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.