Glycosaminoglycans significantly correlate with matrix metalloproteinases during exacerbations of COPD

Background: Exacerbations of COPD (ECOPD) accelerate the deterioration of lung function, affecting the quality of life of COPD patients and moreover, remain a major cause of mortality and morbidity. Glycosaminoglycans (GAGs) are essential extracellular matrix (ECM) molecules that regulate the viscoelastic and biomechanical properties of the lung. Matrix metalloproteinases (MMPs) are involved in the cleavage of ECM and COPD pathogenesis. Aims and objectives: The aim of our study was to compare the levels of GAGs and MMPs in the bronchoalveolar lavage (BAL) from patients with ECOPD and patients with stable disease (SCOPD) and furthermore, to investigate possible correlations in the expression of these molecules in BAL. Methods: We included 97 COPD patients diagnosed with either stable disease (SCOPD) (n=53) or AECOPD (n=44), undergoing diagnostic bronchoscopy. Hyaluronic acid (HA), chondroitin sulfate (CS), heparan sulfate (HS) and MMP-2, MMP-9, and MMP-12 were measured in BAL by ELISA. Results: HA, CS, HS and MMP-9 were significantly elevated in BAL of patients with AECOPD as compared to SCOPD (p=0.002, p=0.049, p=0.031, and p=0.012. respectively). MMP-9 and MMP-12 were negatively correlated with FEV1% pred (p=0.031, p=0.002 and p=0.015, respectively) while CS was positively correlated with FEV1% pred (p=0.030). Furthermore, HA, CS and HS were significantly correlated with MMP-2, MMP-9 and MMP-12. Conclusions: The observed correlation between MMPs and GAGs in the BAL of patients with ECOPD and SCOPD indicate that these two group of molecules may interact with each other resulting in airway remodeling leading to lung function decline during exacerbations of COPD.