Matrix metalloproteinases and chronic rhinosinusitis with nasal polyposis. Unravelling a puzzle through a systematic review

BACKGROUND: The expression of metalloproteinases (MMPs) in chronic rhinosinusitis with nasal polyposis (CRSwNP) was reviewed in order to investigate their possible use as therapeutical targets and/or biomarkers. METHODOLOGY: The differences between CRSwNP and normal controls or CRS without NP, as well as the effects of various treatments on MMPs, tissue inhibitors of MMPs (TIMPs) and MMP/TIMP ratios were considered as primary outcomes. Additional factors reported to affect MMP expression levels were noted as secondary outcomes. Data regarding inflammatory subtypes, patients’ clinical characteristics, controls, laboratory method(s) and origin of samples were also pooled. Studies on 10 or fewer patients or on specimens other than nasal and serum were excluded. RESULTS: Forty-three studies were included. Tissue sample origin, allergic rhinitis, smoking, infection, medication intake and primary or recurrent disease should be considered as confounding factors for MMP levels. MMP-1 and -7 were consistently found to be significantly higher in CRSwNP patients than controls. CRSwNP endotypes with distinctly different inflammation patterns seem to present similar MMP-related remodelling patterns. CONCLUSIONS: The existing literature has revealed several population and methodology related confounding factors and remains inconclusive regarding the roles of MMPs in CRSwNP pathophysiology and their possible clinical usefulness as biomarkers and therapeutical targets.