Prediction Of Coronary Artery Dilatation In Children With Kawasaki Disease By Plasma Hydrogen Sulfide Concentration And Leukocyte Hydrogen Sulfide Production Rate

Objective:This study was designed to determine whether plasma hydrogen sulfide（H₂S）concentration and leukocyte H₂S production rates are potential biomarkers for predicting coronary artery dilatation（CAD）in children with Kawasaki disease（KD）.Method:A total of 37 children who were diagnosed as KD and hospitalized in the Children’s Hospital of Shaanxi Provincial People’s Hospital from Feb.2017 to Feb.2018 were enrolled as the KD group.These patients were divided into coronary artery dilatation group（CADs）and non-coronary artery dilatation group（NCADs）according to the follow-up results of echocardiography.46 children with other common febrile diseases who were hospitalized in the same period were collected as the ordinary fever group and33 children in outpatient health check-ups as the healthy control group.All the patients in the KD group were treated with 2g/kg/d high-dose intravenous immunoglobulin（IVIG）for one time and 30-50mg/kg/d oral aspirin.The dose of aspirin decreased to 3-5mg/kg/d after the body temperature returned to normal.2ml of peripheral venous blood was collected in the KD group and the ordinary fever group after diagnosis and before treatment as well as in the healthy control group.Plasma samples of 1ml venous blood were separated and measured their hydrogen sulfide（H₂S）concentration immediately.In addition,the remaining 1ml venous blood samples were pre-treated（including leukocyte separation,cell cleaning,cell count and cell cryopreservation）for detection of H₂S production rates in leukocytes.Levels of plasma H₂S were detected by sensitive sulfur electrode method.Lymphocyte hydrogen sulfide production rates were detected using the human H₂S enzyme linked immunosorbent assay（ELISA）kits.Relevant laboratory test indicators were collected from medical records.Result:1.A total of 116 children were enrolled in this study,including 37 cases in the KD group,46 cases in the ordinary fever group and 33 cases in the healthy control group.The H₂S production rate and WBC count in the KD group were significantly higher than those in the ordinary fever group and the healthy control group（P<0.05）,and the CRP level in the KD group was significantly higher than that in the other two groups（P<0.017）.RBC,HGB and HCT in the KD group were significantly lower than those in the ordinary fever group and the healthy control group（P<0.05）,and the plasma H₂S concentration was significantly lower than that in the other two groups（39.47±9.38 vs 66.59±22.24,39.47±9.38 vs 60.16±19.26,P<0.001）.Binary Logistic regression analysis showed that increased WBC,leukocyte H₂S production rate and decreased HGB,plasma H₂S concentration were independent risk factors for the onset of KD.2.There were 8 cases of CADs and 29 cases of NCADs.The incidence of CAD in the KD group was 21.62%.There was no significant difference between the incidence of CAD in this study and the known total CAD incidence in KD patients（about25%）（P>0.05）.There were no significant differences in the WBC,RBC,HGB,HCT,PLT,CRP levels and plasma H₂S concentration between CADs and NCADs（P>0.05）.The leukocyte H₂S production rates of CADs were significantly higher than that of NCADs（16.25±1.88 vs 12.30±1.88,P<0.001）.Binary Logistic regression analysis showed that the increased leukocyte H₂S production rate was an independent risk factor for CAD.Using ROC curve to analyze the H₂S production rate of leukocytes predicting the occurrence of CAD,the area under the curve was 0.940;When the H₂S production rate of leukocytes was more than 15.09 nmol/min/10⁸,the sensitivity and specificity for predicting the occurrence of CAD in children with KD were 87.5%and 96.6%respectively.3.There was no correlation between plasma H₂S concentration as well as leukocyte H₂S production rate and WBC,RBC,HGB,HCT,PLT before treatment in the KD group（P>0.05）.There was a positive correlation between leukocyte H₂S production rate and CRP（r=0.346,P=0.036）.Conclusion:Increased hydrogen sulfide production rate of leukocytes in children with Kawasaki disease in the acute age can be an effective predictor of coronary artery dilatation.When the H₂S production rate of leukocytes was more than 15.09 nmol/min/10⁸,the sensitivity and specificity for predicting the occurrence of CAD were 87.5%and 96.6%respectively.Reduced plasma hydrogen sulfide concentration is associated with the pathogenesis of Kawasaki disease.