Is Computed Tomography Airway Count Related to Asthma Severity and Airway Structure and Function?

Rationale: In patients with asthma, X-ray computed tomography (CT) has provided evidence of thickened airway walls and airway occlusions, but the total number of CT-visible airways and its relationship with disease severity is unknown. Objectives: To measure CT total airway count (TAC) in asthma and evaluate relationships with asthma severity, airway morphology, pulmonary function, and magnetic resonance imaging (MRI) ventilation. Methods: Participants underwent post-bronchodilator inspiratory CT, and prebronchodilator and post-bronchodilator spirometry and hyperpolarized 3 He MRI. CT TAC was quantified as the sum of airways in the segmented airway tree, and airway wall area percent (WA%) and lumen area were measured. MRI ventilation abnormalities were quantified as the ventilation defect percent. Measurements and Main Results: We evaluated 70 participants, including 15 Global Initiative for Asthma (GINA) steps 1 to 3, 19 GINA 4, and 36 GINA 5 participants with asthma. As compared with GINA 1 to 3, TAC was significantly diminished in GINA 4 ( P  = 0.03) and GINA 5 ( P  = 0.045). Terminal airway intraluminal occlusion was present in 5 (2 GINA 4 and 3 GINA 5) of 70 participants. Sub-subsegmental airways were CT-invisible or missing in 69 out of 70 participants; the most common number of missing sub-subsegments was 10. Participants with ≥10 missing subsegments had worse WA% ( P  < 0.0001), lumen area ( P  < 0.0001), and ventilation defect percent ( P  = 0.03) than those with <10 missing subsegments. In a multivariable model, TAC (standardized regression coefficient = 0.50; P  = 0.001) independently predicted FEV1 ( R 2  = 0.27; P  = 0.003) and, in a separate model, TAC (standardized regression coefficient = -0.53; P  < 0.0001) independently predicted airway WA% ( R 2  = 0.32; P  = 0.0001). Conclusions: TAC was significantly diminished in participants with greater asthma severity and was related to airway wall thickness and ventilation defects. Fewer airways in severe than in mild asthma challenges our understanding of airway disease in asthma.Clinical trial registered with www.clinicaltrials.gov (NCT02351141).