In this study, we show that the necroptosis markers phosphorylated MLKL (p-MLKL) and high mobility group box 1 (HMGB1) release are markedly elevated in patients with COPD, smoking-exposed mice, and cigarette smoking extract–treated (CSE-treated) lung epithelial cells. The gene discussed is HMGB1; the disease is chronic obstructive pulmonary disease.