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Peer-reviewedCC BY-NC 4.0Therapeutic Advances in Respiratory Disease

The diagnostic and prognostic role of MMP-1 and MMP-9 plasma concentrations in idiopathic pulmonary fibrosis

  • Ioannis Tomos1
  • Aris Spathis2
  • Stylianos Argentos3
  • Anna Karakatsani4
  • Effrosyni D. Manali4
  • Spyros Papiris4
4 affiliations
  1. 15th Pulmonary Medicine Department, SOTIRIA Chest Diseases Hospital of Athens, Athens, Greece
  2. 2Department of Cytopathology, School of Medicine, National and Kapodistrian University of Athens, “ATTIKON” University Hospital, Athens, Greece
  3. 32nd Department of Radiology, ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece
  4. 42nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, “ATTIKON” University Hospital, Athens, Greece
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Abstract

Background: Idiopathic pulmonary fibrosis (IPF) represents a chronic and irreversible progressive disease, while acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) represents a catastrophic event in the course of the disease with high mortality. So far, there is no known accurate biomarker with a diagnostic or prognostic role in IPF. Matrix metalloproteases (MMPs), belonging to the family of zinc-containing metallopeptidases, play an active role in extracellular matrix remodeling and in regulating fibrogenesis.

Objectives: The study’s aim was to assess the potential diagnostic and prognostic role of plasma MMP-1 and MMP-9 in IPF and their association to disease progression, acute exacerbation development, and death.

Design: Consecutive stable and exacerbated patients referred to our department from October 2013 until December 2017 were enrolled in the study.

Methods: Demographic, clinical, and laboratory data were collected. MMP-1 and MMP-9 plasma concentrations were measured. All patients were followed-up until death or until 1st July 2020. We analyzed data using tobit regression analysis, Kaplan-Meier analysis, Cox regression analysis, and fractional polynomials.

Results: One hundred twenty-eight patients were included in the study [74 stable IPF patients, mean age (SD) 71.5 years (8.05) and 54 exacerbated, mean age (SD) 71.8 years (10.15)] as well as 26 healthy controls, mean age (SD) 61.4 years (10.4). At baseline, both stable IPF and exacerbated patients presented higher concentrations of MMP-9 in plasma compared to healthy controls independently of age, sex, and smoking (p=0.006 and p=0.002, respectively). In stable IPF, each 1 µg/L increase in plasma MMP-1 concentration at baseline was associated with an increase in the hazard rate of death by 20% (95%CI: 2% to 42%; adjusted for age, sex, smoking and FVC).

Conclusion: In our patients with stable IPF, MMP-1 concentration is prognostic for death, whereas MMP-9 has diagnostic value for IPF. These results may lead to better patient stratification and personalized therapeutic approaches.

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Cite

BibTeXRIS
BibTeX
@article{tomos2026diagnostic,
  title = {{The diagnostic and prognostic role of MMP-1 and MMP-9 plasma concentrations in idiopathic pulmonary fibrosis}},
  author = {Ioannis Tomos and Aris Spathis and Stylianos Argentos and Anna Karakatsani and Effrosyni D. Manali and Spyros Papiris},
  journal = {Therapeutic Advances in Respiratory Disease},
  year = {2026},
  month = sep,
  doi = {10.1177/17534666261493434},
  url = {https://doi.org/10.1177/17534666261493434},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - The diagnostic and prognostic role of MMP-1 and MMP-9 plasma concentrations in idiopathic pulmonary fibrosis
AU  - Ioannis Tomos
AU  - Aris Spathis
AU  - Stylianos Argentos
AU  - Anna Karakatsani
AU  - Effrosyni D. Manali
AU  - Spyros Papiris
PY  - 2026
DA  - 2026/09/28
JO  - Therapeutic Advances in Respiratory Disease
DO  - 10.1177/17534666261493434
UR  - https://doi.org/10.1177/17534666261493434
AB  - Background: Idiopathic pulmonary fibrosis (IPF) represents a chronic and irreversible progressive disease, while acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) represents a catastrophic event in the course of the disease with high mortality. So far, there is no known accurate biomarker with a diagnostic or prognostic role in IPF. Matrix metalloproteases (MMPs), belonging to the family of zinc-containing metallopeptidases, play an active role in extracellular matrix remodeling and in regulating fibrogenesis.  Objectives: The study’s aim was to assess the potential diagnostic and prognostic role of plasma MMP-1 and MMP-9 in IPF and their association to disease progression, acute exacerbation development, and death.  Design: Consecutive stable and exacerbated patients referred to our department from October 2013 until December 2017 were enrolled in the study.  Methods: Demographic, clinical, and laboratory data were collected. MMP-1 and MMP-9 plasma concentrations were measured. All patients were followed-up until death or until 1st July 2020. We analyzed data using tobit regression analysis, Kaplan-Meier analysis, Cox regression analysis, and fractional polynomials.  Results: One hundred twenty-eight patients were included in the study [74 stable IPF patients, mean age (SD) 71.5 years (8.05) and 54 exacerbated, mean age (SD) 71.8 years (10.15)] as well as 26 healthy controls, mean age (SD) 61.4 years (10.4). At baseline, both stable IPF and exacerbated patients presented higher concentrations of MMP-9 in plasma compared to healthy controls independently of age, sex, and smoking (p=0.006 and p=0.002, respectively). In stable IPF, each 1 µg/L increase in plasma MMP-1 concentration at baseline was associated with an increase in the hazard rate of death by 20% (95%CI: 2% to 42%; adjusted for age, sex, smoking and FVC).  Conclusion: In our patients with stable IPF, MMP-1 concentration is prognostic for death, whereas MMP-9 has diagnostic value for IPF. These results may lead to better patient stratification and personalized therapeutic approaches.
SN  - 1753-4658
SN  - 1753-4666
ER  -