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The levels of TUNEL-positive cells, activated Caspase-3/9, and the Bax/Bcl-2 ratio are significantly elevated in the airway epithelium and alveolar epithelial cells of COPD patients ( In vitro models of human bronchial epithelial cells and alveolar epithelial cells treated with cigarette smoke extract (CSE) show upregulation of Fas, FasL, TNF-, and TRAIL expression, accompanied by the activation of initiator Caspase-8, executioner Caspase-3 cleavage, and loss of mitochondrial membrane potential, suggesting a coupling of the typical death receptor pathway with the intrinsic mitochondrial pathway in an extrinsic-mitochondrial amplification manner ( Under physiological conditions, the immunologically silent apoptosis occurring in airway and alveolar epithelium can induce macrophages to produce anti-inflammatory factors such as TGF- and IL-10 through timely efferocytosis, thereby maintaining local tolerance and promoting inflammation resolution