Most studies have shown that HMGB1 plays a role in immune inflammation in smoking‐related COPD by directly binding to RAGE or TLR4, but HMGB1 may also activate proinflammatory cytokines through other pathways, such as the NFκB and JNK/p38 pathways via MyD88‐mediated pathways and lead to airway inflammation. This evidence concerns the gene TLR4 and chronic obstructive pulmonary disease.