Visualizing Improvements in Airway Dysfunction After Inhaled Therapy in Patients With Uncontrolled Asthma: A Narrative Review

Clinical trials investigating asthma therapies typically rely on pulmonary function tests including spirometry markers, such as forced expiratory volume in 1 s, to evaluate efficacy. While these measures provide insights into the action of bronchodilators on global lung function, their specific effects on the airways and the relationship between clinical improvements and airway dysfunction remains poorly understood. In recent years, pulmonary functional imaging methods, such as hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI), have enabled the analysis of airway dysfunction in patients with asthma utilizing ventilation defect percent (VDP). In this narrative review, we summarize clinical evidence about the impact of inhaled bronchodilator therapies on airway dysfunction in patients with asthma, focusing on studies that utilized ¹²⁹Xe MRI to visualize and quantify MRI VDP. ¹²⁹Xe MRI VDP has been shown to be a well-tolerated and sensitive technique for enabling the visualization and quantification of airway functional changes over time in patients with asthma. This has been shown not only in a controlled clinical trial environment but also in a real-world setting, in patients with both controlled and poorly controlled asthma. A recent study evaluating single-inhaler triple therapy in patients with uncontrolled moderate-severe asthma, despite inhaled corticosteroid/long-acting β₂-agonist maintenance therapy, demonstrated that daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI 200/62.5/25 µg) led to significantly improved ¹²⁹Xe MRI VDP after only 6 weeks, which was in line with broader central/distal airway function and quality of life improvements. These results highlight the capacity of ¹²⁹Xe MRI VDP to detect early responses to treatment. In addition, the mechanistic insights provided by ¹²⁹Xe MRI VDP also indicated that these benefits are likely due to the combination of UMEC (a long-acting muscarinic antagonist) and an efficacious inhaled corticosteroid, addressing undertreated inflammatory bronchoconstriction, helping to restore airway caliber and function that more closely resemble the airways of a healthy individual.Videos available for this article.