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
• α 2 macroglobulin
• matrix metalloproteinase-9

Statement of Ethics

Changzhou Second Hospital granted Ethical approval to carry out the study within its facilities ([2022]KY113-01). This study was designed, implemented, and reported in accordance with the ethical principles laid down in the Declaration of Helsinki.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by grants from the Jiangsu province social development project (BE2020651 to Q.Z.), and in part from the Jiangsu province “333 talents” project (BRA2020015 to Q.Z.), the Changzhou Sci & Tech Program (CE20205023 to Q.Z.), and the Changzhou High-Level Medical Talents Training Project (2022CZLJ013 to Q.Z.).