A recent study in eBioMedicine reported findings on features associated with asthma-COPD overlap (ACO) in over 2,400 smokers. Patients with ACO showed the greatest symptom burden, severe impairments in lung function, and distinctive inflammatory profiles compared to patients with asthma or COPD alone. The structural and molecular characteristics of ACO, including airway remodeling and hypoxia-driven metabolic adaptations, were highlighted. The research aimed to guide targeted therapeutic strategies for this patient population.