Hasan Jamal, Beharry Kay D, Valencia Arwin M, Strauss Arthur, Modanlou Houchang D
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of California Irvine Medical Center, 101 The City Drive South, Route 81, Building 56, Suite 600, Orange, CA 92868, USA.
Pediatrics. 2009 Jun;123(6):1541-7. doi: 10.1542/peds.2008-1670.
We tested the hypothesis that soluble vascular endothelial growth factor receptors are involved in the development of bronchopulmonary dysplasia/chronic lung disease.
Neonates with a birth weight of < or =1500 g and/or < or =30 weeks' gestation, with respiratory failure, requiring O(2) and mechanical ventilation within 24 hours, were eligible. Tracheal aspirate fluid samples were collected from 65 neonates before surfactant and/or assisted mechanical ventilation (baseline), at 3 and 7 days after birth, and weekly thereafter until extubation. Samples were analyzed for total vascular endothelial growth factor, soluble vascular endothelial growth factor receptor 1 and 2 levels and compared in infants with bronchopulmonary dysplasia/chronic lung disease (n = 31) versus those with no bronchopulmonary dysplasia/chronic lung disease (n = 34).
Mean gestational age and birth weight were lower in infants with bronchopulmonary dysplasia/chronic lung disease. At baseline, vascular endothelial growth factor levels in the tracheal aspirate fluid were significantly lower, whereas soluble vascular endothelial growth factor receptor 1 levels were higher in the bronchopulmonary dysplasia/chronic lung disease infants compared with infants with no bronchopulmonary dysplasia/chronic lung disease. Vascular endothelial growth factor levels progressively increased from baseline to 4 weeks in all of the infants developing bronchopulmonary dysplasia/chronic lung disease. Conversely, soluble vascular endothelial growth factor receptor 1 declined in both groups from baseline to 5 weeks of age. Similarly, soluble vascular endothelial growth factor receptor 2 declined from baseline to 5 weeks in the control infants, but there were significant increases at 3 and 4 weeks in infants developing bronchopulmonary dysplasia/chronic lung disease.
We speculate that low vascular endothelial growth factor levels in tracheal aspirate fluid, concurrent with elevated soluble vascular endothelial growth factor receptor 1 levels on the first day of life, are biological markers for the development of bronchopulmonary dysplasia/chronic lung disease in very low birth weight infants requiring O(2) and assisted mechanical ventilation.
我们检验了可溶性血管内皮生长因子受体参与支气管肺发育不良/慢性肺病发生发展的这一假设。
出生体重≤1500克和/或胎龄≤30周、出现呼吸衰竭且在24小时内需要吸氧及机械通气的新生儿符合入选标准。在65例新生儿使用表面活性剂和/或辅助机械通气前(基线)、出生后3天和7天以及此后每周直至拔管时收集气管吸出液样本。分析样本中的总血管内皮生长因子、可溶性血管内皮生长因子受体1和2水平,并在发生支气管肺发育不良/慢性肺病的婴儿(n = 31)与未发生支气管肺发育不良/慢性肺病的婴儿(n = 34)之间进行比较。
发生支气管肺发育不良/慢性肺病的婴儿平均胎龄和出生体重较低。在基线时,与未发生支气管肺发育不良/慢性肺病的婴儿相比,发生支气管肺发育不良/慢性肺病的婴儿气管吸出液中的血管内皮生长因子水平显著较低,而可溶性血管内皮生长因子受体1水平较高。在所有发生支气管肺发育不良/慢性肺病的婴儿中,血管内皮生长因子水平从基线至4周逐渐升高。相反,两组中可溶性血管内皮生长因子受体1从基线至5周龄均下降。同样,对照婴儿中可溶性血管内皮生长因子受体2从基线至5周下降,但发生支气管肺发育不良/慢性肺病的婴儿在3周和4周时有显著升高。
我们推测,气管吸出液中血管内皮生长因子水平较低,同时出生第一天可溶性血管内皮生长因子受体1水平升高,是需要吸氧及辅助机械通气的极低出生体重儿发生支气管肺发育不良/慢性肺病的生物学标志物。