Koo, Hyun-Kyoung, Vasilescu, Dragos M., Booth, Steven, Hsieh, Aileen, Katsamenis, Orestis L., Fishbane, Nick, Elliott, W. Mark, Kirby, Miranda, Lackie, Peter, Sinclair, Ian, Warner, Jane A., Cooper, Joel D., Coxson, Harvey O., Pare, Peter D., Hogg, James C. and Hackett, Tillie-Louise (2018) Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study. The Lancet Respiratory Medicine, 6 (8), 591-602. (doi:10.1016/S2213-2600(18)30196-6).
Abstract
Background: the concept that the small conducting airways <2mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the literature. It has also been shown that the last generation of small conducting airways, terminal bronchioles, are significantly destroyed in patients with very-severe COPD. What is not known is at what stage in the development of COPD the loss of small airways occurs, or how loss of terminal and transitional (first generation of respiratory airways) bronchioles - relates to the loss alveolar surface area that characterizes emphysema.
Methods: a novel multi-resolution computed tomography (CT) imaging protocol was applied to systematically, randomly sampled whole lungs or lobes of smokers with normal lung function (n=10), mild (n=10), moderate (n=8), and very-severe COPD (n=6). The 34 lung specimens provided 262 lung tissue samples for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (Lm), alveolar surface area.
Findings: the new data demonstrate that 41% of terminal bronchioles, 57% of transitional bronchioles, and 37% of the alveolar surface area is lost in patients with mild and moderate COPD compared to control smokers, before any emphysematous changes can be detected by CT. We also show these pathological changes correlate with lung function decline. Importantly, we demonstrate that loss of terminal and transitional bronchioles occurs in regions of the lung that have no loss of alveolar surface area. Further, we validated using histology, that the surviving small airways have thickened walls and narrowed lumens which become more obstructed as the disease progresses.
Interpretation: these data demonstrate that small airways disease is an early pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention in mild and moderate COPD patients is most likely required for disease modification.
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