Peripheral Blood Proteins Predict Mortality in Idiopathic Pulmonary Fibrosis.
Am J Respir Crit Care Med. 2011 Oct 20;
Authors: Richards TJ, Kaminski N, Baribaud F, Flavin S, Brodmerkel C, Horowitz D, Li K, Choi J, Vuga LJ, Lindell KO, Klesen M, Zhang Y, Gibson KF
Introduction/ BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology with a variable and unpredictable course. 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 IPF patients (140 - derivation and 101 validation). In derivation cohort, concentrations of 92 proteins were analyzed using a multiplex bead-based immunoassay and concentrations of MMP7, MMP1, and SPD were assessed by ELISA. In the validation cohort concentrations of ICAM1, IL8, VCAM1 were assessed by bead-based multiplex assay, and S100A12 and MMP7 by ELISA. Associations of biomarkers with mortality, transplant free survival, and disease progression were tested in 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. RESULTS: High concentrations of MMP7, ICAM1, IL8, VCAM1, 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, MMP7, ICAM1, and IL8 of overall survival and ICAM1 of poor progression free survival. The personal clinical and molecular mortality prediction index (PCMI) 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.
PMID: 22016448 [PubMed - as supplied by publisher]