COPD

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation that is not fully reversible, resulting from chronic inflammatory responses to noxious particles and gases, predominantly cigarette smoke. At the cellular level, COPD pathogenesis involves two interconnected processes: small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema). Cigarette smoke activates alveolar macrophages and epithelial cells, releasing chemotactic factors (IL-8, LTB4, TNF-α) that recruit neutrophils and CD8+ cytotoxic T lymphocytes. Neutrophil-derived serine proteases (neutrophil elastase, proteinase 3, cathepsin G) and matrix metalloproteinases (MMP-9, MMP-12) degrade elastin and collagen in the alveolar walls, overwhelming antiprotease defenses (α1-antitrypsin, tissue inhibitors of metalloproteinases). This protease-antiprotease imbalance is the central mechanism of emphysematous destruction. Oxidative stress from cigarette smoke and activated inflammatory cells generates reactive oxygen species that inactivate α1-antitrypsin (methionine oxidation), impair mucociliary clearance, and activate NF-κB pro-inflammatory signaling. In the small airways, chronic inflammation causes goblet cell metaplasia, mucus hypersecretion, peribronchiolar fibrosis, and smooth muscle hypertrophy, leading to progressive narrowing. Emphysema destroys alveolar attachments (tethering) that normally hold small airways open during expiration, contributing to dynamic airway collapse and air trapping. The...