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Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis.
Respirology. 2017 04; 22(3):486-493.R

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.

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 (DLCO) (r = -0.21, P = 0.02), and positively with a mortality risk scoring system (GAP) that combines age, gender, forced vital capacity (FVC) and DLCO (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.

Authors+Show Affiliations

Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Department of Occupational and Environmental Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, USA.

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

27761978

Citation

Tzouvelekis, Argyris, et al. "Validation of the Prognostic Value of MMP-7 in Idiopathic Pulmonary Fibrosis." Respirology (Carlton, Vic.), vol. 22, no. 3, 2017, pp. 486-493.
Tzouvelekis A, Herazo-Maya JD, Slade M, et al. Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis. Respirology. 2017;22(3):486-493.
Tzouvelekis, A., Herazo-Maya, J. D., Slade, M., Chu, J. H., Deiuliis, G., Ryu, C., Li, Q., Sakamoto, K., Ibarra, G., Pan, H., Gulati, M., Antin-Ozerkis, D., Herzog, E. L., & Kaminski, N. (2017). Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis. Respirology (Carlton, Vic.), 22(3), 486-493. https://doi.org/10.1111/resp.12920
Tzouvelekis A, et al. Validation of the Prognostic Value of MMP-7 in Idiopathic Pulmonary Fibrosis. Respirology. 2017;22(3):486-493. PubMed PMID: 27761978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis. AU - Tzouvelekis,Argyris, AU - Herazo-Maya,Jose D, AU - Slade,Martin, AU - Chu,Jen-Hwa, AU - Deiuliis,Giuseppe, AU - Ryu,Changwan, AU - Li,Qin, AU - Sakamoto,Koji, AU - Ibarra,Gabriel, AU - Pan,Hongyi, AU - Gulati,Mridu, AU - Antin-Ozerkis,Danielle, AU - Herzog,Erica L, AU - Kaminski,Naftali, Y1 - 2016/10/19/ PY - 2016/02/23/received PY - 2016/07/29/revised PY - 2016/08/06/accepted PY - 2016/10/21/pubmed PY - 2017/12/2/medline PY - 2016/10/21/entrez KW - heparin plasma KW - idiopathic pulmonary fibrosis KW - matrix metalloproteinase-7 KW - prognostic biomarker SP - 486 EP - 493 JF - Respirology (Carlton, Vic.) JO - Respirology VL - 22 IS - 3 N2 - 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 (DLCO) (r = -0.21, P = 0.02), and positively with a mortality risk scoring system (GAP) that combines age, gender, forced vital capacity (FVC) and DLCO (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. SN - 1440-1843 UR - https://www.unboundmedicine.com/medline/citation/27761978/Validation_of_the_prognostic_value_of_MMP_7_in_idiopathic_pulmonary_fibrosis_ L2 - https://doi.org/10.1111/resp.12920 DB - PRIME DP - Unbound Medicine ER -