R21 proposal is to determine which set of patients may benefit from alternative treatment strategies. To do this, existing datasets collected from as part of the NIH funded Severe Asthma Research Program (SARP) will be incorporated to study inhaled medications. A subset of this study includes hyperpolarized 3He ventilation and high-­ resolution CT images, thereby providing the opportunity to couple patient-­specific anatomy and ventilation distribution with advanced modeling techniques. Incorporation of segmental-­level ventilation defects percent (VDP) will enable accurate ventilation distributions to be incorporated into the respiratory in silico models and for peripheral delivery to be correlated with the heterogeneous ventilation. With this existing dataset, we will test our hypothesis that abnormal drug delivery concentrations are correlated to airway morphometric features which may be identified directly from CT images. Within the scope of this proposal, we will make key advances in determining which set of patients would benefit from alternative treatment strategies (e.g. systemic medications) because of inadequate peripheral airway delivery.

哮喘是一种慢性气道疾病，影响着美国 2290 万人，并造成巨大的经济负担。 哮喘发作（加重）是由于刺激慢性发炎的气道和高反应性气道平滑肌而引发的，导致气道收缩和气流受阻。减少哮喘发作频率是哮喘疾病管理的首要目标。严重哮喘的治疗尤其具有挑战性， 因为这组患者（~15%）对吸入疗法反应不佳，导致 与疾病严重程度较轻的患者相比，医疗费用明显更高。 之一 哮喘管理的关键是尽早确定哪些患者可能受益 替代治疗策略。然而，目前还没有通过实验评估剂量测定 特别是在患者对患者的基础上是可行的。另一方面，计算模型 提供了一个独特的机会来揭示导致的解剖和生理特征 剂量不足。 因此，该 R21 提案的主要目标是确定哪一组患者 可能会受益于替代治疗策略。 为此，从以下位置收集的现有数据集 NIH 资助的严重哮喘研究计划 (SARP) 的一部分将被纳入研究 吸入药物。这项研究的一个子集包括超极化 3He 通气和高 分辨率 CT 图像，从而提供结合患者特定解剖结构和 采用先进建模技术的通风分布。合并分段级别 通风缺陷百分比 (VDP) 将能够纳入准确的通风分布 进入计算机模拟呼吸系统并与外周输送相关 异质通风。利用这个现有的数据集，我们将检验我们的假设：异常 药物输送浓度与气道形态特征相关，这可能是 直接从CT图像中识别。 在本提案的范围内，我们将取得重大进展 确定哪组患者将从替代治疗策略中受益（例如 全身药物），因为外周气道输送不足。