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.

哮喘是一种慢性呼吸道疾病，在美国有2290万人受到影响，并造成巨大的经济负担。哮喘发作(加重)是由刺激慢性炎症的呼吸道和高反应性的呼吸道平滑肌引发的，导致呼吸道狭窄和气流受阻。减少哮喘发作的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， 由于这群患者(约15%)对吸入疗法反应不佳，导致 与病情较轻的患者相比，医疗保健成本明显更高。其中之一 哮喘管理的关键是及早确定哪组患者可能受益 替代治疗策略。然而，目前还没有通过实验来评估剂量学。 尤其是在病人对病人的基础上是可行的。另一方面，计算模型， 提供了一个独特的机会来发现导致 剂量不足。因此，该R21提案的主要目标是确定哪组患者 可能受益于替代治疗策略。为此，从AS收集的现有数据集 NIH资助的重症哮喘研究计划(SARP)的一部分将被纳入研究 吸入的药物。这项研究的一个子集包括超极化的3He通风和高密度 分辨率CT图像，从而提供了将患者特定的解剖和 通风分布采用先进的建模技术。分段级别的并入 通风缺陷百分比(VDP)将能够纳入准确的通风分布 在矽肺模型中进入呼吸，并将外周分娩与 异质通风。使用这个已有的数据集，我们将测试我们的假设 给药浓度与呼吸道形态特征相关，可能是 直接从CT图像中识别出来。在这项提议的范围内，我们将取得关键进展 在确定哪组患者将受益于替代治疗策略(例如 全身用药)，因为外周呼吸道输送不足。