Associations of circulating matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases with clinically relevant outcomes in idiopathic pulmonary fibrosis: Data from the IPF-PRO Registry.

We assessed the prognostic utility of circulating levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry. MMP and TIMP concentrations were quantified by ELISA in plasma from 300 patients. A Cox proportional hazard regression model was used to assess associations between select MMPs and TIMPs and death and disease progression (absolute decline in forced vital capacity ≥10% predicted, death, or lung transplant). Over a median follow-up of 30.4 months, 98 patients died and 182 patients had disease progression. In unadjusted analyses, higher concentrations of MMPs 2, 3, 8 and 9 and TIMPs 1, 2 and 4 were associated with an increased risk of death. MMPs 2 and 8 and TIMP1 remained associated with death after adjustment for clinical factors. In unadjusted analyses, higher concentrations of MMPs 8 and 9 and TIMPs 1 and 4 were associated with an increased risk of disease progression. MMPs 8 and 9 and TIMP1 remained associated with progression after adjustment for clinical factors. Circulating levels of MMP8 and TIMP1 may provide information on the risk of outcomes in patients with IPF not captured by clinical measures.

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Copyright: © 2024 Amubieya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

Olawale Amubieya has nothing to report. Jamie L Todd, Megan L Neely, and Scott M Palmer are employees of the Duke Clinical Research Institute (DCRI), which receives funding support from Boehringer Ingelheim Pharmaceuticals, Inc. to coordinate the IPF-PRO/ILD-PRO Registry. Jamie L Todd reports grants from AstraZeneca, Boehringer Ingelheim, CareDx and has participated on Data Safety Monitoring Boards or Advisory Boards for Altavant Sciences, Natera, Sanofi, Theravance. Megan L Neely reports honoraria for a lecture from North Carolina State University. Robert J Kaner reports grants paid to his institution from Bellerophon, Boehringer Ingelheim, CSL Behring, Genentech, the National Institutes of Health, Respivant, Toray, the US Department of Defense; royalties from UpToDate; fees from AstraZeneca and Galapagos for serving on Adjudication Committees; speaker fees from Boehringer Ingelheim, the France Foundation, Genentech, Vindico; fees for participation on Data Safety Monitoring Boards or Advisory Boards for Boehringer Ingelheim, Genentech, Pliant, PureTech; he holds unpaid leadership or fiduciary roles with the Pulmonary Wellness Foundation and Stony Wold Foundation; holds stock or stock options with Air Cycle Systems and Doximity; he has received medical writing support funded by AstraZeneca, Boehringer Ingelheim, Galapagos, Genentech. Joseph A Lasky has received a research grant pertaining to biomarkers from Boehringer Ingelheim; consulting fees for advisory boards from Roche and Veracyte; speaker fees from Boehringer Ingelheim and Veracyte; participation on Data Safety Monitoring Boards or Advisory Boards for Biogen and Galecto; he is a site investigator for the IPF-PRO Registry. Andrew Namen is a site investigator for the IPF-PRO Registry. Christian Hesslinger is an employee of Boehringer Ingelheim. Scott M Palmer reports research funding to Duke University/DCRI from AstraZeneca, Bristol Myers Squibb, CareDx; royalties or licenses from UpToDate; and speaker fees from Altavant Sciences, Bristol Myers Squibb, Mereo Biopharma, Theravance. S Samuel Weigt reports grants from CareDx; has served on a speaker bureau for Boehringer Ingelheim; and has participated on advisory boards for CareDx, Natera, Theravance, Veracyte. John A Belperio is a member of the Steering Committee for the IPF-PRO/ILD-PRO Registry. This does not alter our adherence to PLOS ONE policies on sharing data and materials.