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An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study

Maher, Toby M.; Oballa, Eunice; Simpson, Juliet K.; Porte, Joanne; Habgood, Anthony; Fahy, William A; Flynn, Aiden; Molyneux, Philip L.; Braybrooke, Rebecca; Divyateja, Hrushikesh; Parfrey, Helen; Rassl, Doris; Russell, Anne-Marie; Saini, Gauri; Renzoni, Elisabetta; Duggan, Anne-Marie; Hubbard, Richard; Wells, Athol U; Lukey, Pauline T.; Marshall, Richard P.; Jenkins, R. Gisli

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Authors

Toby M. Maher

Eunice Oballa

Juliet K. Simpson

Joanne Porte

Anthony Habgood

William A Fahy

Aiden Flynn

Philip L. Molyneux

Rebecca Braybrooke

Hrushikesh Divyateja

Helen Parfrey

Doris Rassl

Anne-Marie Russell

Gauri Saini

Elisabetta Renzoni

Anne-Marie Duggan

RICHARD HUBBARD richard.hubbard@nottingham.ac.uk
Blf/Gsk Professor of Epidemiological Resp Research

Athol U Wells

Pauline T. Lukey

Richard P. Marshall

R. Gisli Jenkins



Abstract

Background: Idiopathic Pulmonary Fibrosis (IPF) is a progressive, fatal condition with a variable disease trajectory. The aim of this study was to evaluate potential biomarkers that predict outcome for people with IPF.
Method: The PROFILE study is a large prospective longitudinal cohort of treatment naïve IPF patients. We adopted a two-stage discovery and validation design using the PROFILE cohort. For the discovery analysis 106 individuals were examined alongside 50 age and gender matched healthy controls. We undertook an unbiased, multiplex evaluation of 123 biomarkers. Promising, novel, markers were further evaluated by immunohistochemical assessment of IPF lung tissue. The validation analysis examined samples from 206 IPF subjects, from the remaining 212 IPF patients recruited to PROFILE Central England, and were used for replication of the biomarkers identified from the discovery analysis using singleplex assays. This study addressed the predictive power of selected biomarkers to identify individuals with IPF at risk of: 1) progression and 2) death. The PROFILE studies are registered on clinicaltrials.gov (PROFILE Central England NCT01134822; PROFILE Royal Brompton Hospital NCT01110694).
Findings: The discovery analysis identified four serum biomarkers (Surfactant Protein D, Matrix Metalloproteinase 7, CA19-9 and CA-125) suitable for replication. Histological assessment of CA19-9 and CA-125 established these proteins as markers of epithelial damage. Replication analysis confirmed that baseline values of SP-D (46.6ng/ml vs 34.6 ng/ml; p =0.002) and CA19-9 (53.7 U/ml vs 22.2 U/ml p

Citation

Maher, T. M., Oballa, E., Simpson, J. K., Porte, J., Habgood, A., Fahy, W. A., …Jenkins, R. G. (in press). An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study. Lancet Respiratory Medicine, 5(12), https://doi.org/10.1016/S2213-2600%2817%2930430-7

Journal Article Type Article
Acceptance Date Oct 4, 2017
Online Publication Date Nov 14, 2017
Deposit Date Nov 22, 2017
Publicly Available Date Mar 29, 2024
Journal Lancet Respiratory Medicine
Print ISSN 2213-2600
Electronic ISSN 2213-2619
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 5
Issue 12
DOI https://doi.org/10.1016/S2213-2600%2817%2930430-7
Keywords Interstitial lung disease, clinical trials, biomarker,
Public URL https://nottingham-repository.worktribe.com/output/894490
Publisher URL http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30430-7/fulltext

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