Single-session bronchial thermoplasty for severe asthmatics guided by HXe MRI

HXe MRI 引导下的单次支气管热成形术治疗严重哮喘患者

• 批准号: 8607367
• 负责人: Iulian Constantin Ruset
• 金额: $ 61.7万
• 依托单位: XEMED, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8607367
• 关键词: Accident and Emergency department; Accounting; Aftercare; American; Ancillary Study; Asthma; Biological; Biological Markers; Bronchodilation; Bronchodilator Agents; Bronchoscopy; Cessation of life; Characteristics; Chest; Clinical; Clinical Trials; Companions; Computer software; Control Groups; Data; Data Analyses; Defect; Diagnostic; Diagnostic Imaging; Double-Blind Method; Enrollment; Environmental air flow; FDA approved; Functional Imaging; Goals; Guidelines; Healthcare; Heating; Hospitalization; Image; Image Analysis; Individual; Inferior; Intervention; Life; Link; Lung; MRI Scans; Magnetic Resonance Imaging; Maps; Measures; Methods; Metric; Observational Study; Obstruction; Outcome; Patients; Phase; Pilot Projects; Procedures; Productivity; Publishing; Quality of life; Reader; Recovery; Recruitment Activity; Refractory; Regimen; Risk; Scheme; Sequence Analysis; Series; Severities; Severity of illness; Small Business Innovation Research Grant; Smooth Muscle; Symptoms; Therapeutic; Therapeutic procedure; Thick; Time; TimeLine; Treatment Protocols; Universities; Variant; Visit; Washington; X-Ray Computed Tomography; Xenon; airway obstruction; base; blind; care burden; cost; high risk; image guided therapy; improved; indexing; innovation; minimally invasive; novel; prospective; radiofrequency; respiratory smooth muscle; response; time interval; treatment planning

DESCRIPTION (provided by applicant): Roughly one million Americans with inadequately controlled severe persistent asthma have a particularly high risk of exacerbations, hospitalizations, and death, and account for a per-patient health care burden exceeding $12,000 annually. Bronchial thermoplasty (BT) applies radiofrequency heating to airway smooth muscle reducing its thickness and hyper-reactivity. This novel minimally invasive intervention is applied to all airways 3mm and larger over the course of three procedures. We hypothesize that hyperpolarized xenon (HXe) MRI could identify a subset of dysfunctional airways that dominate the patient's symptoms, and that an image-guided single-session procedure could eliminate overtreatment of non-involved airways, minimize risk and lost productivity, reduce costs of managing this patient group, and convince more payers to reimburse. We propose a double-blind pilot study of thirty patients with severe asthma electing to undergo BT. All patients will participate in three HXe MRI pulmonary functional imaging evaluations of their ventilation defects: at baseline, after their first BT treatment and recovery, and after their final BT treatmet and recovery. Existing and new software methods will identify and rank problematic segmental airways by linking them with the observed ventilation defects. While all patients will receive the full course of BT treatment, half of them will receive a guided BT treatment targeting the most problematic airways in their first treatment session while the control group will receive treatment following the standard sequence. With thirty subjects, this pilot study is adequately powered to detect a change in Quality of Life (QoL) from baseline after one image-guided BT treatment, if changes are similar to published BT trials. We seek, however, greater understanding of biopredictors of BT response from our data. We hypothesize that HXe MRI will provide a metric for grading asthma severity more quantitative than QoL for evaluating BT. An important aim of this study is to evaluate this HXe MRI biomarker for asthma disease severity that includes a set of four images that determine average airway obstruction, bronchodilator reactivity, and variation of these metrics with time. With the HXe MRI metric as our primary endpoint and several asthma QoL indices as secondary end-points, we compare the single session image-guided BT treatment to the standard three-session BT treatment after unblinding the study. Two comparisons are performed: the target group after the single-session guided BT treatment will be compared with the control group after the full three sessions; and will be compared with their own improvement after three sessions, serving as their own controls. If data support the most favorable outcome, that HXe MRI guided BT treatment can reduce overtreatment by two-thirds, cut BT costs in half, and achieve an equivalent benefit, then one million Americans could elect image-guided BT to improve their management of severe asthma. Finally, as a clinically-indicated companion diagnostic for an image-guided therapy, HXe would become an FDA-approved and commercially available diagnostic agent within a few years.

描述（由申请人提供）：大约100万患有控制不充分的严重持续性哮喘的美国人有特别高的恶化，住院和死亡风险，并且每个患者每年的医疗负担超过12,000美元。支气管热成形术（BT）应用射频加热气道平滑肌减少其厚度和高反应性。这种新颖的微创干预在三次手术过程中适用于所有3mm及更大的气道。我们假设，超偏光氙气（HXe） MRI可以识别出主导患者症状的功能失调气道子集，并且图像引导的单次手术可以消除对非受损伤气道的过度治疗，最大限度地降低风险和效率损失，降低管理该患者组的成本，并说服更多的付款人进行报销。我们建议对30例选择接受BT治疗的严重哮喘患者进行双盲试点研究，所有患者将参加三次HXe MRI通气缺陷肺功能成像评估：基线时，首次BT治疗和恢复后，以及最终BT治疗和恢复后。现有的和新的软件方法将通过将有问题的节段气道与观察到的通风缺陷联系起来来识别和排名。虽然所有患者都将接受整个疗程的BT治疗，但其中一半患者将在第一次治疗时接受针对问题气道的引导BT治疗，而对照组将接受治疗