Rethinking GOLD E: The Significance of a Single Moderate Exacerbation in COPD.

The new GOLD 2026 classification includes, for the first time, patients who experience one moderate exacerbation in a year in the E category. This change may have substantial implications, as patients with one moderate exacerbation are more frequent than those with two or more moderate exacerbations or at least one severe exacerbation considered together, according to population-based studies. This reclassification implies that patients with one moderate exacerbation and elevated blood eosinophil counts may initiate triple therapy, and, by being classified as GOLD E, may become candidates for second-line preventive treatments, despite GOLD recommendations for escalation only after two or more moderate exacerbations or one severe exacerbation. The rationale for classifying patients with one moderate exacerbation as GOLD E should rely on evidence of the clinical impact of a single moderate exacerbation and the associated increased risk of poor outcomes. This review summarises evidence from large trials and epidemiological studies regarding these aspects and proposes a pragmatic approach to management for patients with one moderate exacerbation. In conclusion, the impact of a single moderate exacerbation is limited at a population level and although the risk of future exacerbations is higher than in patients with none, it remains low, usually below 50%. Decisions regarding escalation or initiation of preventive therapy in COPD should be individualised, considering additional risk factors such as age, symptom burden, lung function impairment, and comorbidities, as well as patient preferences and values.