Biomarkers of collagen formation are predictive of IPF progression and death

Background: Extracellular matrix (ECM) remodeling is a key component of idiopathic pulmonary fibrosis (IPF). Biomarkers reflecting formation of type III (PRO-C3) and type VI (PRO-C6) collagen may provide valuable information on disease progression. We have investigated whether these biomarkers are related to progression of disease and death in IPF patients. Methods: 184 IPF patients from the prospective Danish PFBIO-cohort had biomarkers measured at the time of diagnosis, before initiation of antifibrotic treatment, and were followed for up to 3 years. Progression was defined as FVC decline > 10% and/or DLCO decline > 15% at any time. Results: IPF patients had higher levels of PRO-C3 and PRO-C6 compared to the normal range. A logistic regression showed baseline PRO-C3 levels to be associated with a combined endpoint of progression or death at 6 months (p=0.005) and 12 months (p=0.048). Baseline PRO-C6 levels were associated with progression or death at 6 months (p=0.031). In Cox proportional hazards analysis, baseline PRO-C3 levels were associated with an increased mortality during follow-up (HR: 2.32, p=0.003), while this was not found for baseline PRO-C6 levels (HR: 1.8, p=0.192). Conclusions: PRO-C3 and, to a lesser extent, PRO-C6 measured at the time of diagnosis were able to predict disease progression and death for IPF patients. These markers of ECM formation could be useful to identify the patient in most need of treatment.