Associations of circulating matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases with clinically relevant outcomes in idiopathic pulmonary fibrosis: Data from the IPF-PRO Registry

PLoS One. 2024 Oct 17;19(10):e0312044. doi: 10.1371/journal.pone.0312044. eCollection 2024.

Abstract

Introduction: We assessed the prognostic utility of circulating levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry.

Methods: MMP and TIMP concentrations were quantified by ELISA in plasma from 300 patients. A Cox proportional hazard regression model was used to assess associations between select MMPs and TIMPs and death and disease progression (absolute decline in forced vital capacity ≥10% predicted, death, or lung transplant).

Results: Over a median follow-up of 30.4 months, 98 patients died and 182 patients had disease progression. In unadjusted analyses, higher concentrations of MMPs 2, 3, 8 and 9 and TIMPs 1, 2 and 4 were associated with an increased risk of death. MMPs 2 and 8 and TIMP1 remained associated with death after adjustment for clinical factors. In unadjusted analyses, higher concentrations of MMPs 8 and 9 and TIMPs 1 and 4 were associated with an increased risk of disease progression. MMPs 8 and 9 and TIMP1 remained associated with progression after adjustment for clinical factors.

Conclusion: Circulating levels of MMP8 and TIMP1 may provide information on the risk of outcomes in patients with IPF not captured by clinical measures.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Disease Progression*
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis* / blood
  • Idiopathic Pulmonary Fibrosis* / mortality
  • Male
  • Matrix Metalloproteinases* / blood
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Registries*
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tissue Inhibitor of Metalloproteinases* / blood

Substances

  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinases
  • Biomarkers
  • Tissue Inhibitor of Metalloproteinase-1
  • TIMP1 protein, human

Grants and funding

The IPF-PRO Registry is supported by Boehringer Ingelheim Pharmaceuticals, Inc and run in collaboration with the Duke Clinical Research Institute and enrolling centers. Boehringer Ingelheim was involved in the design of the study, the interpretation of the data and the development of the manuscript.