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障碍，在美国，有2290万人的经济负担是长期发炎的时机。 。 由于这种患者队列（约15％）对吸入theraled Therapeutics的反应不佳，从而导致 与疾病严重性严重的患者相比，护理护理成本明显更高。 哮喘管理的关键是尽早确定哪种患者可能会从中受益 替代治疗策略。 另一方面 提供独特的机会，以发现导致解剖学和生理特征 因此，剂量不足。 可以从替代信任策略中受益。 NIH资助的严重哮喘研究计划（SARP）的一部分将不在研究 吸收药物。 分辨率CT图像，从而为夫妇特定于患者的解剖结构和Andn提供了机会 带有高级建模技术的通风分布 通风缺陷百分比（VDP）将使准确的通风能够合并 在计算机模型中进入呼吸道，并与外围 异构通风。 药物输送浓度与气道形态计量特征相关 直接从CT图像中确定。 在确定哪一组患者将受益于替代信任策略（例如 系统性药物）由于外围气道输送不足。