Small airway obstruction is a major feature of COPD besides alveolar emphysema. Our aim was to investigate the lower airway zones up to the functional terminal bronchioles (TB) in a spectrum from healthy and early emphysematous to end-stage COPD lungs.

Explanted lungs from 9 healthy donors, rejected for extrapulmonary reasons, 10 donors radiologically and histologically characterized with emphysema (EMPH) and 9 COPD patients (GOLD 4) were frozen at TLC and processed in small cylinders (1.4 cm diameter). Of each lung, 4 samples were scanned by microCT (resolution 10 µm). TB were counted, discriminating ventilated and non-ventilated TB, i.e. with occlusions upstream, or in the TB (a).

Total number of TB/mL decreased in EMPH (p=0.0715) and in COPD (p=0.0003). In donor, EMPH and COPD a progressive decrease in ventilated TB was seen in 26%, 36% and 63% of samples, respectively. In 6% donor, 12% EMPH and 21% COPD samples no TB were present. The number of ventilated TB were significantly lower in EMPH (p=0.001) and COPD (p<0.0001) lungs compared to donor lungs (b). In cores with TB, the percentage of non-ventilated TB was significantly increased in COPD (p<0.0001) and to a lesser extent in EMPH, compared to donor (c).

Functional TB are decreased in early emphysema, and increasingly more non-ventilated TB are seen in early EMPH and COPD lungs, despite having less TB. This will lead to further progressive dysfunction of the bronchioles.