Study On The Correlation Between Bilirubin Level And Acute Exacerbation And Prognosis Of Idiopathic Pulmonary Fibrosis

Background:Idiopathic pulmonary fibrosis（IPF）is a chronic and progressive interstitial lung disease of unknown etiology,which usually occurs in middle-aged and elderly people.The prognosis of this disease is very poor,and the overall mean survival time is 3-5 years.At present,the pathogenesis of this disease is not clear,the treatment effect is poor,and the fatality rate is high.It has become one of the difficult diseases of the respiratory system.Oxidative stress is one of the main pathogenic way of IPF,studies have confirmed that the bilirubin of oxidative stress related lung disease has certain protective effect,convenient and bilirubin in clinic for economy,Therefore,this study aimed to compare the expression levels of bilirubin in patients with idiopathic pulmonary fibrosis between the stable stage and the acute exacerbation stage,and to evaluate the risk of acute exacerbation and the value of survival prognosis.Materials and methods:Retrospectively collected in January 2012-January 2018 in the first affiliated hospital of nanchang university of respiratory medicine in hospital,90 cases of IPF patients,according to the clinical types are divided into two groups:acute exacerbation period（AE-IPF period）,34 cases,stabilization 56 cases.The inclusion criteria for IPF and AEIPF were based on ATS/ERS in 2018 and the diagnostic criteria for idiopathic pulmonary fibrosis issued by Chinese Society of Respiratory Medicine.A total of 47 healthy people were collected from our hospital.Read the case of the object of study after admission documents,collection of age,sex,smoking history,admission time,the basic information such as phone number and make detailed records,collect laboratory related indicators,white blood cells（WBC）,hemoglobin（Hb）and platelets（PLT）,total bilirubin（TBIL）and indirect bilirubin（IBIL）,direct bilirubin（DBIL）,albumin（propagated）,lactate dehydrogenase（LDH）,creatine kinase（CK）and other relevant data,blood gas analysis:oxygen partial pressure（Pa O₂）,（Pa CO₂）,CO₂partial pressure of oxygen and index（P/F）;Lung function:total lung volume（TLC）,forced expiratory volume in the first second（FEV1）,forced vital capacity（FVC）,carbon monoxide dispersion（DLCO）,etc.Comparative analysis:1.Comparison of general and clinical data between the IPF group and the healthy control group.2.To analyze and evaluate the relationship between serum bilirubin level and pulmonary function indexes.3.Compare whether the serum bilirubin level is different between the AE-IPF and IPF stable phase groups.4.ROC curve was used to evaluate the predictive value of serum bilirubin in the acute exacerbation of IPF.5.The survival status of patients was recorded through follow-up,and ROC curve analysis was used to find the best cutoff value of serum bilirubin for predicting the prognosis of IPF.The predictive value of serum bilirubin for predicting the prognosis of IPF was analyzed by drawing the survival curve.6.Cox proportional risk regression model was used to analyze whether serum bilirubin was a prognostic factor for IPF.Result:1.There were statistically significant differences in TBIL,DBIL and IBIL between the IPF group and the control group（P<0.05）,and the levels of TBIL,DBIL and IBIL in IPF group were significantly lower than those in control group.2.The difference in TBIL and IBIL between AEIPF group and IPF stable group was statistically significant（P<0.05）,and the TBIL and IBIL levels of AEIPF were significantly lower than those of IPF stable period,while the difference in DBIL between the two groups was not statistically significant（P>0.05）.3.There was a positive correlation between TBIL and IBIL and DLCO%（r=0.380 and 0.449,respectively,both P<0.05）,and there was a positive correlation between IBIL and FVC%（r=0.073,P<0.05）.There was no statistical difference between DBIL and DLCO%,FVC%and TLC%（P>0.05）.4.Logisitic regression analysis showed that TBIL,IBIL,DLCO%,FVC%and smoking were independent risk factors for AE-IPF.5.The predictive value of bilirubin on acute exacerbation of IPF was evaluated by drawing ROC curve:the area under the curve of Ibil was 0.795（P<0.001）,and the optimal critical value is 5.2umol/L.The area under the curve of TBIL was 0.787（P<0.001）,and the cut value was 7.15umol/L;The predictive value of bilirubin for survival prognosis of IPF was evaluated by drawing ROC curve:the area under the curve of TBILwas 0.783（P<0.001）,the optimal critical value 8.2umol/L.The area under the curve of IBIL was 0.779（P<0.001）,the optimal critical value is 5.35umol/L.Log Rank test showed that TBIL and IBIL medium high group（TBIL>8.2 umol/L,IBIL>5.35umol/L）had higher survival rate than low group（TBIL≤8.2 umol/L,IBIL≤5.35 umol/L）.6.Cox univariate proportional risk regression analysis showed that age,smoking,PO₂,PCO₂,P/F,DLCO%,TLC%,FVC%,albumin,CK,TBIL,IBIL,DBIL were associated with the prognosis of IPF（P<0.05）.Cox multivariate proportional risk regression analysis showed that age,smoking,DLCO%,TBIL and IBIL were independent prognostic factors for the prognosis of IPF（P<0.05）.Conclusions:1.The levels of TBIL,IBIL in patients with IPF are lower than those in healthy people,and with the acute aggravation of IPF and the decrease of lung function,the levels of TBIL and IBIL gradually decrease.2.The levels of TBIL and IBIL can predict the risk of acute exacerbation in patients with IPF.When TBIL≤7.15umol/L or IBIL≤5.2umol/L,the risk of acute exacerbation of IPF increases.3.TBIL and IBIL are independent risk factors for the prognosis of IPF.When TBIL≤8.2umol/L or IBIL≤5.35umol/L,the risk of poor prognosis of IPF is increased.