Priya Balakrishnan, MD, MS, FCCP

ILDs often require pharmacological therapy to prevent progressive loss of lung function. The initial treatment choice is determined by the ILD subtype.¹ Telomeres shorten with cellular replication and the natural aging process, and telomere dysfunction has been linked with ILD development and disease progression.¹ A pharmacogenomic relationship may exist between immunosuppressive treatment and shorter leukocyte telomeres. Historical use of immunosuppression is associated with worse survival for patients with IPF with short age-adjusted telomere length.¹ Genetic factors may contribute to ILD development, as seen in familial interstitial pneumonia (FIP).² More than 10 gene mutations are associated with FIP.² When FIP is suspected, next-generation sequencing (NGS) helps facilitate a targeted gene panel with a known familial ILD association. Initial studies of familial clustering of ILD led to the discovery of gene mutations implicated in telomere homeostasis (telomere-related genes) and surfactant homeostasis (surfactant-related genes).² The disease phenotype in families was not limited to IPF, but included various fibrosing diseases, all of which have the potential for progressive pulmonary fibrosis. Genetic and epigenetic (eg, viral, exposure) underpinnings highlight the complexity of ILD etiology, with mutations in telomere-related and surfactant-related genes contributing to pulmonary fibrosis phenotypes.³ As research advances, understanding these genetic, environmental, and molecular mechanisms holds promise for tailored therapeutic strategies for ILD management.