Airway remodeling measured by multidetector CT is increased in severe asthma and correlates with pathology

Background: To prospectively apply an automated, quantitative three-dimensional approach to imaging and airway analysis to assess airway remodeling in asthma patients. Methods: Using quantitative software (Pulmonary Workstation, version 0.139; VIDA Diagnostics; Iowa City, IA) that enables quantitative airway segment measurements of low-dose, thin-section (0.625 to 1.25 mm), multidetector-row CT (MDCT) scans, we compared airway wall thickness (WT) and wall area (WA) in 123 subjects participating in a prospective multicenter cohort study, the National Institutes of Health Severe Asthma Research Program (patients with severe asthma, n = 63; patients with mild-to-moderate asthma, n = 35); and healthy subjects, n = 25). A subset of these subjects underwent fiberoptic bronchoscopy and endobronchial biopsies (n = 32). WT and WA measurements were corrected for total airway diameter and area: WT and WA, respectively. Results: Subjects with severe asthma had a significantly greater WT% than patients with mild-tomoderate asthma and healthy subjects (17.2 ± 1.5 vs 16.5 ± 1.6 [p = 0.014] and 16.3 ± 1.2 [p = 0.031], respectively) and a greater WA percentage (WA%) compared to patients with mild-tomoderate asthma and healthy subjects (56.6 ± 2.9 vs 54.7 ± 3.3 [p = 0.005] and 54.6 ± 2.4 [p = 0.003], respectively). Both WT% and WA% were inversely correlated with baseline FEV1 percent predicted (r= -0.39, p < 0.0001 and r= -0.40, p < 0.0001, respectively) and positively correlated with response to a bronchodilator (r = 0.28, p = 0.002 and r = 0.35, p < 0.0001, respectively). The airway epithelial thickness measure on the biopsy sample correlated with WT% (r = 0.47; p = 0.007) and WA% (r = 0.52; p = 0.003). In the same individual, there is considerable regional heterogeneity in airway WT. Conclusion: Patients with severe asthma have thicker airway walls as measured on MDCT scan than do patients with mild asthma or healthy subjects, which correlates with pathologic measures of remodeling and the degree of airflow obstruction. MDCT scanning may be a useful technique for assessing airway remodeling in asthma patients, but overlap among the groups limits the diagnostic value in individual subjects.