The diagnostic and prognostic role of MMP-1 and MMP-9 plasma concentrations in idiopathic pulmonary fibrosis
Ioannis Tomos, Aris Spathis, Stylianos Argentos, Anna Karakatsani, Effrosyni D. Manali, Spyros PapirisBackground
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 1 st 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.