Uncontrolled asthma phenotypes defined from parameters using quantitative CT analysis

Objective Asthma is a heterogeneous disease with diverse clinical phenotypes that have been identified via cluster analyses. However, the classification of phenotypes based on quantitative CT (qCT) is poorly understood. The study was conducted to investigate CT determination of uncontrolled asthma phenotypes. Methods Sixty-five patients with uncontrolled asthma (37 with severe asthma, 28 with non-severe asthma) underwent detailed clinical, laboratory, and pulmonary function tests, as well as qCT analysis. Twenty-five healthy subjects were also included in this study and underwent clinical physical examinations, pulmonary function tests, and low-dose CT scans. Results The mean lumen area/body surface area ratio was smaller in patients with severe uncontrolled asthma compared with that in healthy subjects (9.84 mm 2 [SD, 2.57 mm 2 ], 11.96 mm 2 [SD, 3.09 mm 2 ]; p = 0.026). However, the percentage of mean wall area (WA) was greater (64.39% [SD, 2.55%], 62.09% [SD, 3.81%], p = 0.011). Air trapping (measured based on mean lung density and VI −856 [%] on expiratory scan) was greater in patients with severe uncontrolled asthma than in those with non-severe uncontrolled asthma and was higher in all patients with uncontrolled asthma than that in healthy subjects (all p < 0.001). Three CT-determined uncontrolled asthma phenotypes were identified. Cluster 1 had mild air trapping with or without proximal airway remodeling. Cluster 2 had moderate air trapping with or without proximal airway remodeling. Cluster 3 had severe air trapping with proximal airway remodeling. Conclusions There was obvious air trapping and proximal airway remodeling in patients with severe uncontrolled asthma. The three CT-determined uncontrolled asthma phenotypes might reflect underlying mechanisms of disease in patient stratification and in the different stages of disease development. Key Points • Obvious air trapping and proximal airway remodeling were present in patients with severe uncontrolled asthma. • CT air trapping indices showed a good correlation with disease duration, total IgE, atopy, and OCS and ICS doses, and were even more strongly correlated with clinical lung function. • Three CT-determined uncontrolled asthma phenotypes were identified, which might reflect underlying mechanisms of disease in patient stratification and in the different stages of disease development.