Pro-Adrenomedullin, Soluble Triggering Receptor Expressed on Myeloid Cells1and Clinical Parameters to Diagnose and Predict Prognosis in Acute Exacerbations of COPD
|School||Huazhong University of Science and Technology|
|Course||Diseases of the Respiratory System|
|Keywords||chronic obstructive pulmonary disease adrenomedullin precursor(Pro-ADM) soluble triggering receptor expressed on myeloid-1(sTREM-1) prognosis biomarker|
Objective:(1)To investigate the changes of plasma Proadrenomedullin and soluble triggering receptor expressed on myeloid-1in different groups and different periods of chronic obstructive pulmonary disease (COPD) and their clinical significance;(2)To evaluate the values of biomarkers and clinical parameters to predict the prognosis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Methods:Subjects are divided into three groups:AECOPD group(n=79), stable COPD (SCOPD) group (n=29), and healthy control (n=20)group. We collected the peripheral venous blood samples from these three groups respectively.In the AECOPD group, we selected17patients and collected their peripheral venous blood samples on14to30days and6months after their admission additionally. The plasma concentrations of Pro-ADM and sTREM-1of the three groups of subjects and three different periods of the17patients of AECOPD group were measured by enzyme-linked immunosorbent assay(ELISA). In addition to plasma Pro-ADM and sTREM-1, we evaluated the predictive value of clinical, laboratory, and functional parameters on half-year survival with Logistic regression univariate and multivariate analyses.We analyzed the time to clinical failure by Kaplan-Meier curves.Results:(1) Compared to healthy control group, the levels of plasma Pro-ADM were significantly increased on AECOPD group and SCOPD group,(P<0.001and P<0.001, respectively), but the levels on AECOPD group and SCOPD group were similar(P=0.217); Plasma levels of sTREM-1were similar among AECOPD group, SCOPD group and healthy control group (P=0.065); Plasma Pro-ADM and sTREM-1of17patients of AECOPD group were detected in acute phase, remission, and stable phase, and the concentrations of Pro-ADM were (559.41±33.20) pg/ml,(456.47±32.84) pg/ml, and (216.47±24.72) pg/ml respectively, and the variance among the three stages had statistical significance (P<0.001); Plasma concentrations of sTREM-1were (15.36±1.82) pg/ml,(9.87±1.19) pg/ml, and (8.36±1.04) pg/ml respectively, the difference was statistically significant (P<0.001).(2) With the cut-off value of345pg/ml, Pro-ADM had a sensitivity of62.1%, specificity of90%respectively to diagnose SCOPD(P<0.001); The optimal threshold to identify patients of COPD(AECOPD and SCOPD) and health control was185pg/ml, the sensitivity and specificity were72.2%and65%(P<0.001).(3) Using multivariate analysis, the independent factors affecting the half-year survival rate are PaCO2(P=0.008, RR=1.197), CRP(P=0.017, RR=1.102) and WBC(P=0.028, RR=0.387) in the acute phase.(4) Kaplan-Meier survival curves shows, compared to the patients whose plasma levels of Pro-ADM were below375pg/ml, patients whose plasma levels of Pro-ADM>375pg/ml on hospital admission increased the risk of poor prognosis, the difference was statistically significant (P=0.03).Conclusions:Continuous observation of plasma levels of Pro-ADM and sTREM-1had some clinical values on reflecting the severity of AECOPD, plasma Pro-ADM can not only be used as a sensitive biomarker to identify COPD patients from healthy individuals, the levels on admission can partly predict prognosis of AECOPD. Plasma levels of Pro-ADM>375pg/ml on hospital admission increased the probability of occurring poor prognosis within six months from11.1%to44.1%(P=0.049). The independent factors affecting half-year survival rate are the levels of PaCO2, CRP and WBC in acute phase.