NFE2L2 and chronic obstructive pulmonary disease: Complementary animal experiments demonstrate that treadmill exercise increases muscle-derived mediators (for example, irisin), upregulates pulmonary Nrf2 and HO-1 expression, and mitigates CS–induced emphysematous changes, thereby providing tissue-level evidence that exercise engages Nrf2-centered antioxidant pathways relevant to COPD protection [147].