HMOX1 and chronic obstructive pulmonary disease: Local oxidative stress (CS/hypoxia) directly induces upregulation of HO-1 expression in brain tissue; (2) continuous delivery of lung-derived Exos combined with COPD pathological modification prolongs the retention time of brain Exos, causing the total level of HO-1 in the brain to exceed the toxicity threshold; and (3) free Fe2+ produced by HO-1 catalysis induces ferroptosis.