Severity of chronic obstructive pulmonary disease with 'exacerbator with emphysema phenotype' is associated with potential biomarkers

Abstract

Objective: The present study was designed to investigate the biomarkers levels of fractalkine (FKN), neutrophil elastase (NE) and matrix metalloproteinase-12 (MMP-12) in chronic obstructive pulmonary disease (COPD) with 'exacerbator with emphysema phenotype' and to evaluate the associations between the biomarkers levels and the severity of disease by spirometric measurements.

Methods: A total of 84 COPD patients and 49 healthy controls were enrolled in our study. ELISA were utilised to detect the FKN, MMP-12 and NE in serum from all subjects.

Results: FKN (p<0.001), NE (p=0.039) and MMP-12 (p<0.001) in serum of COPD patients showed higher levels than that of healthy control subjects. Serum FKN (p<0.001), MMP-12 (p<0.001) and NE (p=0.043) levels were significantly higher in severe and very severe COPD patients than that in mild and moderate COPD patients. Circulating FKN, MMP-12 and NE expression levels were significantly elevated (p<0.001) in COPD smokers compared with COPD non-smokers. The smoke pack years were negatively correlated with FEV₁%pred (r=-0.5036), FEV₁/FVC ratio (r=-0.2847) (FEV, forced expiratory volume; FVC, forced vital capacity). Similarly, we observed a strong positive correlation between the smoke pack years and serum levels of FKN (r=0.4971), MMP-12 (r=0.4315) and NE (r=0.2754). FEV₁%pred was strongly negatively correlated with cytokine levels of FKN (r=-0.4367), MMP-12 (r=-0.3295) and NE (r=-0.2684). Likewise, FEV₁/FVC ratio was negatively correlated with mediators of inflammation levels of FKN (r=-0.3867), MMP-12 (r=-0.2941) and NE (r=-0.2153).

Conclusion: Serum FKN, MMP-12 and NE concentrations in COPD patients are directly associated with the severity of COPD with 'exacerbator with emphysema phenotype'. This finding suggests that FKN, MMP-12 and NE might play an important role in the pathophysiology of COPD.

Keywords: FKN; chronic obstructive pulmonary disease; exacerbator with emphysema phenotype; matrix metalloproteinase-12; neutrophil elastase.