Small Airways Disease in Pre-COPD with Emphysema: A Cross-Sectional Study.

RATIONALE: Small airway disease is an important pathophysiological feature of COPD. Recently, pre-COPD has been put forward as potential precursor stage of COPD, defined by abnormal spirometry or significant emphysema on CT in the absence of airflow obstruction.

METHODS: We collected whole lungs/lung lobes from patients with emphysematous pre-COPD (n=10), COPD GOLD I (n=6), GOLD II (n=6), GOLD III/IV (n=7) and controls (n=10) which were analyzed using CT and microCT. The degree of emphysema and the number and morphology of small airways was compared between the different groups and further correlations were investigated with physiologic measures. Airway and parenchymal pathology was also validated with histopathology.

MEASUREMENTS AND MAIN RESULTS: The number of transitional bronchioles (TrB)/mL and terminal bronchioles (TB)/mL was significantly lower in pre-COPD, GOLD I, GOLD II and GOLD III/IV compared to controls. In addition, the number of alveolar attachments of the TrB and TB was also lower in pre-COPD and all COPD groups compared to controls. We did not find any differences between the pre-COPD and COPD group in either CT or microCT measures. The % of emphysema on CT showed the strongest correlation with the number of small airways, also in patients without airflow obstruction. Histopathology showed an increase in the mean chord length and a decrease in the alveolar surface density in pre-COPD and all GOLD stages compared to control.

CONCLUSION: Lungs of patients with emphysematous pre-COPD already show lower small airway number and airway remodeling and in the absence of physiologic airway obstruction.