Chronic obstructive pulmonary disease (COPD) causes extensive changes in the gene expression of the lungs, reprogramming them to function like an immune organ.[1] Research has shown that COPD activates genes associated with trained immunity, which is the ability of innate immune cells (macrophages, monocytes, and NK cells) to respond more quickly and intensely to infections.[2] The disease also promotes tissue damage by activating multiple types of regulated cell death, including apoptosis, necroptosis, and ferroptosis.[1] COPD disrupts the normal identity of up to 10 of the 14 major lung cell types and causes their pathological transformation with aberrant expression of more than 50 cell-specific genes.[1] Alveolar macrophages show dysregulation of immune checkpoints, with reduced expression of PVR protein (CD155) observed in severe emphysema.[1] The disease also weakens the suppressive capacity of regulatory T cells, which normally dampen inflammation, through the downregulation of key immunosuppressive genes.[1] These findings suggest that COPD fundamentally alters immune signals in the lung and create new opportunities for immunomodulatory therapy.