Treatment responses to different inhalation therapies in GOLD 2026 group E patients with chronic obstructive pulmonary disease: a stratified analysis

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 report revised the combined chronic obstructive pulmonary disease (COPD) assessment. Patients with one or more exacerbations in the past year are classified into group E, and long-acting β 2 -agonist (LABA) + long-acting muscarinic antagonist (LAMA) + or LABA + LAMA + inhaled corticosteroid (ICS) is recommended as initial inhalation therapy. However, COPD is a heterogeneous disease, and relying solely on exacerbation history may not capture its complexity. Therefore, the purpose of this study was to evaluate the treatment responses to different inhalation therapies in group E patients after stratified analysis based on the forced expiratory volume in the first second percentage of predicted (FEV1%pred), COPD Assessment Test (CAT), and exacerbations in the past year. This was a retrospective cohort study. Patients with COPD in group E (≥1 moderate/severe exacerbation) registered in the RealDTC study between January 2017 and June 2023 were enrolled. Patients were classified into FEV1%pred < 50% and FEV1%pred ≥ 50% groups, CAT < 10 and CAT ≥ 10 scores groups, non-frequent exacerbators and frequent exacerbators groups. Subsequently, all groups were subdivided into four groups: LAMA, LABA + ICS, LABA + LAMA, and LABA + LAMA + ICS. The number of future exacerbations, frequent exacerbations and hospitalizations, and all-cause mortality were collected during one year of follow-up. A total of 3911 patients were enrolled. During one year of follow-up, there were no significant differences in future exacerbations, frequent exacerbations and hospitalizations, and all-cause mortality among LAMA, LABA + LAMA, LABA + ICS, and LABA + LAMA + ICS in the FEV1%pred ≥ 50%, CAT < 10 scores, and non-frequent exacerbators groups. However, patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of future exacerbations and frequent exacerbations than patients treated with LAMA or LABA + ICS in the FEV1%pred < 50%, CAT ≥ 10 scores, and frequent exacerbators groups ( P < 0.05). Although the GOLD 2026 report uniformly recommends LABA + LAMA or LABA + LAMA + ICS as initial inhaled regimens for group E patients, our stratified real-world findings partially diverge from this unified recommendation. Further individualized stratification based on FEV1%pred, CAT scores, and exacerbations in the past year may be beneficial to optimize initial inhalation therapy selection for heterogeneous group E patients.