BackgroundLimited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment. ObjectiveTo explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting β2-agonist (SABA) usage to determine the clinical relevance of moderate events. MethodsCAPTAIN was a Phase IIIA 24–52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting β2-agonist. Outcomes reportedinclude: first post-randomization exacerbation event by severity (Weeks 1–52), frequency and duration of moderate and severe exacerbations and time course of changes over ±14-day peri-exacerbation period for lung function, symptoms, limitations, and SABA use. ResultsOf the intent-to-treat population (N=2436), 550 patients (23%) continued to 52 weeks. There were 529 moderate and 546 severe exacerbations. Lung function changes were similar, but symptom, physical activity limitation scores, and SABA use were higher, for severe versus moderate exacerbations. Lung function decline preceded increases in symptom, physical activity limitation scores, and SABA use, irrespective of exacerbation severity. Lung function variables, limitation scores, and SABA use returned to pre-exacerbation baseline after ∼8–12 days for both exacerbation severities. ConclusionWhile severe events were associated with greater impact on symptoms, physical activity limitations, and SABA use, onset and time to resolution were generally similar for moderate and severe events. Both exacerbation severities represent clinically important deteriorations comprising clinical and functional changes. NCT02924688.