BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 revised the combined chronic obstructive pulmonary disease (COPD) assessment, merging groups C and D into group E, and revised the initial inhalation therapy recommendation. We aimed to evaluate the treatment responses among different inhalation therapies in GOLD group E patients stratified by the COPD assessment test (CAT) scores and forced expiratory volume in one-second percentage of predicted (FEV1%pred). METHODS: In this retrospective cohort study, we included patients with COPD registered in the Real World Research of Diagnosis and Treatment of COPD (RealDTC) study between January 2017 and June 2023. According to the GOLD 2023 report, we enrolled patients assigned to GOLD group E based on exacerbations in the past year (≥2 exacerbations or ≥1 hospitalisation) in this study. We classified them into the FEV1%pred <
50% and FEV1%pred ≥50% groups, or CAT<
10 and CAT≥10 groups. Subsequently, we divided all groups into four subgroups: long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS. All patients finished one year of follow-up, during which we collected data on exacerbations, frequent exacerbations, hospitalisations, and all-cause mortality. We defined frequent exacerbations as ≥2 exacerbations per year. RESULTS: We enrolled a total of 3173 patients in this study. During one year of follow-up, there were no significant differences in exacerbations, frequent exacerbations, hospitalisations, and all-cause mortality among LAMA, LABA + LAMA, LABA + ICS, and LABA + LAMA + ICS in the FEV1%pred ≥50% and CAT<
10 groups. However, the patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbations and frequent exacerbations compared with the patients treated with LAMA or LABA + ICS in the FEV1%pred <
50% and CAT≥10 groups (P <
0.05). CONCLUSIONS: Patients with COPD in GOLD group E should be further stratified to determine the appropriate initial inhalation therapy. This approach may provide more precise treatment for GOLD group E patients.