Diagnostic and Prognostic Biomarkers for Chronic Fibrosing Interstitial Lung Diseases With a Progressive Phenotype

Biomarkers have the potential to become central to the clinical evaluation and monitoring of patients with chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype. Here we summarize the current understanding of putative serum, BAL fluid, and genetic biomarkers in this setting, according to their hypothesized pathobiologic mechanisms: evidence of epithelial cell dysfunction (eg, Krebs von den Lungen-6 antigen), fibroblast proliferation and extracellular matrix production or turnover (eg, matrix metalloproteinase-1), or immune dysregulation (eg, CC chemokine ligand 18). While most of the available data come from idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrosing ILD, data are available in the broader patient population of chronic fibrosing ILDs. A number of these biomarkers show promise, however, none have been validated. In this review article, we assess both the status of proposed biomarkers for chronic fibrosing lung diseases with a progressive phenotype in predicting disease risk or predisposition, diagnosis, prognosis, and treatment response and provide a direct comparison between IPF and other chronic fibrotic ILDs. We also reflect on the current clinical usefulness and future direction of research for biomarkers in the setting of chronic fibrosing ILDs with a progressive phenotype.