MMP-7 as a non-invasive biomarker in interstitial lung diseases and other chronic respiratory diseases: a narrative review

Abstract

Interstitial lung diseases (ILDs) are a heterogeneous group of disorders in which epithelial injury, inflammation and fibrosis lead to progressive loss of lung function. Several ILDs other than idiopathic pulmonary fibrosis (IPF), including connective tissue disease-associated ILD (CTD-ILD), fibrotic hypersensitivity pneumonitis and fibrotic nonspecific interstitial pneumonia, may develop a progressive fibrosing phenotype, and distinguishing fibrotic from non-fibrotic disease is clinically important. Matrix metalloproteinase-7 (MMP-7), a circulating biomarker of extracellular matrix remodeling, epithelial injury and inflammation, has been investigated as a non-invasive marker of fibrosing lung disease, but the evidence remains fragmented and unsynthesized. To summarize current evidence on the diagnostic and prognostic value of MMP-7 in interstitial lung diseases and other chronic respiratory diseases, with particular emphasis on fibrosing lung disorders. A narrative review was performed using PubMed/MEDLINE, Scopus and Web of Science. Search terms combined “MMP-7” and “matrix metalloproteinase-7” with terms for interstitial lung disease, CTD-ILD, fibrotic lung diseases, sarcoidosis, hypersensitivity pneumonitis, progressive pulmonary fibrosis, organizing pneumonia and chronic respiratory diseases. Studies were selected on their evaluation of the diagnostic, prognostic or monitoring role of MMP-7. In IPF, MMP-7 shows strong diagnostic and prognostic performance and is associated with disease severity, functional decline and mortality. Elevated levels are consistently reported in CTD-ILD, particularly systemic sclerosis- and rheumatoid arthritis-associated ILD, where they correlate with impaired pulmonary function, radiological fibrosis and disease activity. Increased concentrations have also been described in fibrotic hypersensitivity pneumonitis, fibrotic nonspecific interstitial pneumonia and organizing pneumonia, with conflicting findings in sarcoidosis and chronic obstructive pulmonary disease and limited or predominantly experimental data in asthma and bronchiectasis, where elevation reflects epithelial injury and airway remodeling rather than disease-specific pathology. Across these disorders MMP-7 mirrors shared pathways of epithelial damage and matrix turnover, supporting its potential utility in diagnosis and risk stratification, while its value for monitoring disease activity or treatment response remains unproven. MMP-7 is best regarded as a marker of active fibrotic remodeling rather than of any single disease, with its clearest value in fibrosing ILD and within multimarker strategies rather than as a standalone test.