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

描述（由申请人提供）：大约有100万患有控制不充分的严重持续性哮喘的美国人具有特别高的急性加重、住院和死亡风险，并且每年每个患者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，降低其厚度和高反应性。在三个手术过程中，这种新型微创干预适用于所有3 mm及以上的气道。我们假设，超极化氙（HPLF）MRI可以识别主导患者症状的功能障碍气道的子集，并且图像引导的单次手术可以消除对非受累气道的过度治疗，最大限度地降低风险和生产力损失，降低管理该患者群体的成本，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先导性研究。所有患者都将参加三次HSP 70 MRI肺功能成像评估，以评估其通气缺陷：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分段气道与观察到的通气缺陷联系起来来识别和排名。虽然所有患者都将接受完整的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气道的指导性BT治疗，而对照组将接受治疗 按照标准顺序。 如果变化与已发表的BT试验相似，这项试点研究有足够的把握度检测一次图像引导BT治疗后生活质量（QoL）较基线的变化。然而，我们寻求从我们的数据中更好地了解BT反应的生物预测因子。我们假设，HSP 70 MRI将提供一个比QoL更定量的哮喘严重程度分级指标来评估BT。本研究的一个重要目的是评估哮喘疾病严重程度的HSP 70 MRI生物标志物，包括一组四张图像，用于确定平均气道阻塞、支气管扩张剂反应性以及这些指标随时间的变化。 以HSP 70 MRI指标作为主要终点，以几个哮喘QoL指标作为次要终点，我们在研究揭盲后比较了单次图像引导BT治疗与标准三次BT治疗。进行两次比较：将单次引导BT治疗后的目标组与完整三次治疗后的对照组进行比较;并将三次治疗后的目标组与其自身改善情况进行比较，作为其自身对照。如果数据支持最有利的结果，即MRI引导的BT治疗可以减少三分之二的过度治疗，将BT成本降低一半，并获得同等的益处，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伴随诊断，HSP 70将在几年内成为FDA批准和商业可用的诊断剂。

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.