Clinical Significance Of Blood Inflammatory Markers In Pulmonary Hypertension Associated With Interstitial Lung Disease

Objective To investigate the clinical significance of blood inflammatory markers such as neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR)and systemic immune-inflammation index(SII)in ILD-PH.Methods Retrospective analysis was performed on the ILD patients in The First Affiliated Hospital Of USTC from June 2017 to April 2022,and the patients were divided into ILD-PH group and non-PH group according to whether the patients had secondary PH.We also set up a healthy control group.Blood inflammatory markers such as NLR,PLR,MLR and SII were calculated according to blood routine.These indexes were compared among the three groups,and the predictive value of ILD and PH was evaluated by drawing receiver operating characteristic(ROC)curve.In addition some indicators of ILD patients were collected such as basic clinical medical records(including: Gender,age,smoking and drinking history,course of disease,height,weight,body mass index(BMI),length of stay in hospital,whether to use hormone,etc.),blood routine indexes,biochemical indexes,lactate dehydrogenase,erythrocyte sedimentation rate,C-reactive protein(CRP),procalcitonin,coagulation function indexes,N-terminal pro-Brain-type natriuretic peptide(NT-pro BNP),blood gas analysis indexes,lung function indexes,etc.The differences between ILD and non-PH groups were compared to further explore the independent risk factors for PH in ILD patients.In addition,correlation analysis was conducted to explore the correlation between NLR,PLR,MLR and SII with other factors.SPSS26.0 software was used for statistical analysis.Normal distribution data were expressed as (?)±s,and differences between groups were tested by single factor ANOVA(statistic F).The non-normal distribution data were described by the interquartile spacing,and the differences between groups were tested by the non-parametric Kruskal-Wallis test H(statistic H),the significance values were adjusted by Bonferroni correction method.The diagnostic value was evaluated according to the area under curve(AUC),and the appropriate cut-off value of the best combination of sensitivity and specificity was determined by the Youden index.Multivariate binomial logistic regression analysis was used to find risk factors for pulmonary hypertension.Spearman rank correlation analysis was used for data that did not meet bivariate normal distribution or rank distribution.P< 0.05 was statistically significant.Results 1.A total of 79 cases in non-PH group,72 cases in ILD-PH group and 167 cases in healthy control group were collected.The results showed that there were significant differences in NLR,PLR and SII among the three groups(ILD-PH group >non-PH group > healthy control group).For predicting ILD,the AUC of NLR was0.723(0.654,0.793),the optimal cut-off value was 2.33,the sensitivity was 43%,and the specificity was 93%.The AUC of MLR was 0.726(0.653,0.799),the optimal cut-off value was 0.25,the sensitivity was 68%,and the specificity was 72%.The AUC of SII was 0.757(0.689,0.825),the optimal cut-off value was 471.16,the sensitivity was 56%,and the specificity was 86%.2.CRP,direct bilirubin,prothrombin time(PT),international normalized ratio(INR),D-dimer and NT-pro BNP in ILD-PH group were higher than those in non-PH group,while albumin,forced vital capacity(FVC),FVC%,forced expiratory volume in the first second(FEV1),FEV1%,vital capacity(VC)%,total lung capacity(TLC)%,residual volume(RV)% and oxygenation index(OI)in ILD-PH group were lower than those in non-PH group.For predicting secondary PH in ILD patients,the AUC of NLR was0.749(0.670,0.827),the optimal cut-off value was 3.25,the sensitivity was 61%,and the specificity was 80%.The AUC of SII was 0.726(0.644,0.807),the optimal cut-off value was 574.97,the sensitivity was 78%,and the specificity was 66%.The AUC of NT-pro BNP was 0.731(0.602,0.860),the optimal cut-off value was 290.5,the sensitivity was 58%,and the specificity was 82%.By combining NLR,PLR,MLR,SII with CRP,direct bilirubin,PT,INR,D dimer and NT-pro BNP to predict the PH of ILD patients,the area under ROC curve(AUC)was 0.872(0.770,0.973),the sensitivity was 85%,and the specificity was 82%.3.Correlation coefficients of NLR,SII with CRP were 0.559,0.570;The correlation coefficients of NLR,MLR,SII with PASP were 0.480,0.340,0.395.The correlation coefficients of NLR,MLR,SII with length of hospitalization were 0.274,0.254,0.252.The correlation coefficients of NLR,MLR,SII and hormone use were 0.240,0.199,0.249.Conclusions 1.When NLR,MLR and SII increase,it has certain predictive value for ILD occurrence.2.When NLR,SII and NT-pro BNP increase,it has certain predictive value for PH occurrence in ILD patients.The combined prediction value and accuracy of NLR,PLR,MLR,SII,CRP,direct bilirubin,PT,INR,D-dimer and NT-pro BNP in the diagnosis of PH in ILD patients was significantly improved compared with the single index.3.NLR,SII were significantly positively correlated with CRP,and NLR,MLR and SII were positively correlated with pulmonary arterial systolic pressure(PASP),an important indicator for the diagnosis of PH.The higher the NLR,MLR and SII,the longer the hospital stay,and the greater the probability of hormone use,whith may indicate the severity of the disease and poor prognosis.