Molecular Mechanisms Linking Eosinophils to Lung Function Impairment in Respiratory Diseases

Eosinophils are key immunopathological cells in respiratory diseases and contribute to airway inflammation, tissue remodeling, and disease heterogeneity. Although eosinophils have traditionally been regarded as biomarkers of type 2 inflammation, increasing evidence indicates that they also function as active mediators of lung function impairment in selected respiratory diseases, including chronic obstructive pulmonary disease, asthma, and eosinophilic pneumonia. These disorders were selected because they represent distinct yet complementary models of eosinophil-associated airway and parenchymal injury, allowing comparison of shared and disease-specific mechanisms. Mechanistically, eosinophils impair lung function through the coordinated release of cytotoxic granule proteins, reactive oxygen species, lipid mediators, and cytokines, while interacting with epithelial, immune, and structural cells to amplify inflammation, airway remodeling, and tissue injury. These advances have improved understanding of eosinophil biology and facilitated the development of clinically relevant biomarkers and targeted therapies. Blood and sputum eosinophil counts remain the most widely used biomarkers, whereas emerging biomarkers, including eosinophil-derived neurotoxin, may further improve disease stratification and treatment monitoring. Biologics targeting interleukin-5 and its receptor have demonstrated therapeutic benefit in selected eosinophilic respiratory diseases, although treatment responses differ among disease phenotypes. This review summarizes current evidence regarding the molecular mechanisms linking eosinophils to lung function impairment, discusses the evolving role of eosinophils as both biomarkers and pathogenic drivers, and highlights the biomarker and therapeutic implications for precision management of respiratory diseases.