Assessment of Matrix Metalloproteinases a Prognostic Indicator in Advanced Fibrotic Lung Disease: A Systematic Review

Abstract

Background: Fibrotic lung diseases were seen to have devastating effects among patients globally. Matrix metalloproteinases (MMP) including MMP-7, MMP-9, and MMP-1 have become promising biomarkers for idiopathic pulmonary fibrosis (IPF), and other fibrotic lung diseases. In this systematic review, the objective was to evaluate their roles in predicting disease severity, progression, and response to treatment to increase diagnostic and prognostic accuracy.

Methods: Following PRISMA guidelines, a systematic search of PubMed, Google Scholar, and Web of Science (January 2014 to December 2024) was conducted. Study screening was conducted using Covidence software and data extraction was performed using Microsoft Excel. Studies with MMP-7, MMP-9, or MMP-1 as potential biomarkers in IPF and fibrotic lung diseases with observed associations with disease outcomes met inclusion criteria. Studies not intended to be original, in focus, or with information that was insufficient in methodology were excluded as exclusion criteria. Qualitative synthesis was conducted based on fifteen studies (n=3,965 participants) that met eligibility criteria, mostly due to methodological heterogeneity. ROBINS-I (Risk of Bias in Non-Randomized Studies of Interventions) tool was used to assess the risk of biasness for each study.

Results:  This systematic review selected 15 studies out of an initial pool of 112 articles. The sample size ranged from 12 to 2,312 participants, with a total of 3,965 participants combined. The MMP-7 was consistently elevated in 73.3% (n=11) of the studies and correlated with disease severity, lung function decline, and progression. In 46.7% (7) of studies, MMP-9 was associated with imaging severity and functional impairments, and in 26.7% (4) of studies, MMP-7 was found as the strongest biomarker, and the correlation coefficient calculated was from (r = 0.65 to 0.80), for MMP-9 it was (r = 0.4 to 0.6) and for MMP-1 (r = 0.3 to 0.45). Direct comparisons were limited by methodological and population variability.

Discussion: MMP-7 seemed to be the most reliable biomarker of disease severity and progression, while MMP-9 and MMP-1 added insights for research into disease mechanisms. Limitations were seen in the small sample size, single-center design, and lack of longitudinal data. Validation of these findings and development of clinical applications would depend on the conduct of larger, multicentre studies.