Supplementary Material for: Plasma Endothelin-1 and Vascular Endothelial Growth Factor Levels and Their Relationship to Hemodynamics in Idiopathic Pulmonary Fibrosis

Background: Pulmonary hypertension (PH) is associated with a poor prognosis in idiopathic pulmonary fibrosis (IPF). Endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) are important in both fibrosis and vascular remodeling. Objectives: We sought to determine the relationship between ET-1 and VEGF levels and hemodynamics in patients with IPF. We hypothesized that higher levels of ET-1 and VEGF would be associated with higher pulmonary artery pressures (PAP) and pulmonary vascular resistance (PVR) in patients with IPF. Methods: We performed a cross-sectional analysis of 52 adults with IPF enrolled in a prospective cohort with available clinical data, platelet-free plasma, and hemodynamics. ET-1 and VEGF levels were measured via immunoassay. The associations of ET-1 and VEGF with PAP and PVR were examined using generalized additive models adjusted for age, gender, race/ethnicity, and forced vital capacity (% predicted). Results: Sixteen of 52 (30.8%) had PH (mean PAP ≥25 mm Hg). After multivariable adjustment, higher ET-1 levels were significantly associated with higher systolic (p = 0.01), diastolic (p = 0.02), and mean (p = 0.01) PAP and possibly higher PVR (p = 0.09). There were no significant associations between VEGF levels and hemodynamics. Conclusions: Higher levels of ET-1 were associated with higher PAP and possibly higher PVR in participants with IPF. In a subgroup of patients, ET-1 may be a contributor to pulmonary vascular disease burden in IPF.

背景：肺动脉高压（Pulmonary Hypertension, PH）与特发性肺纤维化（Idiopathic Pulmonary Fibrosis, IPF）患者的不良预后密切相关。内皮素-1（Endothelin-1, ET-1）与血管内皮生长因子（Vascular Endothelial Growth Factor, VEGF）在肺纤维化及血管重构过程中均发挥重要作用。
研究目的：本研究旨在明确IPF患者体内ET-1、VEGF水平与血流动力学指标之间的关联，并提出假说：IPF患者体内更高水平的ET-1与VEGF，将对应更高的肺动脉压（Pulmonary Artery Pressure, PAP）与肺血管阻力（Pulmonary Vascular Resistance, PVR）。
研究方法：本研究对纳入前瞻性队列的52名成人IPF患者开展横断面分析，所有受试者均拥有可用的临床数据、无血小板血浆标本及血流动力学检测结果。采用免疫测定法检测ET-1与VEGF水平，通过校正了年龄、性别、种族/族裔以及预计值百分比用力肺活量（forced vital capacity % predicted）的广义加性模型（Generalized Additive Model），分析ET-1、VEGF与PAP、PVR之间的关联。
研究结果：52名受试者中16名（30.8%）合并PH（平均PAP≥25mmHg）。经多变量校正后，更高的ET-1水平与更高的收缩期PAP（p=0.01）、舒张期PAP（p=0.02）及平均PAP（p=0.01）显著相关，同时可能与更高的PVR存在关联（p=0.09）。而VEGF水平与血流动力学指标未观察到显著关联。
研究结论：IPF患者体内更高的ET-1水平与更高的PAP及可能更高的PVR相关。在部分患者亚组中，ET-1或可成为IPF患者肺血管疾病负荷的潜在影响因素。