Bronchial thermoplasty reduces ventilation heterogeneity measured by phase-resolved functional lung magnetic resonance imaging in severe asthma

Rationale: Bronchial thermoplasty (BT) is a treatment option for patients with severe asthma. Despite demonstrated sustained symptomatic benefits, its mechanism of action remains unclear, with emerging evidence suggesting a reduction in ventilation heterogeneity. Objective: This study aims to determine if BT reduces ventilation heterogeneity as measured by phase-resolved function lung magnetic resonance imaging (PREFUL MRI). Methods: Twenty-one patients with severe asthma and 14 healthy volunteers (HV) were recruited. Patients were assessed at baseline and 6-months after BT. Data collected included asthma control questionnaire (ACQ-5), exacerbation frequency, and short-acting beta-agonist (SABA) and oral corticosteroid (OCS) use. Both HV and patients also underwent lung function tests and PREFUL MRI. Ventilation heterogeneity was assessed using ventilation defect percentage (VDP) of static regional ventilation (RVent) and dynamic flow-volume loop cross-correlation metric (FVL-CM), and interquartile distance (IQD) of the ventilation distribution. Results: At baseline, patients had a significantly higher RVent VDP (20.0 ± 14.5 vs 3.8 ± 2.2%, p < 0.001), FVL-CM VDP (23.7 ± 17.8 vs 2.4 ± 2.3%, p < 0.001), and IQD (0.61 ± 0.27 vs 0.32 ± 0.05, p < 0.001) than HV. Post BT, significant reductions in RVent VDP (15.5 ± 11.7 vs 20.0 ± 14.5%, p < 0.001), FVL-CM VDP (18.7 ± 13.9 vs 23.7 ± 17.8%, p < 0.001), and IQD (0.53 ± 0.22 vs 0.61 ± 0.27, p < 0.001) were observed in patients, along with significant improvements in ACQ-5, exacerbation frequency, SABA and OCS use. No change in lung function was seen. Significant correlations were observed between ΔACQ and ΔRVent VDP (ρ = 0.50, p = 0.02), ΔFVL-CM VDP (ρ = 0.51, p = 0.02), and ΔIQD (ρ = 0.45, p = 0.04). Conclusions: Clinical benefits post BT are accompanied by a reduction in ventilation heterogeneity that are undetected by lung function test. These findings provide valuable insights into the mechanisms of action of BT and highlight the complementary role of functional lung imaging in the study of pulmonary diseases for which traditional lung function tests may be insensitive at detecting therapeutic response.