Study Of HMGB1 In Secondary Acute Lung Injury In Children With Severe Pneumonia

ObjectiveDespite the progress made in prevention and management,pneumonia remains the leading cause of death in children outside the neonatal period.Acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are serious complications of severe pneumonia.There is limited data to predict which children will experience negative outcomes,including clinical deterioration,severe illness or development of complications.A biomarker alone is not sufficient to predict clinical outcomes,and when biomarkers are used in combination with clinical variables,their predictive value is higher than that of any single biomarker or clinical parameter.However,up to now,no ideal biomarker has been found to predict acute lung injury.The ideal biomarker price should be relatively cheap,with little or no diurnal variation.The identification of new biomarkers for early diagnosis of acute lung injury and the development of more effective treatments are major research topics.Extracellular High mobility group box protein B1(HMGB1),which binds to specific receptors,leads to microvascular formation,enhances cell migration,promotes cell proliferation,and promotes inflammatory response,thereby aggravating inflammation and injury,and also plays an important role in ALI.The aim of this study was to analyze and investigate the levels of HMGB1 in serum and alveolar lavage fluid,so as to provide more evidence for the diagnosis and treatment of ALI.MethodsAccording to the "2019 Guidelines for the diagnosis and treatment of community-acquired pneumonia in children",eliminate congenital malformations,malignant tumor blood respiratory illness,hospital deaths in 24 hours,treated with immunosuppressant within six months before admission and Children with bronchoscopy contraindications,a total of 60 children with severe pneumonia,aged from 3 months to 14 years,admitted to the Pediatric Department of Qilu Hospital from November 2019 to January 2012 were selected.Serum samples were collected within 24 hours of admission,and samples of alveolar lavage fluid were collected from patients undergoing bronchoscopy and alveolar lavage during hospitalization.Enzyme linked immunosorbent assay(ELISA)was used to determine whether acute lung injury occurred 48 hours after admission.Serum levels of HMGB1 and IL-6 were measured 24 hours after admission and the levels of HMGB1 and IL-6 in alveolar lavage fluid in some children of the two groups were measured duration of hospital stay,and Clinical data of enrolled children,such as gender,age,clinical diagnosis,length of stay,CRP,PCT,LDH,D-DI,blood gas analysis were collected.SPSS26.0 and SAS9.4 statistical software were used to analyze and compare the differences in HMGB1,IL-6,CRP,PCT,WBC,N,PLT,LDH,D-DI between the two groups and the ability of predicting acute lung injury by various indicators in serum and alveolar lavage fluid.Therefore,the sensitive and specific indexes for the prediction of acute lung injury secondary to severe pneumonia were selected to provide the basis for the diagnosis and treatment of ALI.ResultsA total of 60 children with severe pneumonia meeting the diagnostic criteria were eventually included,including 30 children with ALI and 30 children without ALI.Serum specimens were collected in 31 cases,and ALI occurred in 14 children,while no ALI occurred in 17 children.Alveolar lavage fluid specimens were collected in 29 cases.ALI occurred in 16 cases and did not occur in 13 cases.There was no statistical difference in gender(P=0.114)and age(P=0.673)between the ALI group and the non-ALI group.(1)The mean concentration of HMGB1 in serum and alveolar lavage fluid were(33.57±10.28)ng/ml and(3.93±1.27)ng/m in ALI group.The mean concentrations of IL-6 in serum and alveolar lavage fluid were(36.66±14.97)pg/ml and(91.62±58.83)pg/ml,respectively.The mean concentrations of HMGB1 in serum and alveolar lavage fluid in the group without ALI were(6.48±3.94)ng/mL and(1.50±0.59)ng/m,respectively.The mean concentrations of IL-6 in serum and alveolar lavage fluid were(20.02±5.41)pg/ml and(12.44±11.88)pg/ml,respectively.(2)There was a significant positive correlation between serum HMGB1 and IL-6 concentration in the ALI group(r=0.629,P=0.016)and alveolar lavage fluid samples(r=0.814,P<0.05).There was no significant correlation between serum HMGB1 and IL-6 concentration in the non-ALI group(r=0.195,P=0.454).(3)The AUC values of HMGB1,IL-6,N,PCT,CRP,D-D1 and WBC in predicting the occurrence of ALI in severe pneumonia were 0.801,0.963,0.719,0.672,0.644,0.628 and 0.569,respectively.The predictive value of serum HMGB1 and other indicators for the occurrence of ALI in severe pneumonia was ranked as IL-6>HMGB1>N>PCT>CRP>D-DI>WBC.IL-6,HMGB1 and N played a significant role in predicting ALI,while PCT,CRP,D-DI and WBC played a weak role in predicting ALI.(4)Serum HMGB1 at admission can predict ALI 48h after admission in children with severe pneumonia.The best cutoff value of serum HMGB 1 for ALI prediction is 14.01ng/ml,and the specificity is 1 and sensitivity is 0.467.The optimal cut-off value of serum IL-6 for ALI prediction was 23.95(pg/ml),and the sensitivity and specificity were 0.967 and 0.867,respectively.Conclusion(1)The mean concentrations of HMGB 1 and IL-6 in serum and alveolar lavage fluid in children with severe pneumonia with acute lung injury were higher than those in the non-acute lung injury group.(2)There was a significant positive correlation between HMGB 1 and IL-6 concentration in serum and alveolar lavage fluid in the acute lung injury group with severe pneumonia.(3)The best cutoff value of serum HMGB1 for predicting the occurrence of acute lung injury 48 hours after admission was 14.01ng/ml.