Airway count and emphysema assessed by chest CT imaging predicts clinical outcome in smokers

Abstract

Background: Recently, it has been shown that emphysematous destruction of the lung is associated with a decrease in the total number of terminal bronchioles. It is unknown whether a similar decrease is visible in the more proximal airways. We aimed to assess the relationships between proximal airway count, CT imaging measures of emphysema, and clinical prognostic factors in smokers, and to determine whether airway count predicts the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index.

Methods: In 50 smokers, emphysema was measured on CT scans and airway branches from the third to eighth generations of the right upper lobe apical bronchus were counted manually. The sum of airway branches from the sixth to eighth generations represented the total airway count (TAC). For each subject, the BODE index was determined. We used logistic regression to assess the ability of TAC to predict a high BODE index (≥ 7 points).

Results: TAC was inversely associated with emphysema (r = -0.54, P < .0001). TAC correlated with the modified Medical Research Council dyspnea score (r = -0.42, P = .004), FEV(1)% predicted (r = 0.52, P = .0003), 6-min walk distance (r = 0.36, P = .012), and BODE index (r = -0.55, P < .0001). The C-statistics, which correspond to the area under the receiver operating characteristic curve, for the ability of TAC alone and TAC, emphysema, and age to predict a high BODE index were 0.84 and 0.92, respectively.

Conclusions: TAC is lower in subjects with greater emphysematous destruction and is a predictor of a high BODE index. These results suggest that CT imaging-based TAC may be a unique COPD-related phenotype in smokers.

Figure 1.

Illustrative case of CT images interpolated (smooth) showing visualization of distal airway branches of the right upper lobe apical bronchus (RB1). Panels show airway branches (arrows) of the sixth (A), seventh (B) and eighth (C) generations of RB1.

Figure 2.

Bland-Altman analysis of the intrareader (A) and interreader (B) reproducibility of the total airway count (TAC) for the sixth to eighth generations of the right upper lobe apical bronchus in 20 chest CT scans. The solid line is the mean difference in TAC, and the broken lines are the upper and lower limits of agreement. (Note that fewer than 20 points are visible in either figure because in both cases some of the points are superimposed upon each other.)

Figure 3.

Airway count from generations 6 to 8 and the total airway count of the apical bronchus of the right upper lobe in subjects with emphysema. In the left y-axis, comparison of the individual airway count obtained in generations 6 to 8 between subjects with ≥ 25% (solid line with empty symbols) and < 25% (dashed line with solid symbols) emphysema is shown. In the right y-axis, comparison of the total airway count between subjects with high (○) and low (●) emphysema is also shown. Data are presented as mean ± SEM. P values were computed via t tests.

Figure 4.

Plot of total airway count (the sum of the branches from the sixth to eighth generations of the apical bronchus of the right upper lobe [RB1]) to emphysema, defined as low attenuation areas below −950 Hounsfield units in 50 smokers. See Figure 1 legend for expansion of abbreviation.

Figure 5.

Receiver operating characteristic (ROC) curves of prognostic rule based on total airway count alone (solid line; area under the ROC curve [AUC-ROC] = 0.84); emphysema alone (dotted line; AUC-ROC = 0.88); and total airway count, emphysema, and age (dashed line; AUC-ROC = 0.92). This last ROC curve was obtained using the risk-score of the logistic regression model.