Value Of Annexin A2 Combined With PSI Score In Predicting Severity And Prognosis Of Community-acquired Pneumonia In Adults

1.ObjectiveCommunity-acquired pneumonia(CAP)is a common disease in the respiratory department.In recent years,the number of patients worldwide who need intensive care treatment due to Severe community-acquired pneumonia(SCAP)is increasing.Disease severity assessment is an important component of the initial assessment of CAP patients,which is helpful for clinicians to make important diagnosis and treatment decisions.Currently,there is no definitive biomarker or scoring system that has been fully validated and widely implemented in clinical practice.Annexin A2(ANXA2)can play an important role in pathogen infection by participating in the fibrinolytic process,regulating the activation of inflammatory bodies,regulating inflammatory pathways and the release of inflammatory mediators.Previous studies have shown that the Pneumonia severity index(PSI)score has a high specificity in determining the severity of patients,whether or not to stay in an Intensive care unit(ICU),and in evaluating prognosis.Therefore,this study mainly discusses the predictive value of ANXA2 combined with PSI score in the severity and prognosis of adult patients with CAP.2.Research object and method2.1 Research objectAccording to 2018 Guideline for Primary Diagnosis and Treatment of Community-Acquired Pneumonia in Adults,a prospective study was conducted to select the patients diagnosed with CAP in the Department of Respiratory and critical Medicine from March 2022 to November 2022 in the second Hospital of Shandong University.According to the inclusion and exclusion criteria,a total of 176 patients with CAP were enrolled.Excluding patients with malignant tumors,new thrombotic diseases and incomplete medical records,162 patients with CAP were included.According to the diagnostic criteria,the patients were divided into non-severe group and severe group.40 patients with severe pneumonia and 122 patients with nonsevere pneumonia were collected,At the same time,48 patients were included in the physical examination center as the control group.According to the clinical outcome at 28 days,the severe pneumonia group was divided into survival group(n=24)and death group(n=16).2.2 Research methodThe abdominal peripheral blood samples were collected on the first day and the third day after admission,and the lavage fluid samples were collected by bronchoscopy or bronchoalveolar lavage within 3 days after admission,and the control group collected fasting peripheral blood samples.The levels of ANXA2 and interleukin-6(IL-6)in serum and lavage fluid samples collected from severe group,non-severe group and control group were measured by enzyme-linked immunosorbent assay(ELISA).The results of clinical data,laboratory index,etiology and imaging were collected by electronic medical record system.By comparing the expression levels of ANXA2 in serum and lavage fluid of patients with different severity of CAP,the correlations between them and different inflammatory biomarkers and pneumonia scores was evaluated by pairwise correlation analysis.in order to screen out sensitive and specific indicators for predicting the prognosis of pneumonia,The receiver operating characteristic(ROC)curve was used to evaluate the efficacy of individual and combined application of each index in predicting mortality in patients with SCAP.3.ResultsA total of 40 patients in the critical group,122 patients in the non-severe group and 48 patients in the control group were included.According to the 28-day clinical outcome,the severe group was divided into survival group(n=24)and death group(n=16).The main results were as follows:①The age of the severe group was 76(66,81)years old,which was significantly higher than that of the non-severe group 64(53,74)years old and the control group 56(52,71)years old(P<0.001),while there was no significant difference in the age between the non-severe group and the control group(P=0.132).There was no significant difference in sex,smoking history,drinking history,coronary heart disease,diabetes,hypertension,bronchial asthma and chronic obstructive pulmonary disease among the three groups(P>0.05).The proportion of severe group with hepatic and renal insufficiency and cerebrovascular history was significantly higher than that in non-severe group,and there was statistical difference between them(P<0.05).PCT,CRP,NEU,HCT,BUN,D-Di,CURB-65,PSI score,pleural effusion and multiple lobe infiltration in the severe group were higher than those in the non-severe group,and there was significant difference between the two groups(P<0.05),but there was no significant difference in LYM,FIB,PLT,Cr and blood Na+between the two groups(P>0.05).②The serum ANXA2 level in severe group on the day of admission was 25.52(15.26,43.84)ng/ml,which was significantly higher than that in the non-severe group and in the control group,with statistical significance(P<0.001).Further pairwise comparison revealed that the expression level of ANXA2 in the non-severe group was higher than that in the control group(P<0.001).The ANXA2 level in the severe group(n=40)was 28.70(13.25,69.92)ng/ml,higher than that in the nonsevere group(n=21),which was 15.37(7.19,29.03)ng/ml.There was a statistically significant difference between the two groups(P=0.034).③The serum IL-6 level collected on the first day after admission of the severe group was significantly higher than that of the non-severe group and the control group on the day of admission(P<0.001).④The pairwise analysis of serum ANXA2 and other indexes by Spearman correlation method showed that serum ANXA2 was significantly correlated with IL6,PCT,CRP,PSI score,CURB-65 score and lavage fluid ANXA2(P<0.05).⑤The differences of serum ANXA2 expression among different pathogen groups were compared.There was no significant difference in serum ANXA2 expression among different pathogens(bacteria,viruses,fungi,atypical pathogens,mixed infection,undetected group)(P=0.211).⑥The overall clinical characteristics of the survival group and the death group were analyzed,there were significant differences in PSI score,lavage fluid ANXA2,serum IL-6 and serum ANXA2 on the 3rd day after admission(P<0.05),but there was no significant difference in age,sex,history of smoking and drinking,complicated with basic disease history,serum ANXA2 collected on the first day after admission,PCT,CRP,WBC,NEU,PLT,Cr,BUN,D-Di,Na+,GLU,ALB,LYM and FIB(P<0.05).⑦Univariate analysis variables including lavage fluid ANXA2,ANXA2,IL-6 and PSI score on the 3rd day after admission were included in binary Logistic regression analysis.The results showed that lavage fluid ANXA2(OR1.023,95%CI 1.002-1.044)and PSI score(OR1.086,95%CI 1.010-1.168)were independent risk factors for in-hospital mortality of SCAP patients.⑧In order to judge whether ANXA2 concentration,PSI score and ANXA2+PSI score can be used to predict the death of patients with pneumonia,the ROC curve was established.The area under the curve was ANXA2(AUC=0.866,95%CI:0.7470.984,P<0.001),PSI score(AUC=0.816,95%CI:0.687-0.946,P<0.001),ANXA2+PSI score(AUC=0.878,95%CI:0.772-0.983,P<0.001).According to the concentration of ANXA2,the Cut-off value was 28.71ng/mL,and the corresponding sensitivity and specificity were 0.938 and 0.75 respectively.4.Conclusion①The serum ANXA2 level collected on the first day after admission in the severe pneumonia group was significantly higher than that in the non-severe pneumonia and in the control group.The results showed that the expression level of ANXA2 increased in the pneumonia group,and its expression level increased as the condition worsened.The results of correlation analysis showed that the serum ANXA2 concentration was positively correlated with IL-6,PCT,CRP,PSI score and CURB-65 score,suggesting that the level of ANXA2 was closely related to the severity of CAP.②The results of multivariate analysis showed that ANXA2 concentration in lavage fluid and PSI score were independent risk factors for predicting mortality in patients with CAP,suggesting that the clinical application of ANXA2 and PSI score in lavage fluid has certain reference significance in predicting the prognosis of severe community-acquired pneumonia.Compared with the application of PSI score and ANXA2 concentration in lavage fluid alone,the combination of them has higher sensitivity and specificity and has more clinical value.③The results showed that there was no significant difference in the expression of serum ANXA2 among different pathogens,suggesting that ANXA2 had no significant significance in distinguishing the types of pathogen infection.