Peripheral blood proteins predict mortality in idiopathic pulmonary fibrosis
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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, VCAM-1, S100A12, ICAM-1, and IL-8 predicted poor overall survival, transplant-free survival, and progression-free survival in an IPF derivation cohort of 141 patients, with some predictive associations in a validation cohort of 101 subjects.
“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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Karampitsakos, Τ., Torrisi, S. E., Antoniou, K. M., Manali, E. D., Korbila, I. P., Παπαϊωάννου, Ο., Sampsonas, F., Katsaras, M., Vasarmidi, E., Papakosta, D., et al. (2021) · Respiratory Research · doi:10.1186/s12931-021-01725-9 · Cited by 69 · see citing works
Alteration of human macrophage phenotypes by the anti-fibrotic drug nintedanib
Bellamri, N., Morzadec, C., Joannes, A., Lecureur, V., Wollin, L., Jouneau, S., & Vernhet, L. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.03.061 · Cited by 68 · see citing works
Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis
Wilkes, D. S., Chew, T., Flaherty, K. R., Frye, S. B., Gibson, K. F., Kaminski, N., Klemsz, M. J., Lange, W., Noth, I., & Rothhaar, K. (2015) · European Respiratory Journal · doi:10.1183/09031936.00105314 · Cited by 67 · see citing works
Self-citation
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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