Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease whose progression is orchestrated by tissue macrophages. Their functions are regulated by two opposing lipid pathways that initiate inflammation or induce tissue regeneration. In COPD patients, macrophage lipid signaling is disrupted, resulting in uncontrolled responses and irreversible lung damage. I will use bronchoscopy samples from severe-stage COPD patients to investigate the effects of impaired macrophage lipid signaling. Single-cell transcriptomics combined with quantitative metabolomics and cutting-edge computational analysis will critically assess the role of lipid signaling in macrophage immunity and test whether certain lipid classes may represent therapeutic targets for COPD.