Airway mucus and 129Xe MRI ventilation after single inhaler triple therapy in asthma.

Background: In asthma, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) was previously demonstrated to improve forced expiratory volume in 1 s (FEV1) and asthma control, but the mechanism by which this occurs, especially at the level of the small airways, is not well-understood. We asked the question, does FF/UMEC/VI influence asthma control by improving airway structure-function and airway occlusions? Hence, our objective was to measure airway structure-function using 129Xe magnetic resonance imaging (MRI) ventilation defect percentage (VDP), computed tomography (CT) and airwave oscillometry after 6-week single-inhaler FF/UMEC/VI and 1 year later. Methods: Participants with Global Initiative for Asthma Step 4-5 (GINA4-5) asthma who were poorly controlled on inhaled corticosteroid/long-acting β-2 agonist (ICS/LABA) provided written informed consent to baseline, 6- and 12-week visits as well as an open-extension 1-year visit. All received FF/UMEC/VI (200/62.5/25 µg) at baseline and underwent MRI, spirometry, plethysmography and oscillometry, pre- and post-bronchodilator (BD). The Asthma Control Questionnaire, the Asthma Quality of Life Questionnaire (AQLQ) and St. George's Respiratory Questionnaire (SGRQ) were completed. CT was acquired at baseline and 1 year later. Results: Thirty-one participants (24 females, 54±15 yrs) completed the baseline visit, 28 (21 females, 54±15 yrs) completed the 6-week visit and 15 patients attended the 1-year visit. At 6-weeks, there was significantly improved pre-BD VDP (p=0.02), FEV1 (p=0.008), distal airways resistance (R5-19) (p=0.001), AQLQ (p<0.001) and SGRQ-scores (p=0.001), which persisted at 1 year. VDP improved in participants with elevated mucus score and eosinophil count, while R5-19 improvements were independent of type 2 inflammation. Mean airway mucus score, lumen area and total airway count were significantly improved at 1 year. Conclusions: In participants with GINA4-5 asthma, who had been poorly controlled on ICS/LABA, single-inhaler FF/UMEC/VI resulted in improved VDP and FEV1 at 6-weeks. These improvements persisted 1-year later when airway markers were also significantly improved, consistent with the reversal of airway remodelling.