Review: Serum biomarkers in idiopathic pulmonary fibrosis and systemic sclerosis associated interstitial lung disease – frontiers and horizons

Abstract

Disease behaviour in interstitial lung disease (ILD) is highly variable and accurate clinical tools to predict prognosis and guide management decisions remain unsatisfactorily elusive. Accurate disease stratification would allow clinicians to better distinguish patients at risk of rapid progression requiring urgent treatment, from those indolent disease where potentially toxic drug therapy could be minimised or avoided. Several serum biomarkers have demonstrated potential utility for diagnosis and prognosis of ILD in small retrospective studies, and the hope is future multicentre prospective trials focussed on the markers with most potential will see translation to clinical practice. Two important and contrasting fibrotic lung diseases with high mortality are idiopathic pulmonary fibrosis (IPF) and systemic sclerosis associated ILD (SSc-ILD). In this era where anti-fibrotics for IPF have proven benefit, there are increasing biologic and non-biologic options for the treatment of connective tissue disease ILD (CTD-ILD), and the incidence of both is increasing, there is an urgent need to improve the diagnostic and prognostic accuracy in these complex patients. This comprehensive literature review will summarise and discuss the current evidence for the major candidate serum biomarkers in IPF and SSc-ILD. Biomarkers will be categorised by the following major mechanistic pathways (1) alveolar epithelial cell damage; (2) aberrant fibrogenesis, fibroproliferation and matrix remodelling; (3) immune dysregulation; and (4) vascular and endothelial damage. The aim is to review the rationale, potential and limitations of current candidate biomarkers and their utility in IPF and SSc-ILD to help direct future research and translation to clinical practice.