Distinct Morphological Types of Small Airway Obstructions in Smokers with Emphysema and End-Stage Chronic Obstructive Pulmonary Disease

Rationale: The precise nature of small airway obstructions in chronic obstructive pulmonary disease (COPD) remains poorly understood, especially at early disease stages. Objectives: This study aimed to characterize small airway obstructions and numbers up to the terminal bronchioles (TBs) in smokers with limited emphysema and end-stage COPD. We hypothesized that obstruction subtypes would differ in morphology, nature, and number from early to end-stage COPD. Methods: Whole lungs were inflated and processed from seven control donors (control: declined for extrapulmonary reasons); from eight donors with a history of smoking, of whom three had <5% emphysema (smokers with no emphysema) and five had >5% emphysema (smokers with emphysema); and from eight patients with end-stage COPD. Micro-computed tomography of tissue was used to assess number of TBs, aerated TBs, and number and type of obstructions and was cross-correlated with histopathology. Measurements and Main Results: Obstructions were mainly present in smokers with emphysema and patients with COPD, resulting in less aerated TBs. On the basis of emphysema extent, more nonaerated TBs were present in regions with no emphysema than in regions with mild emphysema; however, destruction was more prominent in mild emphysema. Multiple types of obstructions were identified, comprising occlusions, webs, and collapses. In smokers with emphysema, obstructions primarily comprised webs and occlusions, whereas all obstruction types were present in COPD. On histopathology, obstructions were identified as mucus plugs. Conclusions: Multiple types of obstruction characterized as mucus plugs were identified in smokers with emphysema and patients with end-stage COPD. Their morphology, nature, and number evolved from smokers with emphysema to end-stage COPD. A shift from obstruction-dominant dysfunction to destruction-dominant pathology was found in smokers on the basis of emphysema presence.