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.
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: Thomas J Richards; Naftali Kaminski; Fred Baribaud; Susan Flavin; Carrie Brodmerkel; Daniel Horowitz; Katherine Li; Jiin Choi; Louis J Vuga; Kathleen O Lindell; Melinda Klesen; Yingze Zhang; Kevin F Gibson Journal: Am J Respir Crit Care Med Date: 2012-01-01 Impact factor: 21.405
Authors: Charlotte J Morrison; Georgina S Butler; David Rodríguez; Christopher M Overall Journal: Curr Opin Cell Biol Date: 2009-07-16 Impact factor: 8.382
Authors: Ganesh Raghu; Derek Weycker; John Edelsberg; Williamson Z Bradford; Gerry Oster Journal: Am J Respir Crit Care Med Date: 2006-06-29 Impact factor: 21.405
Authors: K E Greene; T E King; Y Kuroki; B Bucher-Bartelson; G W Hunninghake; L S Newman; H Nagae; R J Mason Journal: Eur Respir J Date: 2002-03 Impact factor: 16.671
Authors: Brett Ley; Christopher J Ryerson; Eric Vittinghoff; Jay H Ryu; Sara Tomassetti; Joyce S Lee; Venerino Poletti; Matteo Buccioli; Brett M Elicker; Kirk D Jones; Talmadge E King; Harold R Collard Journal: Ann Intern Med Date: 2012-05-15 Impact factor: 25.391
Authors: Ivan O Rosas; Thomas J Richards; Kazuhisa Konishi; Yingze Zhang; Kevin Gibson; Anna E Lokshin; Kathleen O Lindell; Jose Cisneros; Sandra D Macdonald; Annie Pardo; Frank Sciurba; James Dauber; Moises Selman; Bernadette R Gochuico; Naftali Kaminski Journal: PLoS Med Date: 2008-04-29 Impact factor: 11.069
Authors: Tasha E Fingerlin; Elissa Murphy; Weiming Zhang; Anna L Peljto; Kevin K Brown; Mark P Steele; James E Loyd; Gregory P Cosgrove; David Lynch; Steve Groshong; Harold R Collard; Paul J Wolters; Williamson Z Bradford; Karl Kossen; Scott D Seiwert; Roland M du Bois; Christine Kim Garcia; Megan S Devine; Gunnar Gudmundsson; Helgi J Isaksson; Naftali Kaminski; Yingze Zhang; Kevin F Gibson; Lisa H Lancaster; Joy D Cogan; Wendi R Mason; Toby M Maher; Philip L Molyneaux; Athol U Wells; Miriam F Moffatt; Moises Selman; Annie Pardo; Dong Soon Kim; James D Crapo; Barry J Make; Elizabeth A Regan; Dinesha S Walek; Jerry J Daniel; Yoichiro Kamatani; Diana Zelenika; Keith Smith; David McKean; Brent S Pedersen; Janet Talbert; Raven N Kidd; Cheryl R Markin; Kenneth B Beckman; Mark Lathrop; Marvin I Schwarz; David A Schwartz Journal: Nat Genet Date: 2013-04-14 Impact factor: 38.330
Authors: Ayodeji Adegunsoye; Shehabaldin Alqalyoobi; Angela Linderholm; Willis S Bowman; Cathryn T Lee; Janelle Vu Pugashetti; Nandini Sarma; Shwu-Fan Ma; Angela Haczku; Anne Sperling; Mary E Strek; Imre Noth; Justin M Oldham Journal: Chest Date: 2020-05-22 Impact factor: 9.410
Authors: Hilary F Armstrong; Anna J Podolanczuk; R Graham Barr; Elizabeth C Oelsner; Steven M Kawut; Eric A Hoffman; Russell Tracy; Naftali Kaminski; Robyn L McClelland; David J Lederer Journal: Am J Respir Crit Care Med Date: 2017-11-15 Impact factor: 30.528
Authors: Carina Kärrman Mårdh; James Root; Mohib Uddin; Kristina Stenvall; Anna Malmgren; Kostas Karabelas; Matthew Thomas Journal: J Immunol Res Date: 2017-05-15 Impact factor: 4.818
Authors: Mohamed F Ali; Harika Dasari; Virginia P Van Keulen; Divi Cornec; George Vasmatzis; Tobias Peikert; Eva M Carmona Journal: Sci Rep Date: 2017-06-20 Impact factor: 4.379
Authors: Jose D Herazo-Maya; Jiehuan Sun; Philip L Molyneaux; Qin Li; Julian A Villalba; Argyrios Tzouvelekis; Heather Lynn; Brenda M Juan-Guardela; Cristobal Risquez; Juan C Osorio; Xiting Yan; George Michel; Nachelle Aurelien; Kathleen O Lindell; Melinda J Klesen; Miriam F Moffatt; William O Cookson; Yingze Zhang; Joe G N Garcia; Imre Noth; Antje Prasse; Ziv Bar-Joseph; Kevin F Gibson; Hongyu Zhao; Erica L Herzog; Ivan O Rosas; Toby M Maher; Naftali Kaminski Journal: Lancet Respir Med Date: 2017-09-21 Impact factor: 30.700