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

Abstract

Background 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. Methods Serological 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. Results Increased 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. Conclusion Baseline 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.

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

“…In view of the important contribution of collagen to the mechanical stiffness of pulmonary fibrosis, collagen turnover has naturally become an important means for monitoring disease progression and predicting patient prognosis. Increased concentrations of the collagen degradation markers type 1/3/6 collagen, and C-reactive protein are associated with an increased risk of overall mortality, and elevated levels of the collagen synthesis markers Pro-C3 and Pro-C6 are associated with IPF progression ( Organ et al, 2019 ; Jessen et al, 2021 ).…”

Idiopathic pulmonary fibrosis: Current and future treatment

“…Measures of the serum levels of matrix metalloproteases that break down collagens type I and III using enzyme‐linked immunosorbent assays may lead to a clinically relevant IPF biomarker. 153 As we try new IPF treatment approaches, the importance of accurate, reliable, reasonably priced assays to monitor the efficacy for clinical trial and real‐world application will be increasingly important.…”

The role of precision medicine in interstitial lung disease

“…PROFILE was one such study, which identified SP-D and CA125 as biomarkers that predict disease progression and death in IPF [ 13 ]. Likewise, results from the ongoing Pulmonary Fibrosis Biomarker cohort showed that longitudinal levels of type I and III collagen turnover were associated with progressive disease [ 55 ].…”