A Natural History Study of Novel Biomarkers in Pulmonary Arterial Hypertension

PAH（即第1组PAH）是一种与生存率差相关的罕见疾病。 由1）遗传易感性和2）引发肺血管损伤的触发刺激（两次打击假说）导致的内皮功能障碍似乎在PAH的发病机制和进展中发挥核心作用。 炎症似乎驱动这种功能障碍的内皮表型，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周期。 然而，尽管有越来越多的证据表明PAH患者存在血管炎症，但缺乏关于该过程的时间演变及其对右心室（RV）和肺血管重塑的贡献的详细表型研究。 该方案最初于2012年10月获得NHLBI IRB批准。随后，在合作研究中心寻求并获得了IRB批准，并在2013年夏季之前在所有机构进行了各种修订。 正在从多个站点接收推荐。 迄今为止，本研究筛选了51例受试者，14例入组。 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，并为未来的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.