A Natural History Study of Novel Biomarkers in Pulmonary Arterial Hypertension

PAH（即第 1 类 PAH）是一种与生存率低相关的罕见疾病。 1) 遗传易感性和 2) 引发肺血管损伤的触发刺激（二次打击假说）引起的内皮功能障碍似乎在 PAH 的发病机制和进展中发挥着核心作用。 炎症似乎会导致这种功能失调的内皮表型，在遗传易感的特发性 PAH (IPAH) 患者和疾病相关 PAH 患者中传播损伤和修复的循环。 然而，尽管越来越多的证据表明 PAH 患者存在血管炎症，但对该过程的时间演变及其对右心室 (RV) 和肺血管重塑的贡献仍缺乏详细的表型研究。 该方案最初于 2012 年 10 月获得 NHLBI IRB 批准。随后，在合作地点寻求并获得了 IRB 批准，并且到 2013 年夏季，所有机构都进行了各种修订。目前正在从多个地点收到推荐。 迄今为止，本研究已筛选了 51 名受试者，其中 14 名已入组。 我们假设，详细描述 PAH 中血管炎症和神经激素激活的时间演变及其对 RV 和肺血管功能的影响将为传统的疾病严重程度测量增加预后价值，并为未来研究提出新的治疗靶点。

PAH (i.e. Group 1 PAH) is a rare disorder associated with poor survival. Endothelial dysfunction resulting from 1) genetic susceptibility, and 2) a triggering stimulus that initiates pulmonary vascular injury, the two-hit hypothesis, appears to play a central role both in the pathogenesis and progression of PAH. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic PAH (IPAH) and patients with disease-associated PAH. However, despite mounting evidence of vascular inflammation in patients with PAH, detailed phenotypic studies are lacking on the temporal evolution of this process and its contribution to right ventricular (RV) and pulmonary vascular remodeling. The protocol was initially approved by the NHLBI IRB in October 2012. Subsequently IRB approval was sought and obtained at collaborating sites and various amendments were brought into alignment at all institutions by summer 2013. Referrals are being received from multiple sites. To date 51 subjects have been screened for this study and 14 have been enrolled. We hypothesize that a detailed characterization of the temporal evolution of vascular inflammation and neurohormonal activation in PAH and its impact on RV and pulmonary vascular function will add prognostic value to traditional measures of disease severity and suggest novel therapeutic targets for future research.