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

Abstract

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-to-moderate 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-to-moderate 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 FEV(1) 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.

Figure 1. Airway measurements by MDCT

Multiple airway measurements can be performed by the Pulmonary Workstation program. Depicted are the two primary measurements used in the current study. Wall thickness is measured over the middle one-third of each segment at each centerline voxel. This value is averaged, resulting in a single wall thickness value for each segment. The average outer diameter for the segment is calculated in a similar fashion. Wall thickness % for each segment is the calculated by dividing the wall thickness by the average outer diameter. Total airway area and lumen area are similarly calculated at each centerline voxel and averaged over the middle one-third of the segment. Wall area was calculated by subtracting the lumen area from the total area. Wall area % was calculated by dividing the wall area by the total airway area.

Figure 2. Pulmonary Workstation MDCT images and bronchial biopsy from normal and severe asthma subjects

Representative images from matching Pulmonary Workstation MDCT analysis and hematoxlyn-eosin (H&E) sections from an endobronchial biopsy from a normal control subject (Panel A & C) and a severe asthma subject (Panel B & D) are demonstrated. The MDCT analysis was performed using the Pulmonary Workstation software (VIDA) and a screen capture of the cross-sectional MDCT image is demonstrated. The H&E sections were obtained from endobronchial biopsies that were processed as described in Methods. The epithelial layer (Epi), lamina reticularis (LR) and the basement membrane (dashed line) are indicated.

Figure 3. MDCT wall thickness % and wall area % are correlated with airway remodeling

In a subset of patients (n = 32), endobronchial biopsies were performed. Epithelial thickness was measured in μm and normalized for the length of basement membrane, resulting in an epithelial ratio. These morphometric measurements were then correlated with the radiographic indices WT% and WA%. (a) Wall thickness % is correlated with epithelial thickness (r = 0.47, p = 0.007). (b) Wall area % is correlated with epithelial thickness (r = 0.52, p = 0.003 respectively).