Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Intensive Care, Maastricht University Medical Center+, Maastricht University, Maastricht, The Netherlands.
Am J Physiol Lung Cell Mol Physiol. 2023 Jan 1;324(1):L38-L47. doi: 10.1152/ajplung.00185.2022. Epub 2022 Nov 8.
Pulmonary edema is a central hallmark of acute respiratory distress syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to alveolar-capillary permeability but their differential contribution to pulmonary edema development remains understudied. Plasma levels of surfactant protein-D (SP-D), soluble receptor for advanced glycation end products (sRAGE), and angiopoietin-2 (Ang-2) were measured in a prospective, multicenter cohort of invasively ventilated patients. Pulmonary edema was quantified using the radiographic assessment of lung edema (RALE) and global lung ultrasound (LUS) score. Variables were collected within 48 h after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema. In 362 patients, higher SP-D, sRAGE, and Ang-2 concentrations were significantly associated with higher RALE and global LUS scores. After stratification by ARDS subgroups (pulmonary, nonpulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, whereas sRAGE and Ang-2 showed less consistent associations throughout the subgroups. In a multivariable analysis, SP-D levels were most strongly associated with pulmonary edema when combined with sRAGE (RALE score: β = 6.79 units/log10 pg/mL, β = 3.84 units/log10 pg/mL, = 0.23; global LUS score: β = 3.28 units/log10 pg/mL, β = 2.06 units/log10 pg/mL, = 0.086), whereas Ang-2 did not further improve the model. Biomarkers of epithelial injury and endothelial dysfunction were associated with pulmonary edema in invasively ventilated patients. SP-D and sRAGE showed the strongest association, suggesting that epithelial injury may form a final common pathway in the alveolar-capillary barrier dysfunction underlying pulmonary edema.
肺水肿是急性呼吸窘迫综合征（ARDS）的主要特征。内皮功能障碍和上皮损伤导致肺泡毛细血管通透性增加，但它们对肺水肿发展的不同贡献仍研究不足。在一项前瞻性、多中心的有创通气患者队列研究中，测量了表面活性蛋白-D（SP-D）、晚期糖基化终产物可溶性受体（sRAGE）和血管生成素-2（Ang-2）的血浆水平。使用放射影像评估肺水肿（RALE）和整体肺超声（LUS）评分来量化肺水肿。变量在插管后 48 小时内收集。线性回归用于检查生物标志物与肺水肿的相关性。在 362 名患者中，较高的 SP-D、sRAGE 和 Ang-2 浓度与较高的 RALE 和整体 LUS 评分显著相关。在按 ARDS 亚组（肺、非肺、COVID、非 COVID）分层后，SP-D 水平与肺水肿的正相关性仍然存在，而 sRAGE 和 Ang-2 在整个亚组中的相关性不太一致。在多变量分析中，当 SP-D 水平与 sRAGE 结合时，与肺水肿的相关性最强（RALE 评分：β=6.79 单位/对数 10 pg/mL，β=3.84 单位/对数 10 pg/mL，P=0.23；整体 LUS 评分：β=3.28 单位/对数 10 pg/mL，β=2.06 单位/对数 10 pg/mL，P=0.086），而 Ang-2 并不能进一步改善模型。上皮损伤和内皮功能障碍的生物标志物与有创通气患者的肺水肿相关。SP-D 和 sRAGE 显示出最强的相关性，表明上皮损伤可能是导致肺水肿的肺泡毛细血管屏障功能障碍的最终共同途径。
