Pascoe S, Barnes N, Brusselle G, et al. - In view of the finding that exacerbations of chronic obstructive pulmonary disease (COPD) were significantly reduced with once-daily single-inhaler triple therapy vs dual therapies in the IMPACT trial, and critical modifiers of treatment response to inhaled corticosteroids (ICS) could be blood eosinophil counts and smoking status, researchers intended to model these links and their interactions, including outcomes other than exacerbations. Participants had moderate-to-very-severe COPD and at least one moderate or severe exacerbation in the past year. Comparison between once-daily single-inhaler triple therapy (fluticasone furoate–umeclidinium–vilanterol) vs dual inhaled therapy (fluticasone furoate–vilanterol or umeclidinium–vilanterol) was performed in IMPACT, which was a phase 3, randomised, double-blind, parallel-group, 52-week global research. For regimens including ICS (fluticasone furoate–umeclidinium–vilanterol n = 4,151 and fluticasone furoate–vilanterol n = 4,134) vs a non-ICS dual long-acting bronchodilator (umeclidinium–vilanterol n = 2,070), the magnitude of benefit in attenuating rates of moderate and severe exacerbations was found to rise in proportion with blood eosinophil count. At blood eosinophil count less than 90 cells per μL and at counts of 310 cells per μL or more, the estimated moderate and severe exacerbation rate ratio for triple therapy vs umeclidinium–vilanterol was 0·88 and 0·56, respectively; the corresponding values for fluticasone furoate–vilanterol vs umeclidinium–vilanterol was 1·09 and 0·56, respectively. Compared with current smokers, the corticosteroid response was more at any eosinophil count in former smokers. Overall, findings highlighted the potential of blood eosinophil count and smoking status evaluation to optimize ICS use in clinical practice in patients with COPD and a history of exacerbations.