Quantitative computed tomography–derived clusters: Redefining airway remodeling in asthmatic patients

• Published in: Journal of allergy and clinical immunology Vol. 133; no. 3; pp. 729 - 738.e18
• Main Authors: Gupta, Sumit, Hartley, Ruth, Khan, Umair T., Singapuri, Amisha, Hargadon, Beverly, Monteiro, William, Pavord, Ian D., Sousa, Ana R., Marshall, Richard P., Subramanian, Deepak, Parr, David, Entwisle, James J., Siddiqui, Salman, Raj, Vimal, Brightling, Christopher E.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2014; Elsevier; Elsevier Limited; Mosby
• Subjects: Adult; Aged; Airway Remodeling; Allergy and Immunology; Asthma; Asthma - diagnostic imaging; Asthma - pathology; Asthma - physiopathology; Asthma and Lower Airway Disease; Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; Cluster Analysis; distal airway; Drug therapy; Female; fractal analysis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; Lung - physiopathology; Male; Medical sciences; Methods; Middle Aged; Phenotype; phenotypes; Pneumology; Quality of life; quantitative imaging; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Software; Statistical analysis; Tomography; Tomography, X-Ray Computed - methods; Variables; quantitative imaging; ATS; RB1; fractal analysis; RV; LV; TLC; WA; HU; BSA; distal airway; Dsc; MLD E/I; VI−850/−950 E-I; cluster analysis; Pi10; WV; De; airway remodeling; ICC; VI−850 E-I; ROI; Asthma; CT; Dsce; phenotypes; VI; LA; FRC; Dav; Po20; Averaged fractal dimension; Hypothetical airways with outer airway perimeter of 20 mm; D e; D av; Computed tomography; Voxel index; VI −850/−950 E-I; Mean lung density expiratory/inspiratory ratio; VI−850 change on paired inspiratory and expiratory CT scan; Right upper lobe apical segmental bronchus; Intraclass correlation coefficient; Lumen area; D sc; Lumen volume; Wall volume; Functional residual capacity; Hypothetical airway with internal perimeter of 10 mm; Region of interest; Body surface area; Total lung capacity; Voxel index change of percent voxels between −950 and −850 HU on paired inspiratory and expiratory CT scan; American Thoracic Society; VI −850 E-I; Residual volume; Slope-corrected fractal dimension; Wall area; D sce; Hounsfield units; Most efficient cover fractal dimension; Slope-corrected most-efficient covering fractal dimension; Human; Lung disease; Immunopathology; Radiodiagnosis; Respiratory disease; Remodeling; Respiratory system; Respiratory tract; Phenotype; Immunology; Distal; Bronchus disease; Medical imagery; Computerized axial tomography; Obstructive pulmonary disease; Quantitative analysis
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.09.039

Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)–assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes. Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm3 [SD, 112.6 mm3], 259.0 mm3 [SD, 53.3 mm3], 366.4 mm3 [SD, 195.3 mm3], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies.