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

描述(由申请人提供)：大约100万患有严重持续性哮喘的美国人病情恶化、住院和死亡的风险特别高，每个患者每年的医疗保健负担超过12,000美元。支气管热成形术(BT)将射频加热应用于气道平滑肌，减少其厚度和高反应性。这种新型的微创介入治疗适用于所有3 mm及以上的气管，在三个手术过程中。我们假设，超极化氙气(HXE)MRI可以识别出主导患者症状的一部分功能障碍的呼吸道，而图像引导的单次治疗程序可以消除对非受累呼吸道的过度治疗，将风险和生产力损失降至最低，降低管理这一患者组的成本，并说服更多的支付者报销。我们建议对30名选择接受BT治疗的重度哮喘患者进行双盲试点研究。所有患者都将参加三次HXE MRI肺功能成像评估他们的呼吸缺陷：基线、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性气道与观察到的通风缺陷联系起来来识别和排序。虽然所有患者都将接受全程BT治疗，但其中一半患者将在第一次治疗中接受针对最有问题的呼吸道的引导BT治疗，而对照组将接受治疗 按照标准的顺序。这项先导性研究有30名受试者，如果与已发表的BT试验相似，这项先导性研究足以检测一次图像引导的BT治疗后生活质量(QOL)较基线的变化。然而，我们从我们的数据中寻求对Bt反应的生物指标的更多了解。我们假设HXE MRI将为哮喘严重程度的分级提供比QOL更定量的指标来评估BT。这项研究的一个重要目的是评估哮喘疾病严重性的HXE MRI生物标记物，该标记物包括一组确定平均气道阻塞、支气管扩张剂反应性和这些指标随时间变化的四幅图像。以HXE MRI指标为主要终点，以几个哮喘QOL指数为次要终点，我们在解盲研究后，比较了单次疗程图像引导BT治疗和标准三次BT治疗。两组比较：单次引导BT治疗后的目标组与对照组在三次治疗后进行比较；三次治疗后与自身改善情况进行比较，作为自身对照。如果数据支持最有利的结果，HXE MRI引导的BT治疗可以减少三分之二的过度治疗，将BT的成本削减一半，并实现同等的好处，那么100万美国人可以选择图像引导的BT来改善他们对严重哮喘的管理。最后，作为影像引导治疗的临床指示辅助诊断，HXE将在几年内成为FDA批准的和商业化的诊断试剂。

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.