Exosomes from activated neutrophils had considerably higher quantities of surface NE compared to quiescent exosomes. Exosomal NE was resistant toinhibition by α1AT. Activated, but not quiescent, exosomesdestroyed the collagen fibrils over time.When exosomes were administered intratracheallyinto A/J mouse airways, activated but not quiescent neutrophil exosomes caused the hallmarks of COPD, alveolar enlargement,increased airway resistance, and RVH, compared to mice treated with PBS. Human COPD lung-derived CD63+/CD66b+ exosomes induced marked alveolar enlargement and RVH. This evidence concerns the gene CEACAM8 and chronic obstructive pulmonary disease.