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Prognostic Impact of Single Moderate Exacerbation in Patients With COPD: Analysis of 12-Year Mortality and Future
Joon Young Choi1, Hyoung Kyu Yoon2, Ji-Yong Moon3
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Background:
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 strategy lowered the threshold for defining high-risk COPD by classifying patients with a single moderate exacerbation as high risk (group E). Evidence supporting the prognostic significance of this change remains limited.
Research Question:
Does 1 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 with GOLD 2025?
Study Design And Methods:
We analyzed data from the Korean COPD Subgroup Study (KOCOSS), a prospective multicenter COPD cohort. Patients were classified by exacerbation history during the first year as no exacerbation, 1 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.
Results:
Among 1,551 patients, 241 (15.5%) experienced 1 moderate exacerbation, and 392 (25.3%) experienced frequent or severe exacerbations. Compared with no exacerbations, 1 moderate exacerbation was associated with higher risks of future moderate-to-severe exacerbations (adjusted incidence rate ratio, 2.42; 95% CI, 1.85-3.17) and severe exacerbations (adjusted incidence rate ratio, 2.21; 95% CI, 1.27-3.85). Over long-term follow-up of up to 12 years, 1 moderate exacerbation was independently associated with increased all-cause mortality (adjusted hazard ratio, 1.49; 95% CI, 1.02-2.15) and respiratory mortality (adjusted hazard ratio, 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 (area under the receiver operating characteristic curve, 0.760 vs 0.734; Δ area under the receiver operating characteristic curve, 0.025; 95% CI, 0.004-0.046).
Interpretation:
Our results show that a single moderate exacerbation identifies patients at increased risk of future exacerbations and mortality, supporting their classification as high risk under GOLD 2026.
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