Abstract Rationale Blood eosinophil (EOS) count has emerged as a key biomarker for endophenotyping and guiding treatment in Chronic Obstructive Pulmonary Disease (COPD). However, studies have reported contrasting findings regarding the relationship between eosinophil thresholds and clinical outcomes. We aimed to evaluate the clinical characteristics and outcomes of COPD patients stratified by peripheral blood EOS levels. Methods Stable COPD patients attending Singapore General Hospital COPD clinic were recruited from 2013 to 2025. Clinical data including baseline blood EOS level were collected at enrollment. Patients were stratified into three groups based on their blood EOS count: Group 1 (0.15 ×109/L, n = 180), Group 2 (0.15-0.3 ×109/L, n = 118), and Group 3 (0.3 ×109/L, n = 139). Data on demographics, symptom scores, lung function, exacerbation history, and medication use were compared across the groups. Mortality outcomes were assessed through October 2025. Results A total of 437 patients with baseline EOS data were included. The cohort was predominantly male (96%), with a median age of 71 years (IQR 65-77) and median FEV1 of 53% predicted (IQR 40-65). The median follow-up duration were 1770 days. Group 1 was associated with a higher proportion of frequent exacerbators (53.9%, p = 0.0032), hospitalized exacerbations (51.1%, p = 0.0092), and poorer lung function (Post-BD FEV1 % predicted, median 48.50, p = 0.0111) at baseline. In contrast, Group 3 had a higher symptoms burden (median CAT score 13.5, p = 0.029). Both Group 1 and 3 had the highest proportion of patients receiving inhaled corticosteroid containing therapy (Group 1: 48.9%, Group 2: 35.6%, Group 3: 48.2%, p = 0.05). Kaplan-Meir analysis showed significant survival differences among groups with Group 1 having the highest mortality (log-rank p = 0.05). Conclusion COPD with low EOS (0.15 ×109/L) is a distinct subgroup with worse clinical outcomes. As current biologic therapies are indicated for subgroup with high EOS, patients with low eosinophils represent an important group with unmet therapeutic needs. This abstract is funded by: Chongqing Science and Health Joint Medical Research Project (2024GGXM001, 2023QNXM045), Chongqing Natural Science Foundation General Program (CSTB2024NSCQ-MSX1114) and the Clinical Research Special Project of the Second Affiliated Hospital of Army Medical University (2024F030).
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