Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study

作者：Gisli R. Jenkins, Juliet K. Simpson, Gauri Saini, Jane H Bentley, Anne‐Marie Russell, Rebecca Braybrooke, Philip L. Molyneaux, Tricia M. McKeever, Athol Umfrey Wells, Aiden A. Flynn, Richard Hubbard, Diana Julie Leeming, Richard P. Marshall, M.A. Karsdal, Pauline T. Lukey, Toby M. Maher · 发表于：The Lancet Respiratory Medicine · 年份：2015 · 被引用次数：326 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Systemic Sclerosis and Related Diseases、Connective Tissue Growth Factor Research

BACKGROUND: Idiopathic pulmonary fibrosis, a progressive and inevitably fatal disorder, has a highly variable clinical course. Biomarkers that reflect disease activity are urgently needed to inform patient management and for use as biomarkers of therapeutic response (theragnostic biomarkers) in clinical trials. We aimed to determine whether dynamic change in markers of extracellular matrix (ECM) turnover predicts progression of idiopathic pulmonary fibrosis as determined by change in forced vital capacity and death. METHODS: In this ongoing prospective, multicentre, observational cohort study (PROFILE), participants with idiopathic pulmonary fibrosis or idiopathic non-specific interstitial pneumonia diagnosed within the preceding 6 months were recruited from two coordinating centres (Nottingham, UK, and, Royal Brompton Hospital, London, UK). Serum samples were prospectively collected at baseline, 1 month, 3 months, and 6 months and were analysed for a panel of novel matrix metalloprotease (MMP)-degraded ECM proteins, by ELISA-based, neoepitope assay. 11 neoepitopes were tested in a discovery cohort of 55 patients to identify biomarkers of sufficient rigour for more detailed analyses. Eight were then further assessed in a validation cohort of 134 patients with 50 age-matched and sex-matched controls. Changes in biomarker concentrations were related to subsequent progression of idiopathic pulmonary fibrosis (defined as death or decline in forced vital capacity >10% at 12 months...