Cytoplasmic accumulation of HMGB1: Cytoplasmic accumulation of HMGB1 in secretory lysosomes is a pathogenic feature of COPD, cigarette smoke extract (CSE), and ventilator-induced lung injury [16,17,18] and is a prerequisite for extracellular HMGB1 release. Here, HMGB1 is linked to chronic obstructive pulmonary disease.