Objective:Adult Community acquired pneumonia(CAP),especially severe community acquired pneumonia,has caused a huge public health burden in terms of morbidity and mortality.Current infection-related biomarkers and pneumonia scoring systems have some limitations in evaluating the disease of CAP.Therefore,the search for a new factor with high specificity and sensitivity that can predict the severity of pneumonia in the early stage of infection has been the focus of research in the past two years.Histone H3 lysine 18 lactylation(H3K181a)promoted the polarization of M1-type macrophages to M2-type macrophages,and was involved in the pathologic and physiological processes of sepsis and immune regulation.The purpose of this study was to investigate the predictive value of H3K181a for the severity and prognosis of patients with CAP.Methods:1.A prospective study was conducted to screen 265 CAP patients admitted to the ward of the Department of Respiratory and Critical Care Medicine,the Second Hospital of Shandong University from November 2021 to November 2022.According to the inclusion and exclusion criteria of this study,108 patients who did not meet the criteria and 59 patients with incomplete data and missing patients were excluded.Ninety-eight patients with CAP were eventually included in the study.The healthy control group included 45 healthy adults from the physical examination Center of the Second Hospital of Shandong University.The gender and age of the healthy control group and the CAP group were matched.According to the 2018 edition of"Guidelines for Primary Diagnosis and Treatment of Adult Community-Acquired Pneumonia",patients in the CAP group were divided into 47 cases in the severe pneumonia group and 51 cases in the non-severe pneumonia group.According to the clinical outcome within 28 days after admission,the patients in severe pneumonia group were divided into survival group(40 cases)and death group(7 cases).2.The following clinical data were collected in the CAP group:age,sex,smoking and drinking history,comorbidities,pulmonary imaging changes,laboratory examination,pathogenic microbiology examination,complications and prognosis.The following data were collected from the healthy control group:age,sex,smoking and drinking history,etc.3.Peripheral blood 3ml of patients in CAP group was collected within 24 hours after admission,and 3ml of peripheral blood of healthy patients in fasting state in the morning on the day of physical examination was collected,and the following experimental operations were performed:(1)The expression level of H3K18la in Peripheral blood mononuclear cell(PBMC)was determined by Western Blot(WB).(2)The mRNA expression level of M2-type macrophage associated gene Arginase-1(Argl)in PBMC was determined by real-time quantitative PCR.(3)Serum Interleukin-6(IL-6)levels in peripheral blood were measured by enzyme-linked immunosorbent assay(ELISA).Results:1.There were no significant differences in age,sex,smoking history and drinking history between CAP group and healthy control group(P>0.05).The patients in CAP group were divided into severe pneumonia group(47 cases)and non-severe pneumonia group(51 cases),and the clinical data were compared between groups.Compared with the non-severe pneumonia group,patients in the severe pneumonia group had more underlying diseases and higher expression of infection-related biomarkers,such as Procalcitonin(PCT),IL-6,Neutrophil-tolymphocyte ratio,NLR,Lymphocyte(LYM)count was lower.The characteristics of lung imaging data were more pulmonary lobe infiltration,more likely to appear pleural effusion,and the pathogens detected were mainly bacteria.2.Among all the included groups,the expression level of H3K18la was the highest in patients with severe pneumonia,with the expression levels of 1.02±0.27 in patients with severe pneumonia,0.74±0.16 in patients with non-severe pneumonia and 0.46±0.16 in healthy control group,respectively.There was statistical difference among the three groups(P<0.0001).3.Receiver Operator Characteristic(ROC)Curve was used to determine the predictive level of H3K181a for severe pneumonia.The Area Under the Curve(AUC)was 0.813.P<0.0001,indicating that H3K18la is significant for the diagnosis of severe pneumonia.When the cutoff value of H3K18la was 0.85,the specificity and sensitivity of the diagnosis of severe pneumonia were 78.4%and 78.7%,suggesting that the H3K181a level above 0.85 was more favorable for the diagnosis of severe pneumonia.4.The correlations between H3K181a levels and White blood cell(WBC),Neutrophil(NEU),LYM,NLR,PCT,C-reactive protein(CRP)and IL-6 were analyzed.H3K181a levels were negatively correlated with LYM(r=-0.391,P<0.001),WBC(r=0.310,P<0.001),NEU(r=0.331,P<0.001),NLR(r=0.465,P<0.001),PCT(r=0.315,P<0.01),IL-6(r=0.784,P<0.001)were positively correlated,but not closely correlated with CRP(r=0.037,P=0.763).5.The correlation between H3K181a level and the score of pneumonia severity was analyzed.It was found that H3K181a level was correlated with Acute physiology and chronic health evaluationⅡ,APACHEⅡ)(r=0.5405,P<0.0001),PSI score of Pneumonia severity index(r=0.3868,P<0.001)and CURB-65 score(r=0.4429,P<0.001)were positively correlated.6.The correlation analysis between H3K181a level and Argl mRNA expression showed that H3K181a level was positively correlated with Argl mRNA expression level(r=0.416,P=0.025).7.According to the clinical outcome within 28 days after admission,patients in the severe pneumonia group were divided into survival group and death group.The results showed that the in-hospital fatality rate of patients with severe pneumonia was 14.9%,the death rate was mostly male(85.71%),and the patients were more likely to be complicated with pleural effusion(85.71%).Compared with the survival group,the expression level of H3K181a,CRP,PSI score and CURB-65 score in the death group were significantly higher than those in the survival group,with statistical significance(P<0.05).8.Variables with P<0.05 in univariate statistical analysis were included in binary Logistic regression analysis,and the results showed that:H3K181a(OR 33.003,95%CI 1.497-727.631,P=0.027),CURB-65(OR 6.671,95%CI 1.405-31.680,P=0.0.17)were independent risk factors for death in severe CAP patients.9.In order to determine whether H3K181a,CURB-65 score and H3K181a combined CURB-65 score can predict death of patients with severe pneumonia can be applied clinically,ROC curve was established,and the AUCs were calculated as follows:H3K181a(AUC=0.861,95%CI 0.84-1.00,P=0.003),CURB-65 scores(AUC=0.802,95%CI 0.658-0.945,P=0.012),H3K181a combined with CURB-65 score(AUC=0.923,95%CI 0.84-1.00,P<0.0001).The results showed that H3K181a combined with CURB-65 score had a higher predictive value for death in severe pneumonia patients compared with H3K181a or CURB-65 score alone.Conclusion:1.Compared with the non-severe pneumonia group and the survival group,the expression of H3K181a in the severe pneumonia group and the death group was higher within 24h after admission.Correlation analysis showed that H3K181a level was positively correlated with WBC,NEU,NLR,PCT,IL-6 and other infection-related biomarkers,as well as PSI score,CURB-65 score,and APACHE Ⅱ score,suggesting that H3K181a level could be a closely related factor indicating the severity and prognosis of CAP.2.H3K18la and CURB-65 scores can be used as independent risk factors to measure mortality in patients with severe pneumonia.Compared with CURB-65 score alone or H3K181a expression level alone,H3K181a combined with CURB-65 score could better predict the risk of death in patients with severe pneumonia. |