The high-risk B-to-E transitional phenotype: a prospective multi-centre validation of patient reclassification under the updated GOLD 2026 criteria

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 criteria lowered the threshold for classifying Group E to ≥1 moderate or severe acute exacerbation in the last year. However, the scale of patient reclassification and its clinical justification in real-world settings have not been validated. Methods: We utilised a prospective, multi-centre Chinese chronic obstructive pulmonary disease (COPD) cohort (n = 966), and applied the GOLD 2015, 2025, and 2026 criteria to the same cohort, focusing on patients who shifted from group B under GOLD 2025 to group E under GOLD 2026. The primary outcome was time to first moderate-to-severe acute exacerbation; secondary outcomes included symptom burden, health care resource utilisation, and clinical features of patients in the subgroups. Results: Of 952 analysable participants, 242 were classified as shift-to-E. During an average follow-up of 10.3 months, the shift-to-E subgroup showed a 92% higher risk than stable B (hazard ratio (HR) = 1.92; 95% confidence interval (CI) = 1.14-3.23, P = 0.01441). Its adjusted follow-up scores of the COPD assessment test (CAT = 14.83) and the modified Medical Research Council dyspnoea scale (mMRC = 2.191) were comparable to stable E (CAT = 15.30 and mMRC = 2.214) and significantly higher than stable B. The subgroup also had longer baseline hospital stays (12.31 days) than stable B (8.246 days), supporting the utility of the GOLD 2026 for precise COPD stratification. Conclusions: The GOLD 2026 update effectively identifies a substantial subgroup of patients with a distinct high-risk B-E transitional phenotype. Their exacerbation risk and symptom burden approximate those of the traditional high-risk group E, providing direct prognostic evidence for treatment escalation based on a history of just one moderate exacerbation. This supports the clinical utility of the new criteria for precise risk stratification. Registration: Chinese Clinical Trial Registry (ChiCTR-POC-17010431).