Introduction: Some patients exhibit characteristics of both asthma and COPD (asthma-COPD overlap [ACO]). There is no gold standard for diagnosing ACO, and limited prospective data exist on the medium-term outcomes of these patients based on the Global Initiative for Asthma (GINA) definition compared to those with asthma or COPD alone. This study assessed the clinical characteristics and risk factors for acute exacerbations (AEs) in ACO patients versus those with COPD or asthma over 3 years.
Methods: Subjects aged over 40 years with a history of asthma and COPD, diagnosed by GINA and Global Obstructive Lung Disease (GOLD) guidelines, were recruited and followed for 3 years. Baseline assessments included a clinical history, symptoms, lung function, a 6-minute walk test (6MWT), blood eosinophil levels, and immunoglobulin E levels. ACO patients were identified per GINA 2017 criteria. AEs were recorded, and risk factors were assessed using Cox regression.
Results: Of 538 patients (299 asthma, 239 COPD), 78 (14.5%) were classified as ACO. Post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted (mean ± SD) was 83.1 ± 19.0% for asthma, 48.0 ± 19.0% for COPD, and 63.0 ± 22.2% for ACO (p < 0.001). Over 3 years, all AEs occurred in 59/272 (21.7%) asthma, 90/188 (47.9%) COPD, and 28/78 (35.9%) ACO patients, while severe AEs requiring hospitalization occurred in 24/272 (8.8%), 79/188 (42.0%), and 20/78 (25.6%), respectively. Compared to asthma patients, ACO patients had a significantly higher risk of first severe AE requiring hospitalization (p < 0.0001) but a lower risk compared to COPD patients (p = 0.014). Risk factors for AEs (all or severe) were: for asthma, prior AE history, shorter 6MWT distance, and lower lung function; for COPD, prior AE history, lower lung function, higher eosinophil count, and being underweight; for ACO, prior AE history and lower lung function.
Conclusion: In this 3-year prospective study using the GINA definition, ACO patients showed an intermediate risk of severe AEs requiring hospitalization compared to asthma (higher) and COPD (lower), with prior exacerbation history and lower lung function as common risk factors across groups.
Trial registration: gov registration number NCT03272932 (registration date: 9 Jan 2017).
Supplementary Information: The online version contains supplementary material available at 10.1186/s12931-026-03643-0.
Keywords: Asthma; COPD; Exacerbations; Overlap.