Elastokines are potentially associated with a poor prognosis in idiopathic pulmonary fibrosis

During the development of idiopathic pulmonary fibrosis (IPF), elastin is broken down and replaced with a stiffer substrate which interferes with normal breathing. This remodeling process releases elastin degradation products (EDPs), or elastokines, into the circulation and act as a surrogate for the degree of matrix turnover. We examined the association between elastokine concentrations with disease severity defined as abnormal lung function and transplant-free survival. Our objective was to determine if EDP concentrations are associated with clinically relevant markers of disease severity in IPF. Concentrations of elastokines were measured via enzyme linked immunosorbent assay (ELISA) from healthy volunteers and those with IPF. Samples were obtained from a single institution's Interstitial Lung Disease (ILD) registry/biorepository (n = 81 with IPF and 24 healthy volunteers). We then used linear and logistic regression modeling, as well as Cox proportional hazard modeling, to assess the association between EDP concentrations at the time of diagnosis, lung function, and clinical outcomes. Patients with IPF were older, more likely to be male, had ever smoked, and had worse lung function compared to healthy volunteers (p value ≤ 0.02 for all parameters). Patients with IPF had higher concentrations of elastokines (p < 0.001), and among those with IPF, higher elastokine concentrations were associated with reduced forced vital capacity (FVC, p = 0.026), and decreased three-year transplant-free survival (p = 0.0005). These findings suggest that elastokines are biomarkers of matrix turnover and are associated with relevant clinical outcomes in patients with IPF.