Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airflow limitation associated with chronic inflammation involving cytokines and metalloproteinases (MMPs). MMP-8, MMP-9 and neutrophil elastase (NE) are known to be implicated in COPD but the factors influencing activation and suppression remain unclear. This study aimed to compare MMP-8, MMP-9 and NE in the peripheral blood of COPD patients and controls and to likewise assess exhaled breath condensate (EBC) for these MMPs. Peripheral blood micro(mi)RNA139-5p levels, which may regulate MMPs in COPD, were also measured. Blood and EBC were collected from COPD patients (stable and during exacerbations) and healthy controls. Expression of mRNA for MMP-8, MMP-9, NE and miRNA-139-5p expression in peripheral blood mononuclear cells (PBMCs) was measured using qRT-PCR. MMP-8, MMP-9 and NE protein in plasma as well as MMP-8 and MMP-9 protein in EBC were analysed by enzyme-linked immunoassays. PBMCs from COPD patients showed greater expression of mRNA for MMP-8 (p = 0.0004), MMP-9 (p = 0.0023) and NE (p = 0.0019). PBMC expression of mRNA for NE was significantly higher in COPD exacerbations compared to stable cases (p < 0.05). Expression of mRNA for MMP-9 and NE correlated negatively with spirometry in patients (p < 0.05). Plasma from COPD patients showed greater levels of protein for MMP-8 (p = 0.003), MMP-9 (p = 0.046) and NE (p = 0.018). MMP-8 protein levels were lower in the EBC of COPD patients (p < 0.0001). In PBMCs, enhanced expression of mRNA for MMP-9 and NE is associated with COPD and may correlate with disease severity and exacerbations.
Keywords: COPD; MMP-8; MMP-9; exhaled breath condensate; neutrophil elastase.