Background: Matrix metalloproteinase-12 (MMP-12) and Tissue inhibitor of metalloproteinase-4 (TIMP-4) play important roles in the pathophysiology of chronic obstructive pulmonary disease (COPD). Subjects of many previous studies were patients with severe and very severe COPD. However, there are comparatively few studies on patients with mild-to-moderate COPD. Our aim was to measure MMP-12 and TIMP-4 levels and to compare its levels in various materials in patients with mild-to-moderate acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We also compared which of the two materials of these biomarkers was better correlated with disease severity and DODE index.
Methods: A total of 39 patients with AECOPD and 25 control subjects were enrolled in our study. MMP-12 and TIMP-4 in different respiratory samples were detected by ELISA.
Results: Expression levels of MMP-12 in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) and TIMP-4 in BALF were significantly higher in AECOPD patients than that in healthy subjects (P < 0.001). However, there was no significant difference in TIMP-4 level in EBC of AECOPD patients compared to healthy subjects (P = 0.0527). The levels of MMP-12 in BALF and EBC and TIMP-4 in BAFL of AECOPD patients were significantly correlated with FEV1% predicted (P < 0.001). However, in AECOPD patients, there was no significant correlation between TIMP-4 levels in EBC and BODE index (r = 0.4175, P = 0.0559).
Conclusion: During mild-to-moderate AECOPD, the levels of MMP-12 and TIMP-4 in BALF were better correlated with FEV1% predicted and BODE index than that in EBC, indicating that they may be new target interventions for pharmacology to prevent and/or treat AECOPD.
Keywords: Bronchoalveolar lavage fluid (BALF); Chronic obstructive pulmonary disease; Exhaled breath condensate; Matrix metalloproteinase-12; Tissue inhibitor of metalloproteinase-4.