Dysfunctional lung anatomy and small airways degeneration in COPD

Chronic obstructive pulmonary disease (COPD) is characterized by incompletely reversible airflow obstruction. Direct measurement of airways resistance using invasive techniques has revealed that the site of obstruction is located in the small conducting airways, ie, bronchioles with a diameter < 2 mm. Anatomical changes in these airways include structural abnormalities of the conducting airways (eg, peribronchiolar fibrosis, mucus plugging) and loss of alveolar attachments due to emphysema, which result in destabilization of these airways related to reduced elastic recoil. The relative contribution of structural abnormalities in small conducting airways and emphysema has been a matter of much debate. The present article reviews anatomical changes and inflammatory mechanisms in small conducting airways and in the adjacent lung parenchyma, with a special focus on recent anatomical and imaging data suggesting that the initial event takes place in the small conducting airways and results in a dramatic reduction in the number of airways, together with a reduction in the cross-sectional area of remaining airways. Implications of these findings for the development of novel therapies are briefly discussed.