Cited by 383Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisOccupational and environmental lung diseasesTransplantation: Methods and Outcomes

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Peripheral Blood Proteins Predict Mortality in Idiopathic Pulmonary Fibrosis

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Richards, Thomas J., Kaminski, Naftali, Baribaud, Fred, Flavin, Susan, Brodmerkel, Carrie, Horowitz, Daniel, Li, Katherine, Choi, Jiin, Vuga, Louis J., Lindell, Kathleen O., Klesen, Melinda, Zhang, Yingze, Gibson, Kevin F.·2012·American Journal of Respiratory and Critical Care Medicine

DOI 10.1164/rccm.201101-0058ocPMC PMC3262037

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Abstract

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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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: Richards, Thomas J.
Kaminski, Naftali
Flavin, Susan
Li, Katherine
Lindell, Kathleen O.
Zhang, Yingze
Gibson, Kevin F.
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
DOI: 10.1164/rccm.201101-0058oc
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
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
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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Peripheral Blood Proteins Predict Mortality in Idiopathic Pulmonary Fibrosis

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