Quantitative assessment of multiscale structural and functional alterations in asthmatic populations

Relationships between structural and functional variables in asthmatic lungs at local and global (or lobar) levels remain to be discovered. This study aims to investigate local alterations of structural variables [bifurcation angle, circularity, airway wall thickness (WT), and hydraulic diameter (Dh)] in asthmatic subjects, and their correlations with other imaging and pulmonary function test-based global and lobar metrics, including lung shape, air-trapping, regional volume change, and more. Sixty-one healthy subjects, and 67 nonsevere and 67 severe asthmatic subjects were studied. The structural variables were derived from computed tomography images at total lung capacity (TLC). Air-trapping was measured at functional residual capacity, and regional volume change (derived from image registration) was measured between functional residual capacity and TLC. The tracheal diameter and WT predicted by 61 healthy subjects were used to normalize the Dh and WT. New normalization schemes allowed for the dissociation of luminal narrowing and wall thickening effects. In severe asthmatic subjects, the alteration of bifurcation angle was found to be correlated with a global lung shape at TLC, and circularity was significantly decreased in the right main bronchus. While normalized WT increased especially in the upper lobes of severe asthmatic subjects, normalized Dh decreased in the lower lobes. Among local structural variables, normalized Dh was the most representative variable, because it was significantly correlated with alterations of functional variables, including pulmonary function test's data. In conclusion, understanding multiscale phenomena may help to provide guidance in the search for potential imaging-based phenotypes for the development and outcomes assessment of therapeutic intervention.