Biomarkers For Early Prediction Of Sepsis-induced Acute Respiratory Distress Syndrome And Prognostic Significance Of Th17/Treg Balance

Objectives 1.We sought to investigate the performance of Surfactant Protein D（SP-D）,interleukin-8（IL-8）,interleukin-6（IL-6）,amino-terminal brain natriuretic peptide(NT-BNP,D-dimmer,von Willebrand factor（vWF）,platelet（PLT）in early prediction of ARDS induced by sepsis.2.Moreover,we sought to investigate the feasibility of Th17/Treg ratio and related interleukin-17（IL-17）to predict the prognosis of ARDS induced by sepsis.Methods 1.We investigated 218 sepsis patients admitted in the ICU of the second hospital of Tianjin Medical University.Forty-eight patients with sepsis-related ARDS and forty patients with sepsis,which had been matched in sex and age,were prospectively studied.The levels of SP-D,IL-8,IL-6,NT-BNP,D-dimmer,PLT and the activity of vWF were quantitatively measured within 24 hours after the diagnosis of sepsis.The risk prediction model of ARDS induced by sepsis was constructed by using 7 biomarkers as independent variables and with or without ARDS before discharge from hospital as dependent variables.All biomarkers with predictive value were screened by binary logistic regression analysis.2.40 patients with ARDS induced by sepsis were enrolled in the further study.Blood samples were collected within 24 hours after the diagnosis of ARDS.CD4 + lymphocyte subsets of Th17 percentage and Treg percentage were detected by flow cytometry,and Th17/Treg ratio were calculated subsequently;Serum concentrations of IL-17,C-reactive protein（CPR）and procalcitonin（PCT）were measured.Forty patients with ARDS were followed up and divided into survival group and non-survival group according to the clinical outcome in 28 days.The baseline characteristics and the levels of CD4 + lymphocyte subsets and related inflammatory biomarkers of subjects were detailed in table.The ROC curves of the 28-day death probability of sepsis-related ARDS were constructed and the cutoff values of Th17 / Treg ratio were calculated based on Yuden index（YI）,the sensitivity,specificity and the values of positive predictive and negative predictive were calculated subsequently.To investigate the performance of biomarkers for prognosis prediction of sepsis-related ARDS,a predictive model with independent variables of Th17 / Treg ratio,Pa O₂ / Fi O₂,IL-17,CRP,PCT and APACHE II score and two dependent variables of survival or non-survival within 28 days after diagnosis was constructed,followed by binary Logistic regression to select the biological index with predicted value for the prognosis of sepsis-related ARDS.Results 1.The area under the ROC curve（AUC）of SP-D,vWF and IL-8 for predicting ARDS was 0.758（P<0.01）,0.783（P<0.01）,0.747（P<0.01）respectively,and raised to 0.847（P<0.001）when the three combined.The cutoff value was 68.5μg/L,203.25%,62.5pg/m L respectively.The sensitivity was 0.667,0.646,0.771,0.729,the specificity was 0.775,0.850,0.625,0.775 respectively,positive predictive values were 0.781,0.838,0.711,0.75;negative predictive values were 0.66,0.667,0.694,0.700.2.The study of survivals and non-survivals of ARDS showed that the AUC of Th17 / Treg ratio,Th17 percentage,IL-17,APACHE II score and Th17 / Treg ratio combined with APACHE II score were 0.831,0.788 0.661,0.829 and 0.905,respectively.The sensitivity,specificity,positive predictive value and negative predictive value of Th17 /Treg ratio were 0.882,0.793,0.647 and 0.739,respectively.The Spearman correlation coefficients of the Th17 / Treg ratio and APACHE II score and PaO₂ / FiO₂ were 0.680（P<0.001）and-0.362（P=0.022）,respectively.The logistic regression of the ARDS prognosis prediction model showed that the APACHE II score and the Th17 / Treg ratio had a predictive value for the prognosis of sepsis-related ARDS,with odds ratios（OR）of 2.003（P=0.022）and 10.486（P=0.039）,respectively.Conclusion 1.SP-D,vWF and IL-8 could be used for the early prediction of sepsis-related ARDS,and the combination of the three biomarkers can improve the prediction accuracy and facilitate the early diagnosis of sepsis-related ARDS.2.Th17/Treg ratio is a potential biomarker for the risk stratification and the prognosis evaluation of sepsis-related ARDS.3.The comprehensive evaluation of Th17/Treg ratio,APACHE II score and PaO₂ / FiO₂ is recommended in clinical practice.