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Conclusion Our current data from multiple models, including PBECs, HBECs, SD rats as well as Nrf2/ mice reveal the preventive effects of AZI on CSE-induced airway epithelial barrier dysfunction in COPD and underscore the importance of Nrf2/GCL/GSH antioxidant signaling pathway as the regulatory target of macrolides in the protection of airway epithelial barrier