Reduced treatment response to inhaled corticosteroids in current smokers with COPD, regardless of blood eosinophil count: insights from the FLAME trial

Inhaled corticosteroids (ICSs) benefit patients with chronic obstructive pulmonary disease at high risk of exacerbations with raised blood eosinophil count (BEC). Emerging evidence suggests current smokers show a reduced response to ICS. This post-hoc analysis of the FLAME trial explored the impact of smoking status on the efficacy of long-acting beta-2 agonist (LABA)+ICS versus LABA+long-acting muscarinic antagonist (LAMA) for preventing exacerbations. Our findings indicate that LABA+LAMA is superior to LABA+ICS in preventing moderate to severe exacerbations in current smokers and inferior in ex-smokers with BEC ≥200 cells/µL. Smoking status significantly modifies ICS treatment effects on exacerbation outcomes, suggesting reduced ICS efficacy in current smokers, regardless of BEC.