Effects of Anti-T2 Biologic Treatment on Lung Ventilation Evaluated by MRI in Adults With Prednisone-Dependent Asthma

BACKGROUND: The functional consequence of airway obstruction in asthma can be regionally measured using inhaled gas MRI. Ventilation defects visualized by MRI persist post-bronchodilator in patients with severe asthma with uncontrolled sputum eosinophilia and may be due to eosinophil-driven airway pathology that is responsive to "anti-T2" therapy. RESEARCH QUESTION: Do anti-T2 therapies that clear eosinophils from the airway lumen decrease ventilation defects, measured by inhaled gas MRI, in adults with prednisone-dependent asthma? STUDY DESIGN AND METHODS: Inhaled hyperpolarized gas MRI was performed before and after bronchodilation in 10 prednisone-dependent patients with asthma with uncontrolled eosinophilic bronchitis (sputum eosinophils ≥3%) at baseline and 558 (100-995) days later when their eosinophilic bronchitis had been controlled (sputum eosinophils <3%) by additional anti-T2 therapy. The effect of anti-T2 therapy on ventilation defects, quantified as the MRI ventilation-defect-percent (VDP), was evaluated before and after bronchodilation for all patients and compared between patients dichotomized based on the median percentage of sputum eosinophils at baseline (15.8%). RESULTS: MRI VDP was improved pre- (ΔVDP_+anti-T2: -3% ± 4%, P = .02) and post-bronchodilator (ΔVDP_+anti-T2: -3% ± 4%; P = .04) after additional anti-T2 therapy that controlled eosinophilic bronchitis (n = 2 mepolizumab, n = 2 reslizumab, n = 3 benralizumab, n = 1 dupilumab, n = 2 increased daily prednisone). A greater post-bronchodilator ΔVDP_+anti-T2 was observed in those patients with median or higher percentage of sputum eosinophils at baseline (≥15.8%; P = .01). In 7 of 10 patients with asthma, residual ventilation defects persisted despite bronchodilator and anti-T2 therapy. INTERPRETATION: Controlling sputum eosinophilia with anti-T2 therapies improves ventilation defects, measured by inhaled gas MRI, in adults with prednisone-dependent asthma.