Local and systemic proteolytic responses in chronic rhinosinusitis with nasal polyposis and asthma.

ABSTRACT

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma coexist frequently and share similar features of inflammation and remodeling. Remodeling has become an important concept in the pathophysiology of asthma and CRSwNP. It happens early in the development of these diseases and is relatively resistant to treatments. The key enzymes responsible for remodeling are matrix metalloproteinases (MMPs). In this study we examined whether asthma and CRSwNP share similar MMP profiles. METHODS: Nasal secretion and serum specimens of controls (19 subjects) and patients with asthma (12), CRSwNP (39), or both (16) were collected between December 2007 and May 2009. Groups were divided into 2 subgroups according to atopy. MMP-7, MMP-9, MMP-13, tissue inhibitors of metalloproteinases (TIMPs), TIMP-1 and TIMP-2, myeloperoxidase (MPO), and human neutrophil elastase (HNE) were measured using enzyme-linked immunosorbent assay (ELISA), and MMP-8 was determined using immunofluorometric assay. High-sensitivity C-reactive protein (hs-CRP) was measured to estimate systemic involvement. RESULTS: Patients with asthma, CRSwNP, or both exhibited lower MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and MPO in nasal secretions (p < 0.05 in CRSwNP) and higher MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and HNE in serum (p < 0.05 in all groups) compared to controls, whereas no difference in MMP-7, MMP-13, TIMP-1, and TIMP-2 were detected. Atopy increased nasal MMP-9 and MPO expression. hs-CRP was higher in patients with CRSwNP and asthma compared to controls. CONCLUSION: Our findings suggest shared pathomechanisms behind asthma and CRSwNP. Contrasting local vs systemic results reflect a different ability of healthy mucosa to react to exogenous stimuli, possibly indicating a protective function of MMP-9 and possibly also MMP-8 in the airways.