Prognostic impact of single moderate exacerbation in COPD patients: Analysis of 12-year mortality and future exacerbation risk.

Abstract

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 strategy lowered the threshold for defining high-risk chronic obstructive pulmonary disease (COPD) by classifying patients with a single moderate exacerbation as high risk (Group E). Evidence supporting the prognostic significance of this change remains limited. Does one moderate exacerbation identify patients at increased risk of future exacerbations and long-term mortality, and does the GOLD 2026 exacerbation-based risk definition improve prognostic performance compared to GOLD 2025? We analyzed data from the Korean COPD Subgroup Study, a prospective multicenter COPD cohort. Patients were classified by exacerbation history during the first year as no exacerbation, one moderate exacerbation, or ≥ 2 moderate or ≥ 1 severe exacerbations. Future exacerbations during the second year were evaluated using negative binomial regression. Twelve-year all-cause and respiratory mortality were assessed using Cox proportional hazards models. The prognostic performance of GOLD 2025 and GOLD 2026 exacerbation-based risk definitions was compared using time-dependent area under the curve analysis. Among 1,551 patients, 241 (15.5%) experienced one moderate exacerbation and 392 (25.3%) experienced frequent or severe exacerbations. Compared with no exacerbations, one moderate exacerbation was associated with higher risks of future moderate-to-severe exacerbations (aIRR, 2.42; 95% CI, 1.85-3.17) and severe exacerbations (aIRR, 2.21; 95% CI, 1.27-3.85). Over long-term follow-up of up to 12 years, one moderate exacerbation was independently associated with increased all-cause mortality (aHR, 1.49; 95% CI, 1.02-2.15) and respiratory mortality (aHR, 3.21; 95% CI, 1.76-5.88). The GOLD 2026 definition showed better 10-year discrimination for all-cause mortality than the GOLD 2025 definition (AUC, 0.760 vs 0.734; ΔAUC, 0.025; 95% CI, 0.004-0.046). A single moderate exacerbation identifies patients at increased risk of future exacerbations and mortality, supporting their classification as high risk under GOLD 2026.