# The role of programmed cell death in chronic obstructive pulmonary disease: from pathogenesis to treatment

## TL;DR

This review explores how programmed cell death contributes to COPD, linking it to immune dysfunction and offering new treatment strategies.

## Contribution

The paper introduces a novel immunological framework connecting programmed cell death mechanisms to COPD pathogenesis and treatment.

## Key findings

- Programmed cell death types like apoptosis and pyroptosis play key roles in COPD-related immune responses and tissue damage.
- PCD mechanisms bridge innate and adaptive immune dysfunction in COPD through DAMPs release and inflammasome activation.
- Targeting PCD pathways offers potential new therapeutic strategies for COPD treatment.

## Abstract

Chronic obstructive pulmonary disease (COPD) is a complex chronic disease characterized by persistent respiratory symptoms and irreversible airflow limitation, and has become a significant global public health issue. Its pathogenesis is highly complex, involving airway inflammation, immune imbalance, oxidative stress, and multiple abnormalities at the cellular and molecular levels. Immunologically, COPD represents a chronic state of “immune homeostasis imbalance” and “immune surveillance failure,” coexisting with persistent activation of innate immunity and dysfunction of adaptive immunity. In recent years, research on programmed cell death (PCD) has gradually gained attention. Especially in the development of COPD, various forms of PCD, including apoptosis, necroptosis, pyroptosis, and ferroptosis, have shown significant biological significance in airway epithelial injury, immune response regulation, and tissue remodeling. This review proposes a core immunological proposition: PCD serves as a key “bridge,” amplifying the innate immune response through mechanisms such as DAMPs release, NLRP3 inflammasome, and immunogenic cell death on one hand, while driving adaptive immune disorders in COPD by affecting antigen presentation, Th1/Th2/Th17 imbalance, T cell exhaustion, and “autoimmune-like” responses on the other hand. This article reviews the roles and molecular mechanisms of various PCDs (apoptosis, necroptosis, ferroptosis, pyroptosis, and copper death) in COPD. It also discusses the associations between different types of PCD, as well as the signaling pathways and regulatory mechanisms of PCD, integrating existing evidence within immunological frameworks such as “immunogenic vs. immunosuppressive cell death,” “defective efferocytosis,” and “Th1/Th2/Th17 imbalance and immunometabolism.” By integrating the latest research findings, it provides a new strategy for targeting PCD in the treatment of COPD. This article aims to provide a deeper immunological understanding of the pathological mechanisms of COPD and to offer new ideas and directions for future therapeutic targets and strategies.