The Role Of Neutrophil Gelatinase-associated Lipocalin For In-hospital Prognosis In Pneumonia Patients

Section Ⅰ The role of neutrophil gelatinase-associated lipocalin in predicting in-hospital prognosis in patients with pneumonia.BackgroundNeutrophil gelatinase-associated lipocalin(NGAL)is one of the most effective biomarkers to reflect epithelial injury,and has been used in the assessment system of acute kidney injury in the past.However,we found that NGAL also increased significantly in patients with community-acquired pneumonia(CAP).ObjectiveThe purpose of this study was to explore whether NGAL can be used as an evaluative indicator of the severity of lung injury caused by CAP.MethodsImaging,blood gas,and other inflammatory biomarkers were collected from 152 CAP patients at admission and their admission NGAL levels were measured.The follow-up period was 30 days,with the patients reaching clinical stability as the primary clinical outcome.ResultsThe rising trend of plasma NGAL level is consistent with the degree of disease progression reflected by PSI.Plasma NGAL was significantly higher in patients who did not reach clinical stability within 30 days than in those who did(P<0.01).High NGAL levels(>152 ng/mL)were found to be a predictor of clinical stability using COX regression,with an HR of 0.386(95% CI: 0.262-0.569,P<0.001).NGAL could predict the clinical stability of CAP patients,with an AUC of 0.759(95% CI: 0.662-0.858,P<0.001)and a C-index of 0.741(95% CI: 0.670-0.812).We further found that the COX regression model combining NGAL and PSI score(AUC=0.897;Cindex=0.803)/ CURB-65 score(AUC=0.873;C-index=0.757)provided a more precise risk assessment than using PSI score(AUC=0.878;C-index=0.803)/ CURB-65 score(AUC=0.849;C-index=0.725)alone.ConclusionsNGAL could be an indicator to evaluate the progression of CAP,and incorporating NGAL into the scoring system can enhance the forecast performance of PSI and CURB-65 in clinical stability.Section Ⅱ Combining Neutrophil gelatinase-associated lipocalin and metabolomics to explore the change of illness in pneumonia patients ObjectiveIn the first part,we demonstrated that NGAL can identify the risk of adverse events during hospitalization in patients with pneumonia.However,we still do not know the role what NGAL plays in the pathogenesis of pneumonia.Metabolomics can simultaneously detect hundreds of metabolites in a short period of time through highthroughput technical means,and perform quantitative and qualitative analysis on them.Metabolomics can be used to study biological processes such as synthesis,degradation and regulation of metabolites in organisms,and to explore their relationship with biological functions and regulatory mechanisms.The purpose of this study is to explore the role of NGAL in the pathological process of pneumonia by analyzing the predictive effect of NGAL on pneumonia patients from the perspective of metabolomics.MethodsIn this study,94 patients with pneumonia and 27 healthy controls were included.Plasma NGAL levels were measured and untargeted metabolomics were analyzed by UHPLC-Q-TOF-MS.Pearson’s correlation analysis was used to explore the correlation between metabolites and NGAL and other clinical indicators.The variables were screened by Lasso algorithm,and the Cox regression model was constructed and compared with PSI and CURB-65 scores.ResultsThe level of plasma NGAL in patients with pneumonia was significantly higher than that in healthy controls,and it was related to the severity of the disease.There were significant disorders of 11 metabolites in patients with pneumonia,including Heptanoic acid,Pentadecadienoic acid,Hydroxyvaleric acid,Cholestenoic acid,Palmitic acid,Arachidonic acid,9,11-octadecadienoic acid,Docosapentaenoic acid,Alanylleucine,linolenic acid and 5,9,12-octadecatrienoic acid can distinguish patients with severe pneumonia from patients with mild pneumonia.Arachidonic acid and Docosapentaenoic acid were significantly correlated with clinical indexes such as NGAL,procalcitonin,lymphocytes and D-dimer,and were significantly correlated with clinical score PSI and CURB-65 score.NGAL,D-dimer,lymphocyte count,oxygenation index,arachidonic acid and Docosapentaenoic acid were used as variables to construct Cox regression model.The area under the curve(AUC)for predicting the severity of pneumonia,entering ICU and hospital death at 3 months were 0.97,0.93,0.96,respectively,which were significantly higher than the ability of PSI and CURB-65 scores to predict related events.ConclusionOur study found that the metabolomics method based on UHPLC-Q-TOF-MS can be successfully applied to identify the risk of exacerbation in patients with pneumonia at the time of admission,and found that fatty acids are closely related to NGAL,a novel lung injury marker.Our findings provide new insights and evidence for the role of NGAL in the pathological process of pneumonia.Combining NGAL with metabolomics can lead to better clinical management and risk stratification of patients.General conclusions of the studyThe level of NGAL at admission can be used to classify the risk and prognosis of pneumonia patients.Plasma NGAL level at admission can predict the severity of pneumonia and the possibility of reaching clinical stability,and can be used as an early monitoring indicator of pneumonia.We combined NGAL with PSI scores and CURB-65 scores to establish a COX regression model that outperformed CURB-65 and PSI scores in prognostic assessment.Our study found that the metabolomics method based on UHPLC-Q-TOF-MS can be successfully applied to identify the risk of exacerbation in patients with pneumonia at the time of admission,and found that fatty acids are closely related to NGAL,a novel lung injury marker.Our findings provide new insights and evidence for the role of NGAL in the pathological process of pneumonia.Combining NGAL with metabolomics can lead to better clinical management and risk stratification of patients.