Table 3.
Comparative metabolic reprogramming of macrophages in chronic lung diseases.
| Feature | Asthma | COPD | IPF |
|---|---|---|---|
| Dominant phenotype | M2-like, but dysfunctional in severe disease | Mixed M1/M2, functionally impaired | Hypermetabolic, profibrotic |
| Primary metabolic shift | ↑ FAO, ↑ arginase activity, altered lipid mediator metabolism | Mitochondrial dysfunction → ↑ glycolysis (pseudo-hypoxia), ↓ OXPHOS | ↑ Glycolysis + ↑ FAO (hybrid state) |
| ROS/RNS balance | ↑ ROS, impaired antioxidant defenses | Excessive ROS + peroxynitrite (ONOO-) due to iNOS/Arg1 co-expression | ↑ ROS + RNS, mitochondrial and NADPH oxidase-derived |
| Iron metabolism | Mild changes, not central | Iron overload, siderophages, Fenton reaction | Iron overload, CD71low AMs, ferroptosis link |
| Regulatory metabolites | Imbalanced lipid mediators (↓PGE2, ↓ resolvins, ↑ leukotrienes) | ↓ Glutathione synthesis, impaired antioxidant capacity | ↓ Itaconate (ACOD1), loss of anti-inflammatory brake |
| Crosstalk with other cells | Eosinophils (impaired efferocytosis), epithelial cells | Neutrophils, T cells, epithelial damage | Fibroblasts/myofibroblasts (profibrotic loop) |
| Clinical implication | Contributes to airway remodeling, persistent inflammation | Drives impaired host defense, steroid resistance, emphysema | Sustains fibroblast activation, irreversible fibrosis |