Objective: To explore the efficacy of Seretide and Breztri Aerosphere inhalation in the treatment of patients with asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS). Methods: A total of 103 patients with ACOS were selected as study subjects and divided into the Seretide group (n = 52) and the Breztri Aerosphere group (n = 51) according to different treatment regimens. Patients in the Seretide group were treated with Seretide, while those in the Breztri Aerosphere group received Breztri Aerosphere treatment. The treatment course lasted 90 days. Clinical efficacy, disease control status [Chronic Obstructive Pulmonary Disease Assessment Test (CAT) score, Asthma Control Test (ACT) score], improvement in lung function [forced expiratory volume in one second (FEV?), forced vital capacity (FVC), inspiratory capacity to total lung capacity ratio (IC/TLC)], immune changes in T lymphocytes [T helper 17 cells (Th17), regulatory T cells (Treg)], serum indicators [interleukin-17 (IL-17), eosinophil count (EOS)], incidence of adverse reactions, and disease progression were compared between the two groups. Results: The clinical efficacy in the Breztri Aerosphere group was significantly better than that in the Seretide group (P 0.05). However, the acute exacerbation rate and emergency visit rate in the Breztri Aerosphere group were significantly lower than those in the Seretide group (P < 0.05). Conclusion: Breztri Aerosphere can effectively improve pulmonary function and immune regulation in patients with ACOS, with a favorable safety profile. It is worthy of clinical promotion and application.