Genomic Profiling for Predictive Treatment Strategies in Fibrotic Interstitial Lung Disease

Abstract

Idiopathic pulmonary fibrosis (IPF) has traditionally been considered the archetype of progressive fibrotic interstitial lung diseases (f-ILDs), but several other f-ILDs can also manifest a progressive phenotype. Integrating genomic signatures into clinical practice for f-ILD patients may help to identify patients predisposed to a progressive phenotype. In addition to the risk of progressive pulmonary fibrosis, there is a growing body of literature examining how pharmacogenomics influences treatment response, particularly regarding the efficacy and safety profiles of antifibrotic and immunomodulatory agents. In this narrative review, we discuss current studies in IPF and other forms of pulmonary fibrosis, including systemic autoimmune disorders associated ILDs, sarcoidosis and hypersensitivity pneumonitis. We also provide insights into the future direction of research in this complex field.

Keywords: antifibrotics; idiopathic pulmonary fibrosis; interstitial lung diseases; nintedanib; pharmacogenomics; pirfenidone; precision medicine.

Figure 1

Pharmacogenomic implications of single nucleotide polymorphisms (SNPs) within the main genes involved in IPF. SNPs and specific genotypes in TERT, TOLLIP, MUC5B, Desmoplakin and TGF-β1 are associated with different responses to antifibrotics, muco-regulatory/antioxidant therapies and/or increased susceptibility to adverse events after lung transplantation. Chr: Chromosome; FVC: Forced vital capacity; GVHD: Graft-versus-host disease; IPF: Idiopathic pulmonary fibrosis; MUC5B: Mucin-5B; NAC: N-Acetylcysteine; TERT: Telomerase reverse transcriptase; TGF-β1: transforming growth factor beta 1; TOLLIP: Toll-interacting protein; ↑: increased; ↓: decreased.