Start Over

Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis.

Authors :: Tzouvelekis A
Herazo-Maya JD
Slade M
Chu JH
Deiuliis G
Ryu C
Li Q
Sakamoto K
Ibarra G
Pan H
Gulati M
Antin-Ozerkis D
Herzog EL
Kaminski N
Source :: Respirology (Carlton, Vic.) [Respirology] 2017 Apr; Vol. 22 (3), pp. 486-493. Date of Electronic Publication: 2016 Oct 19.
Publication Year :: 2017
Abstract: 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.<br />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).<br />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 <subscript>CO</subscript> ) (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 <subscript>CO</subscript> (r = 0.32, P = 0.001).<br />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.<br /> (© 2016 Asian Pacific Society of Respirology.)