A2M Serves as Promising Biomarker for Chronic Obstructive Pulmonary Disease

Abstract

Background: Chronic obstructive pulmonary disease (COPD) often associated with cigarette smoking. However, increasing evidence suggests that non-smoking COPD is much higher than previously thought. This study aims to identify a nonsmoking COPD biomarker and examined its value in diagnosis and prediction of acute exacerbation.

Methods: A total of 35 stable COPD patients, 70 acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients and 35 healthy control subjects were included. Plasma α 2 macroglobulin (A2M) and matrix metalloproteinase-9 (MMP-9) levels were measured using the enzyme-linked immunosorbent assay (ELISA) method on all participants. Their association with clinical characteristics and lung function parameters were determined by regression analysis. Receiver operating characteristic (ROC) curve was used to determine the diagnostic sensitivity and specificity. Correlation coefficients were evaluated using Pearson's correlation.

Results: Plasma A2M concentration was decreased and MMP-9 concentration, MMP-9/A2M ratio were elevated in stable COPD patients compared with control groups. And MMP-9 expression was significantly higher in AECOPD patients. A2M level was increased in AECOPD patients with infection compared with those without. In addition, there was no statistical difference in A2M levels between smokers and nonsmokers COPD or healthy control subjects. Furthermore, A2M, MMP-9 and MMP-9/A2M were correlated with forced expiratory volume in one second (FEV₁)%, FEV₁/ forced vital capacity (FVC), CAT and mMRC score in COPD patients, but had no correlation with fraction of exhaled nitric oxide (FeNO) and concentration of alveolar nitric oxide (CaNO).

Conclusion: A2M is altered in peripheral blood of COPD patients and correlated with severity and infection. Moreover, there was no significant correlation between the change in A2M and smoking, FeNO and CaNO, suggesting A2M may reflect the overall rather than local inflammation in COPD patients and serve as a potential biomarker for nonsmoking COPD patients.

Keywords: chronic obstructive pulmonary disease; matrix metalloproteinase-9; α 2 macroglobulin.

Figure 1

(A and B) Expression levels of A2M and MMP-9 in plasma between stable COPD patients and healthy group by ELISA were measurement. (C) Pearson’s correlation analysis was employed to reveal the relationship between A2M and MMP9. (D) MMP-9/A2M ratio in stable COPD patients compared with the control groups. Differences between the groups were assessed by two-sample independent Student’s t-test analysis. ****P < 0.0001.

Figure 2

(A and B) Expression levels of A2M and MMP-9 between healthy nonsmoking group, healthy smoking group, COPD nonsmoking group and COPD smoking group. Differences between the groups were assessed by one-way analysis of variance. NS: no significant (P > 0.05), *P < 0.05.

Figure 3

(A and B) Performances of A2M and MMP-9/A2M in the diagnosis of COPD.

Figure 4

(A) Expression levels of MMP-9 between stable COPD group and AECOPD group. (B) Value of MMP-9 in predicting acute exacerbation of COPD. (C) Based on two-sample independent Student’s t-test analysis, expression levels of A2M between stable COPD group and AECOPD group. Differences between the groups were assessed by two-sample independent Student’s t-test analysis. NS: no significant (P > 0.05), ****P < 0.0001.

Figure 5

Expression levels of A2M between non-infection AECOPD group and infection AECOPD group. Differences between the groups were assessed by two-sample independent Student’s t-test analysis. ****P < 0.0001.