Clinical Research On Angiopoietins In Acute Lung Injury Of Children

Clinical Research on Angiopoietins in Acute Lung Injury of Children Background:Acute lung injury(ALI) still enjoys a high mortality in children severe case. Currently,it is believed that ALI is the extensive and excessive inflammatory reaction of the lung after strikes such as serious infection,trauma,shock,massive blood transfusion,high-dose infusion.A certain degree of pulmonary microvascular endothelial cell(EC) injury exists in ALI regardless of the protopathy and the break of the integrity of pulmonary microvascular EC is a necessary factor for pulmonary interstitial edema.Angiopoietinl(Ang1),targeting at EC,performs functions like anti-apoptosis,anti-inflammation,maintaining vessel stability and anti-vessel leakage etc,and consequently has potential effects in ALI prevention and reparation.Ang2,a natural antagonist of Ang1,could destroy the vascular integrity and the intercellular connection between EC.It has been shown in previous studies that the blood level of Ang2 is related to the severity and mortality of ALI.Objective:To provide theoretical basis for clinical treatment of ALI via observing the changes of Ang1,Ang2 level in pediatric patients with ALI and analyzing the relationship with severity of ALI.Methods:68 pediatric patients in Children's Hospital of Fudan University admitted from October 1,2008 to January 31,2009 were enrolled in this study.24 cases who met ALI diagnostic criteria composed by Respiration Disease Association of Chinese Medical Association were allocated into ALI study group(male 17 cases,female 7 cases,average age 17.5±6.4 month);44 non-severe cases were allocated into control group,which include 22 cases in pneumonia control group(male 13 cases,female 9 cases,average age 17.77±4.74m) and 22 cases in non-pulmonary disease control group who had no disease except for congenital deformity in urinary system and no urinary inflammation or other diseases were detected in pre-surgery examination (male 22 cases,average age 29.5±3.71m).Patients with cancer or chronic lung diseases should be excluded from this study.For the study group,the values including PRISM score and blood gas analysis were observed upon diagnosis of ALI(Day0) and the serum level of Ang1,Ang2,SP-A were measured through blood sample collection on Day0,Day3,Day7.For the control group,blood samples were collected on the day of hospitalization to measure the serum level of Ang1,Ang2.Serum level of Ang1,Ang2,SP-A were tested by ELISA.The medical records of all the patients, collected from the library,were entered into excel 2003 software for further analysis. Statistics are performed by ANOVA,t-test and linear correlation,using SPSS13.0 software.Result:1) There is no significant difference among ALI group,pneumonia control group and non-pulmonary disease control group on gender and age(P= 0.642,P=0.185).2) Significant difference was detected in the level of Ang1,Ang2 and Ang1/Ang2 on Day 0 between ALI group upon diagnosis of ALI(24.63±2.98ng/ml, 34.15±1.99ng/ml,0.789±0.11 ng/ml) and the pneumonia control group(36.81±2.94 ng/ml,27.61±1.94 ng/ml,1.88±0.47 ng/ml) or non-pulmonary disease control group (38.57±2.81ng/ml,27.44±1.89ng/ml,1.82±0.38 ng/ml).(P=0.002,0.023,0.042)3) In ALI group,the level of Ang1 in patients with CRP≥100 showed no significant difference with that in patients with CRP＜100(21.15±5.26ng/ml; 14.39±2.38ng/ml,P=0.198);the level of Ang2 in patients with CRP≥100 was significantly higher than that in patients with CRP＜100(45.07±2.82ng/ml, 34.44±2.08ng/ml,P=0.014).4) No significant difference is detected in the level of either Ang2 or Ang1 between ALI patients treated with and those not treated with mechanical ventilation (35.89±2.73ng/ml;38.52±2.81ng/ml,P=0.51).5) The Ang2 level in ALI patients with P/F≤250 was significantly higher than that in ALI patients with P/F＞250(40.77±1.95ng/ml,29.75±3.04ng/ml,P=0.005).6) Positive correlation was determined between serum Ang2 level and serum SP-A level in ALI group(P=0.000,r_s=0.67).7) Positive correlation was determined between PRISM score and serum Ang2 level in ALI group(P=0.03,r_s =0.443).8) No statistical difference was detected in the changes of Ang1 or Ang2 level on Day0,Day3,and Day7 in 13 cases of ALI patients treated with mechanical ventilation.Conclusions:1) The serum level of Ang1 significantly decreased,while Ang2 level prominently increased and consequently the Ang1/2 ratio obviously dropped down in ALI group,compared to control groups(non severe cases of pneumonia and non-pulmonary disease).2) Serum elevated Ang-2 level in ALI patients indicates poor gas exchange, increased permeability of alveolar capillary membrane,and poor prognosis.3) Mechanical ventilation impose no significant influence on the serum level of Ang1,Ang2 in one week.