Turnover of type I and III collagen predicts progression of idiopathic pulmonary fibrosis

H Jessen,M A Karsdal,J M B Sand,S B Shaker,P Frederiksen,E Bendstrup,D J Leeming,T S Prior,N Hoyer

doi:10.1186/s12931-021-01801-0

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF.MethodsSerological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not.ResultsIncreased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics.ConclusionBaseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.

Highlights

Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate
The objectives of this study were to investigate (1) type I and III collagen turnover measured at baseline as prognostic biomarkers for disease progression at 12 months, (2) longitudinal assessment of type I and III collagen turnover in stable and progressive IPF patients during a 1-year period, and (3) whether antifibrotic therapy has an impact on type I and III collagen turnover
Nintedanib and pirfenidone have been available during the entire study period and the choice of which to prescribe was made by the treating clinician based on the side effect profile discussed with the patients

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF. Idiopathic pulmonary fibrosis (IPF) is characterized by its unknown aetiology and poor prognosis [1, 2]. The heterogeneous rate of disease progression complicates the prediction of disease course for individual patients [3,4,5]. From a management and therapeutic perspective of IPF, an unfulfilled clinical need is a requirement to distinguish patients with more stable disease from those at higher risk of disease progression. Biomarkers that could identify patients at high risk of disease progression or stratify patients into groups more

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