Researchers Find New Potential Biomarkers Associated With Idiopathic Pulmonary Fibrosis Progression

A study recently published in the journal Lancet Respiratory Medicine revealed a novel set of potential biomarkers that can be used as predictors of idiopathic pulmonary fibrosis (IPF) disease progression. The study is entitled “Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study” and was developed by researchers at the University of Nottingham, GlaxoSmithKline, the Royal Brompton Hospital, Imperial College in the United Kingdom and Nordic Bioscience in Denmark.

IPF is a fatal, rare lung disease in which the alveoli and lung tissues are damaged, turning thick and scarred (fibrosis), compromising oxygen transfer between the lungs and the bloodstream. IPF can have a highly variable clinical course, characterized by a shortness of breath (dyspnea) that gradually worsens and a persistent cough. There is no cure for the disease and respiratory failure is the main cause of death. IPF has a poor prognosis and the majority of the patients live three to five years after being diagnosed.

There is an urgent need to establish biomarkers that allow the assessment of IPF disease activity and the therapeutic response (theragnostic biomarkers) in clinical trials. The goal of the research team was to evaluate whether turnover changes of the markers of the extracellular matrix (ECM), namely in metalloprotease-degraded ECM proteins, could be used as predictors of IPF disease progression based on altered forced vital capacity (decline >10%) and death.

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Researchers conducted an ongoing prospective, multicenter, observational cohort study (PROFILE), with 189 patients diagnosed with IPF from two coordinating centers (Nottingham and Royal Brompton Hospital in the United Kingdom), between September 2010 and March 2012. Serum samples from the participants were collected at baseline, 1, 3 and 6 months and were assessed for a set of eight novel matrix metalloprotease-degraded ECM proteins, which correspond to ECM protein fragments (also called neoepitopes) formed by the activity of metalloproteinases.

Researchers found that the mean concentrations of these specific biomarkers is increased in IPF patients in comparison with healthy controls, and that they correlated with IPF disease progression, where six neoepitopes (C1M, C3A, C3M, C6M, CRPM and VICM) had higher baseline levels in IPF patients with progressive disease in comparison with those who had a stable disease. The same finding was observed after 6 months, although the concentration of the neoepitope BGM, instead of VICM, was found to be significantly higher in patients with progressive IPF. The baseline concentration of two neoepitopes (C1M and C3A) was found to be associated with increased mortality. Researchers also found that the rate of change of six neoepitopes (BGM, C1M, C3M, C5M, C6M and CRPM) between baseline levels and after 3 months was a strong predictor of poorer overall survival. Of these six, the strongest correlation with decreased survival was found with the CRPM neoepitope.

The research team concluded that neoepitope concentration can be used as a biomarker for IPF and help in the management of the disease. “We believe that these neoepitopes have the potential to address an urgent unmet need in the management of idiopathic pulmonary fibrosis,” concluded the research team. “Increasing concentrations of matrix neoepitopes could identify a phenotype of idiopathic pulmonary fibrosis characterized by rapid matrix turnover and poor prognosis, which might be more amenable to antifibrotic therapy.”

More information on the clinical trials of the PROFILE study can be found through the codes NCT01134822 and NCT01110694.