Sputum Eosinophilia and Magnetic Resonance Imaging Ventilation Heterogeneity in Severe Asthma

Rationale: Inflammation and smooth muscle dysfunction are integral components of severe asthma that contribute to luminal obstruction causing airflow limitation, ventilation heterogeneity, and symptoms. This is important for guiding treatment decisions directed at the inflammatory (e.g., anti-T-helper cell type 2 monoclonal antibodies) and noninflammatory, smooth muscle-mediated (e.g., bronchial thermoplasty) components of severe asthma. Objectives: To investigate the contribution of eosinophilic bronchitis and smooth muscle dysfunction to magnetic resonance imaging (MRI) ventilation heterogeneity in patients with severe asthma. Methods: We measured the inhaled hyperpolarized gas MRI response to salbutamol as a marker of smooth muscle dysfunction, and sputum eosinophils as a marker of airway inflammation, and their contributions to ventilation heterogeneity (quantified as the ventilation defect percent [VDP]) in 27 patients with severe asthma. Spirometry and forced oscillation airway resistance measurements were also acquired pre- and postsalbutamol. Patients were dichotomized on the basis of sputum eosinophilia, and pre- and postsalbutamol VDP and physiological measurements were evaluated. Measurements and Main Results: MRI VDP improved with salbutamol inhalation in patients in whom sputum eosinophilia was uncontrolled (>= 3%, n = 16) (P = 0.002) and in those in whom it was controlled (<3%, n = 11) (P = 0.02), independent of improvements in FEV1, indicating smooth muscle response. In those patients in whom sputum eosinophilia was uncontrolled, greater VDP persisted postsalbutamol (P = 0.004). Postsalbutamol VDP correlated with sputum eosinophils (r = 0.63; P = 0.005). Conclusions: In patients with severe asthma, MRI regionally identifies the inflammatory and noninflammatory components of airway disease. Ventilation heterogeneity persists postsalbutamol in patients with uncontrolled eosinophilic bronchitis, which may be the functional consequence of airway inflammation.