| Objective:Interstitial pulmonary disease is a fatal disease with high morbidity,mortality and prognosis in recent years.Idiopathic pulmonary fibrosis(IPF)and connective tissue-associated interstitial lung disease(CTD-ILD)are two common types of ILD.The purpose of this study was to evaluate the prediction of prognosis with serum biomarkers(KL-6,CXCL13)and their continuous changes in patients with interstitial lung disease,and explore a non-invasive and non-radiation disease management method.Methods:Hospitalized patients with IPF and CTD-ILD were enrolled prospectively from September 2016 to June 2019 whose medical information of gender,age,smoking history,chronic disease,medicine treatment,distance of 6MWT,lung function,modified Medical Research Council(m MRC)dyspnoea scale.The levels of serum sputum glycosylated antigen-6(Krebs Von den Lungen-6,KL-6)and B lymphocyte chemotactic factor C-X-C motif chemokine 13(CXCL13)were detected by chemiluminescent enzyme immunoassay and enzyme-linked immunosorbent assay and the relationship with lung function.The receiver operating characteristic(ROC)curves of these parameters were conducted and the area under the curve(AUC)was calculated to analyze the sensitivity and specificity of various serum biomarkers and lung function.Results:1.Expression and continuous changes of biomarkers used to evaluate prognosis of IPF patients(1)A total of 63 patients with IPF enrolled in our study that 23 case in progressive situation and 40 patients is stable.Laboratory data of IPF patients were collected at admission(0),the 3rd(3)and the 6th month(6)separately.The baseline level of serum KL-6 in the ILD patients was no difference between the stable and progressive group.Baseline levels of the two biomarkers were not predictive for the prognosis in IPF patients.There was no difference in m MRC scores between the patients in the stable and progressive group(P>0.05).Serum levels of KL-6 and CXCL13 among those patients in the progressive group were significantly higher than those in the stable group during the first 6 months of follow-up(1410.74±522.26 vs.817.23±536.8U/ml,71.48±24.26 vs.44.95±29.9 pg/ml,P<0.05).There were significant differences between the two groups during the first 3 months of follow-up with the distance of 6MWT,levels of FVC% and DLCO% and serum level of KL-6.We also found the distance of 6MWT,levels of FVC% and DLCO% and serum levels of KL-6 and CXCL13 were different between the two cohorts(P all <0.05).It showed that the serum level of KL-6 in the 6th month(M6-KL-6)independently predicted the prognosis of IPF patients after logistic regression analysis(OR=1.003,95%CI: 1.001-1.004).Cut-off values of the serum levels of KL-6 and CXCL13 in the assessment of IPF prognosis at the 6th month of follow-up were 1421U/ml and 52.21pg/ml,respectively.The AUC of serum levels of KL-6 and CXCL13,6MWD,FVC% and DLCO% in evaluating prognosis of IPF were 0.802,0.771,0.756,0.823 and 0.715,respectively.The sensitivity and specificity of the largest AUC(0.886)combined with the five parameters were 95.5% and 65.5% respectively.(2)With following up the patients with IPF,it was found that serum level of ΔKL-6 in two groups was no difference between groups which couldn’t be the predictor of IPF patients as prognosis factor(P>0.05).Instead,the difference of serum level of ΔCXCL13 between stable and progressive group was shown statistically significant within the first 3 months(P<0.05).The serum levels of ΔCXCL13 and ΔKL-6 in the patients at the point of the 3rd and 6th month were respectively correlated negatively with Δ6MWD,ΔFVC%,and Δ DLCO %.(3)There were 20 patients with antifibrotic treatment among the IPF cohort.It was found that there was no difference in serum level of KL-6 between the antifibrotic and non-antifibrotic treatment group(P>0.05).Differences were found significant between the two groups at baseline data of FVC%,DLCO% and 3-months point of follow-up of DLCO% and CXCL13(P<0.05).(4)In the 20 patients with treatment of pirfenidone,the serum levels of KL-6 and CXCL13 within 6 months had a downward trend after treatment.There were no significant changes in the distance of 6MWT and levels of FVC%,DLCO%,KL-6 and CXCL13 after treatment(P>0.05).2.Expression of biomarkers and their continuous changes in CTD-ILD patients(1)There were 40 CTD-ILD patients with 17 case in the progressive group and 23 case in the stable group.The baseline levels of serum KL-6 and CXCL13,FVC%,m MRC,DLCO%,and 6MWD in the CTD-ILD patients were no significant difference between the two groups.It was found that the distance of 6MWT,DLCO% and KL-6 in the third month and 6MWD,DLCO%,FVC%,KL-6 and CXCL13 in the first six month were differences(P<0.05).Binary logistic regression and stepwise forward regression was used and we found that KL-6(OR=1.003,95%CI: 1.001-1.005)was independent predictive factor after logistic regression analysis.At the 6th month of follow-up,the cut-off values of serum levels of KL-6 and CXCL13 in predicting the poor prognosis of CTD-ILD were 884.5U/ml and 56.1pg/ml,respectively.(2)It was found in the CTD-ILD patients that the distance of Δ6MWT,levels of ΔDLCO%,ΔFVC%,and serum levels of ΔCXCL13 and ΔKL-6 in the 3rd month and in the 6th month were different during the following-up period(Pall <0.05).The serum levels of ΔCXCL13 and ΔKL-6 were correlated negatively with ΔFVC%,and ΔDLCO % respectively.Conclusions:Serum level of KL-6 is an independent predictor of prognosis in IPF and CTD-ILD patients.High levels of serum KL-6 and CXCL13 may indicate poor outcome.The cut-off values of serum levels of KL-6 and CXCL13 are different in the evaluation of prognosis in patients with different types of ILD.Sequential measurements of biomarkers could be recommended in disease surveillance and outcome assessment in clinical management. |
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