Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

Abstract

Asthma is a disease characterized by ventilation heterogeneity (VH). Anumber of studies have demonstrated that VH markers derived by using impulse oscillometry (IOS) or multiple-breath washout (MBW) are associated with key asthmatic patient-related outcome measures and airways hyperresponsiveness. However, the topographical mechanisms of VH in the lung remain poorly understood. We hypothesized that specific regionalization of topographical small-airway disease would best account for IOS- and MBW-measured indices in patients. We evaluated the results of paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n=41) and healthy (n=11) volunteers to understand the determinants of clinical VH indices commonly reported by using IOS and MBW. Parametric response mapping (PRM) was used to calculate the functional small-airways disease marker PRMfSAD and Hounsfield unit (HU)-based density changes from total lung capacity to functional residual capacity (ΔHU); gradients of ΔHU in gravitationally perpendicular (parallel) inferior-superior (anterior-posterior) axes were quantified. The ΔHU gradient in the inferior-superior axis provided the highest level of discrimination of both acinar VH (measured by using phase 3 slope analysis of multiple-breath washout data) and resistance at 5Hz minus resistance at 20Hz measured by using impulse oscillometry (R5-R20) values. Patients with a high inferior-superior ΔHU gradient demonstrated evidence of reduced specific ventilation in the lower lobes of the lungs and high levels of PRMfSAD. Acomputational small-airway tree model confirmed that constriction of gravitationally dependent, lower-zone, small-airway branches would promote the largest increases in R5-R20 values. Ventilation gradients correlated with asthma control and quality of life but not with exacerbation frequency. Lower lobe-predominant small-airways disease is a major driver of clinically measured VH in adults with asthma.