Association between airway caliber changes with lung inflation and emphysema assessed by volumetric CT scan in subjects with COPD

Abstract

Background: An increase in airway caliber (airway distensibility) with lung inflation is attenuated in COPD. Furthermore, some subjects have a decrease in airway caliber with lung inflation. We aimed to test the hypothesis that airway caliber increases are lower in subjects with emphysema-predominant (EP) compared with airway-predominant (AP) CT scan subtypes. Additionally, we compared clinical and CT scan features of subjects with (airway constrictors) and without a decrease in airway caliber.

Methods: Based on GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages and CT scan subtypes, we created a control group (n = 46) and the following matched COPD groups (n = 23 each): GOLD-2-AP, GOLD-2-EP, GOLD-4-AP, and GOLD-4-EP. From the CT scans of all 138 subjects, we measured emphysema, lung volumes, and caliber changes in the third and fourth airway generations of two bronchi. We expressed airway distensibility (ratio of airway lumen diameter change to lung volume change from end tidal breathing to full inspiration) as a global or lobar measure based on normalization by whole-lung or lobar volume changes.

Results: Global distensibility in the third and fourth airway generations was significantly lower in the GOLD-2-EP and GOLD-4-EP groups than in control subjects. In GOLD-2 subjects, lobar distensibility of the right-upper-lobe fourth airway generation was significantly lower in those with EP than in those with AP. In multivariate analysis, emphysema was an independent determinant of global and lobar airway distensibility. Compared with nonconstrictors, airway constrictors experienced more dyspnea, were more hyperinflated, and had a higher percentage of emphysema.

Conclusions: Distensibility of large- to medium-sized airways is reduced in subjects with an EP CT scan subtype. Emphysema seems to alter airway-parenchyma interdependence.

Trial registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Figures

Figure 1.

A-D, Volumetric CT scan slices showing changes in airway lumen from end tidal breathing (A, C) to full inspiration (B, D). Measures of matched airways show an increase in airway lumen (A→B) in the fourth airway generation of the right-upper-lobe apical bronchus and a decrease (C→D) in the third airway generation of the right-lower-lobe posterior basal bronchus.

Figure 2.

Global airway distensibility (mean ± SEM) of the third (open bars) and the fourth (solid bars) airway generations from end tidal breathing to full inspiration in smoker control subjects and COPD groups based on GOLD stages and CT scan subtypes (AP and EP) is shown. (Global airway distensibility is defined in the Methods section.) *P < .05 vs control subjects. AP = airway-predominant CT scan subtype; EP = emphysema-predominant CT scan subtype; GOLD = Global Initiative for Chronic Obstructive Lung Disease.

Figure 3.

Lobar airway distensibility of the RUL and RLL in smoker control subjects and COPD groups based on GOLD stages and CT scan subtypes (AP and EP). A, RUL. B, RLL. Mean ± SEM lobar airway distensibility of the third (open bars) and fourth (solid bars) airway generations from end tidal breathing to full inspiration is shown. *P < .05 vs control subjects. †P < .05 vs AP. RLL = right lower lobe; RUL = right upper lobe. See Figure 2 legend for expansion of other abbreviations.

Figure 4.

Ratio of airway lumen diameter to cube root of lung volume at end tidal breathing and at full inspiration across smoker control subjects and study COPD groups (AP and EP). Mean ratio for the fourth airway generation at end tidal breathing and full inspiration for each group is shown. All the groups had similar ratios at end tidal breathing. At full inspiration, however, there was a clear trend toward decreasing ratio with increasing GOLD stage. See Figure 2 legend for expansion of abbreviations.

Figure 5.

Airway lumen diameters (mean ± SEM) of the fourth airway generation at full inspiration for control subjects and subjects with COPD with and without hyperinflation. Total lung capacity % predicted was 92%, 99%, and 131% for control, nonhyperinflated, and hyperinflated groups, respectively. There was a significant trend toward lower airway diameter with increasing total lung capacity % predicted. *P < .001 vs control subjects.