Parametric Response Mapping (PRM) for the detection of chronic lung injury in hematopoietic cell transplant recipients

摘要 慢性肺功能障碍(CLD)是骨髓移植(BMT)的潜在严重并发症， 尤其流行于骨髓移植后发生慢性移植物抗宿主病(GVHD)的患者。这个 慢性阻塞性肺疾病的发展与20%-40%的长期存活率有关，大多数患者 只有在他们出现明显的(且可能不可逆转的)肺部病变后，才能诊断为慢性肺病。 迫切需要在慢性阻塞性肺疾病的临床病程中及早发现，在治疗可能被证明是有益的阶段。 对病人来说。参数响应映射(PRM)是一种基于计算机断层扫描(CT)的新方法 当应用于标准CT扫描时，它能够识别和量化各种肺部疾病亚型 在病人身上。这项技术最初是由密歇根医学公司在10多年前为患有 慢性阻塞性肺疾病(COPD)。在单中心和多中心试验中，PRM都有 证实了在成人骨髓移植患者中识别CLD的有效性。我们的中心假设是PRM可以 确定慢性移植物抗宿主病患者是慢性移植物抗宿主病的高危人群。我们提出了一个 成人和儿童(3岁≥)慢性移植物抗宿主病后PRM检测的观察性研究 北京时间。为了验证我们的假设，我们设定了三个具体目标。在前两部分中，我们将检查PRM值 在两个主要时间点：慢性移植物抗宿主病开始时(目标1)和慢性移植物抗宿主病开始时(目标2)，定义慢性移植物抗宿主病 根据美国国立卫生研究院的标准。在目标3中，我们将开发一个机器学习模型，该模型将结合血清学和 肺功能测试(PFT)生物标记物与PRM值，以开发一个复合生物标记物策略。vt.在.的基础上 完成我们目前的建议后，我们将建立PRM作为成人BMT患者CLD的预测因子。此外, 从儿童骨髓移植患者中获得的PRM、PFT和血清学数据将为未来提供数据库 在这一人群中进行研究。从历史上看，在儿童患者中识别CLD的能力一直依赖于PFT， 从技术上讲，在幼儿中进行PFT具有挑战性。PRM作为慢性阻塞性肺疾病诊断指标的应用 在儿科骨髓移植患者中，这将是这一提议的一大进步。最后，我们的提案采用了我们的PRM 在成人中推进方法学，使我们能够研究成人骨髓移植受者肺部疾病的轨迹 慢性移植物抗宿主病，以及慢性移植物抗宿主病的发病。

ABSTRACT Chronic lung dysfunction (CLD) is a potentially severe complication of bone marrow transplantation (BMT), particularly prevalent in patients who develop chronic graft versus host disease (GVHD) post-BMT. The development of CLD is associated with a 20%-40% long term survival rate, with the majority of patients diagnosed with CLD only after they have developed significant (and potentially irreversible) lung pathology. There is a critical need to identify CLD earlier in its clinical course, at a stage when treatment may prove beneficial to patients. Parametric response mapping (PRM) is a novel computed tomography (CT) based methodology that when applied to standard CT scans is capable of identifying and quantifying a variety of lung disease subtypes in patients. This technology was initially developed at Michigan Medicine over 10 years ago for patients with chronic obstructive pulmonary disease (COPD). In both single center and multicenter trials, PRM has demonstrated efficacy for the identification of CLD in adult BMT patients. Our central hypothesis is that PRM can identify patients with chronic GVHD who are at high risk for the development of CLD. We propose an observational study to examine PRM in adult and pediatric subjects (≥ 3 years in age) with chronic GVHD post- BMT. To test our hypothesis, we have established 3 specific aims. In the first two, we will examine PRM values at two main time points: at the onset of chronic GVHD (Aim 1) and at the onset of CLD (Aim 2), with CLD defined by standard NIH criteria. In Aim 3, we will develop a machine learning model that will incorporate serologic and pulmonary function test (PFT) biomarkers with PRM values to develop a composite biomarker strategy. Upon completion of our current proposal, we will establish PRM as a predictor of CLD in adult BMT patients. In addition, the PRM, PFT, and serologic data obtained from pediatric BMT patients will provide a data bank for future research in this population. Historically, the ability to identify CLD in pediatric patients has been PFT-dependent, with PFTs technically challenging to conduct in young children. The use of PRM as a diagnostic indicator of CLD in pediatric BMT patients will be a major advance of this proposal. Finally, our proposal takes our PRM methodology forward in adults, allowing us to study the trajectory of lung disease in adult BMT recipients with chronic GVHD, and following the onset of CLD.