Proteomics in interstitial lung disease: new insights into pathogenesis, diagnosis and treatment

Interstitial lung disease (ILD), representing a heterogeneous group of diffuse parenchymal lung disorders, is characterized by inflammation and/or fibrosis within the alveolar interstitium of the lung. The overlapping clinical manifestations and progressive patterns of ILD subtypes pose substantial challenges for accurate diagnosis and effective disease management. In recent years, application of diverse omics approaches in clinical research has yielded promising insights into complex disease pathophysiology. Among the spectrum of omics technologies, proteomics enables comprehensive characterization of dynamic protein alterations, providing a direct snapshot of the functional state of biological system, including disease-specific biomarkers and dysregulated pathways. This review highlights recent proteomic discoveries in idiopathic pulmonary fibrosis (IPF), autoimmune ILDs, exposure-related ILDs, sarcoidosis, and other ILDs, along with emerging therapeutic avenues. The key dysregulated pathways and candidate biomarkers that are critical for differential diagnosis, prognosis, disease monitoring, and treatment response assessment are outlined. Most of the proteomic studies are reported in IPF, given its increasing prevalence and heterogeneous disease progression. In summary, pathogenesis of ILD involves a complex interplay among complement activation, humoral immune responses, and extracellular matrix remodeling, with the dysregulation of key pathway mediators varying across disease stages and subtypes. Large cohort studies following uniform experimental methods across diverse ethnic population are essential for validation of these pathways and mediators to advance disease understanding and develop "true" clinical biomarkers with diagnostic and therapeutic utility.