Distinguishing Phenotypes of Pulmonary Hypertension in Patients with Connective Tissue Disease-related Interstitial Lung Disease

项目总结 肺动脉高压(PH)是一种病因众多但治疗有限的高度病态疾病。好处是- 仅已知可行的药物对患有非常特殊形式的PH的患者安全有效。最近， 一种吸入性药物，曲普替尼，被批准用于治疗与间质性肺疾病(PH- ILD)。大多数PH-ILD研究要么专注于特发性肺纤维化患者，要么将ILD作为一种 包含性诊断。然而，各种形式的ILD在其潜在的病理生理学和房颤方面是不同的。 受感染的患者群体。结缔组织病相关的ILD(CTD-ILD)是一种研究较少的ILD 这往往会影响年轻的、不同种族的女性患者。PH与CTD-ILD的交集是粒子-ILD。 巨大的挑战性，因为肺高压可能通过纤维化诱导的肺血管消融或从 CTD慢性炎症引起的血管内功能障碍。在这个时候，确定哪种机制 单个CTD-ILD患者的PH由临床医生自行决定，他们还必须决定 根据他们的决定使用的治疗方法。这些决定通常是由对 胸部影像所见的纤维化程度(例如，计算机断层扫描[CT])，限制呼吸的严重程度 在肺功能测试(PFT)中测量的缺陷，以及有创性血流动力学测量。在这 建议，我将使用基于CT和PFT的严重程度分期系统，该系统已在硬化症患者中得到验证。 DERMA ILD，将CTD-ILD和PH患者分为实质表型或血管表型。 当我将这个系统应用于约翰·霍普金斯公共卫生中心登记处的20名患者时，其中35%的患者 重新分类，并接受了与其表型不一致的治疗。来调查这些事件的影响 初步发现，我将利用约翰霍普金斯PH、ILD和肌炎中心的登记来进行表型分析 CTD-ILD相关PH患者(CTD-ILD-PH)。我的首要目标是确定CTD-ILD-PH的比例 具有实质和血管表型的患者，并比较表型之间的疾病严重程度 在确诊的时候。为此，我将比较当时收集的各种疾病严重程度的衡量标准 目前和未来在我们登记登记的患者的PH诊断。这些措施将包括 全球和特定症状的生活质量问卷、6分钟步行距离、世卫组织职能级别以及 通过超声心动图、血清NT-Pro-BNP水平和右心导管术评估血流动力学。 第二，比较表型一致的CTD-ILD-PH患者的临床结果 与那些接受表型不协调治疗的人相比，我会比较临床措施的差异。 在四到六个月的PH治疗之前和之后，上面都写着。这项研究的结果将为 告知未来针对CTD-ILD实质和血管表型患者的PH治疗研究 并为未来的K-Level奖项奠定坚实的基础。

PROJECT SUMMARY Pulmonary hypertension (PH) is a highly morbid disease with numerous causes but limited therapies. The avail- able medications are only known to be safe and effective for patients with very specific forms of PH. Recently, an inhaled medication, treprostinil, was approved for the treatment of PH related to interstitial lung disease (PH- ILD). Most PH-ILD studies have either focused on patients with idiopathic pulmonary fibrosis or ILD as an all- inclusive diagnosis. However, the various forms of ILD are distinct in their underlying pathophysiology and af- fected patient populations. Connective tissue disease-related ILD (CTD-ILD) is an understudied form of ILD which tends to affect young, ethnically diverse, female patients. The intersection of PH and CTD-ILD is particu- larly challenging as the PH may arise through fibrosis-induced ablation of pulmonary blood vessels or from endovascular dysfunction driven by the chronic inflammation of CTD. At this time, determining which mechanism underlies an individual CTD-ILD patient’s PH is left to the discretion of clinicians who must also decide which treatments to use based on their decision. These decisions are usually guided by subjective assessments of the degree of fibrosis seen on chest imaging (e.g., computed tomography [CT]), the severity of restrictive ventilatory defect measured during pulmonary function testing (PFT), and invasive hemodynamic measurements. In this proposal, I will use a CT- and PFT-based severity staging system which was validated in patients with sclero- derma ILD, to classify patients with CTD-ILD and PH as having either a parenchymal or vascular phenotype. When I applied this system to 20 patients in the Johns Hopkins PH Center Registry, 35% of these patients were reclassified and had received therapies discordant with their phenotype. To investigate the implications of these preliminary findings, I will leverage the Johns Hopkins PH, ILD, and Myositis Centers’ registries to phenotype patients with CTD-ILD-related PH (CTD-ILD-PH). My first aim is to determine the proportion of CTD-ILD-PH patients with parenchymal and vascular phenotypes and compare disease severity between phenotypes at the time of diagnosis. For this aim, I will compare various measures of disease severity collected at the time of PH diagnosis for patients currently and prospectively enrolled in our registries. These measures will include global and symptom-specific quality of life questionnaires, 6-minute walk distances, WHO functional class, and hemodynamic assessments by echocardiography, serum NT-pro-BNP levels, and right heart catheterization. Second, to compare the clinical outcomes of CTD-ILD-PH patients who receive phenotype-concordant therapy with those who receive phenotype-discordant therapy, I will compare the clinical measures de- scribed above before and after four to six months of PH therapy. Results from this study will provide data to inform future studies of PH therapies for patients with the parenchymal and vascular phenotypes of CTD-ILD- PH and serve as a strong foundation for a future K-level award.