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Peripheral Blood Proteins Predict Mortality in Idiopathic Pulmonary Fibrosis
Open accessAbstract
Rationale: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology with a variable and unpredictable course. Objectives: The aim of this study was to identify and validate plasma proteins that are predictive of outcome in IPF. Methods: Plasma samples were available for 241 patients with IPF (140 derivation and 101 validation). In the derivation cohort, concentrations of 92 proteins were analyzed using a multiplex bead-based immunoassay and concentrations of matrix metalloproteinase (MMP)-7, MMP-1, and surfactant protein D were assessed by ELISA. In the validation cohort concentrations of intercellular adhesion molecule (ICAM)-1, IL-8, and vascular cell adhesion molecule (VCAM)-1 were assessed by bead-based multiplex assay, and S100A12 and MMP-7 by ELISA. Associations of biomarkers with mortality, transplant-free survival, and disease progression were tested in the derivation and validation cohorts using nonparametric methods of survival analysis and the Cox proportional hazards model, and an integrated risk prediction score was derived and tested. Measurements and Main Results: High concentrations of MMP-7, ICAM-1, IL-8, VCAM-1, and S100A12 predicted poor overall survival, poor transplant-free survival, and poor progression-free survival in the derivation cohort. In the independent validation cohort high concentrations of all five were predictive of poor transplant-free survival; MMP-7, ICAM-1, and IL-8 of overall survival; and ICAM-1 of poor progression-free survival. The personal clinical and molecular mortality prediction index derived in the derivation cohort was highly predictive of mortality in the validation cohort. Conclusions: Our results suggest that plasma proteins should be evaluated as a tool for prognosis determination in prioritization of patients for lung transplantation and stratification in drug studies.
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“High plasma concentrations of MMP7, vascular cell adhesion molecule (VCAM)-1, S100A12, intercellular adhesion molecule (ICAM)1, and IL-8 predicted poor overall survival, transplant-free survival, and progression-free survival in an IPF derivation cohort of 141 patients, while all five were predictive of poor transplant-free survival; MMP7, ICAM-1, and IL-8 of over”
From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as Richards et al., 2012
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Additional file 1 of Biomarkers of cellular senescence in idiopathic pulmonary fibrosis
Aversa, Z., Atkinson, E. J., Carmona, E. M., White, T. A., Heeren, A. A., Jachim, S. K., Zhang, X., Cummings, S. R., Chiarella, S. E., LIMPER, A. H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22624408
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Current and Emerging Biomarkers in Interstitial Lung Disease
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Hernandez-Argudo, M., Bordas-Martínez, J., Vicens-Zygmunt, V., Bermudo, G., Suárez-Cuartín, G., del Rio, B., Bolivar, S., Jofré-Grimaldo, H., Llatjós, R., Pijuán, L., et al. (2026) · Respiratory Research · doi:10.1186/s12931-026-03678-3
Tomos, I. P., Spathis, A., Argentos, S., Karakatsani, A., Manali, E. D., & Papiris, S. A. (2026) · Therapeutic Advances in Respiratory Disease · doi:10.1177/17534666261493434
Metadata
- Authors
- Richards, T. J., Kaminski, N., Baribaud, F., Flavin, S., Brodmerkel, C., Horowitz, D., Li, K., Choi, J., Vuga, L. J., Lindell, K. O., Klesen, M., Zhang, Y., & Gibson, K. F.
- Affiliations
- University of Pittsburgh (US)
- Centocor R&D Inc., Radnor, Pennsylvania
- Corresponding author
- Gibson, Kevin F.
- ORCID
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-01-01
- Volume
- 185
- Issue
- 1
- Pages
- 67-76
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- PMC
- PMC3262037
- OpenAlex
- W2007414618
- Cited by
- 381
- References
- 67
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 18 · 2023: 26 · 2022: 20 · 2021: 23 · 2020: 27 · 2019: 22 · 2018: 31 · 2017: 30 · 2016: 27 · 2015: 40 · 2014: 30 · 2013: 35 · 2012: 28
- FWCI
- 25.85
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P50 HL0894932, R01HL095397)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- idiopathic pulmonary fibrosis, plasma biomarkers, mortality prediction, MMP-7, ICAM-1, interleukin-8, VCAM-1, S100A12, surfactant protein D, transplant-free survival, progression-free survival, risk scoring, disease progression
- MeSH terms
- S100A12 Protein, Aged, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, S100 Proteins, Predictive Value of Tests, Cohort Studies, Biomarkers, Cell Adhesion Molecules, Proportional Hazards Models, Survival Analysis, Interleukin-8, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Matrix Metalloproteinase 1, Matrix Metalloproteinases, Matrix Metalloproteinase 7, Idiopathic Pulmonary Fibrosis
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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