Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis

Background and objective Idiopathic pulmonary fibrosis ( IPF ) is a progressive disease with poor prognosis and variable clinical course. Although matrix metalloproteinase‐7 ( MMP ‐7) is emerging as an important IPF biomarker, reproducibility across studies is unclear. We aimed to determine whether a previously reported prognostic threshold for MMP ‐7 was predictive of mortality in an independent cohort of IPF patients. Methods MMP ‐7 concentrations obtained from heparinized plasma samples were determined by ELISA in 97 patients with IPF and 41 healthy controls. The association of the previously published heparin plasma MMP ‐7 threshold of 12.1 ng/mL with all‐cause mortality or transplant‐free survival ( TFS ) was determined, either as an independent biomarker or as part of the modified personal clinical and molecular mortality index (m‐ PCMI ). Results MMP ‐7 plasma concentrations were significantly higher in IPF patients compared to healthy controls (14.40 ± 6.55 ng/mL vs 6.03 ± 2.51 ng/mL, P < 0.001). The plasma MMP ‐7 threshold of 12.1 ng/mL was significantly associated with both all‐cause mortality and TFS (unadjusted Cox proportional hazard ratio ( HR ) = 25.85 and 15.49, 95% CI : 10.91–61.23 and 5.41–44.34, respectively, P < 0.001). MMP ‐7 concentrations, split by 12.1 ng/mL, were significantly ( P < 0.05) predictive of mortality and TFS after adjusting for age, gender, smoking and baseline pulmonary function parameters, in a multivariate Cox proportional hazards model. MMP ‐7 concentrations were negatively correlated with diffusing lung capacity of carbon monoxide (DL CO ) (r = −0.21, P = 0.02), and positively with a mortality risk scoring system ( GAP ) that combines age, gender, forced vital capacity ( FVC ) and DL CO (r = 0.32, P = 0.001). Conclusion This study confirms that MMP ‐7 concentrations could be used to accurately predict outcomes across cohorts and centres, when similar collection protocols are applied.