Macrophage inflammation and association with structural remodeling in pre-COPD

<bold>Introduction:</bold> Chronic bronchial and parenchymal inflammation are considered important in the pathophysiology of COPD. Pre-COPD has been put forward as potential precursor stage of COPD. We have previously demonstrated that there is a lower number of terminal and transitional bronchioles in pre-COPD compared to control, in the abscence of airway obstruction. <bold>Methods:</bold> We collected surgical excision specimens (lobectomy) from patients with pre-COPD (n=10), COPD GOLD I (n=6), GOLD II (n=6) and controls (n=7). MicroCT was performed on extracted tissue samples, for quantification of the number of transitional bronchioles/mL and surface density, number of alveolar attachments and airway wall thickess on two different locations with the lung. On the same tissue, immunohistochemical staining with CD68 was performed. The macrophages were counted on 10 random high power fields and averaged. <bold>Results:</bold> We observed an increase in the number of macrophages in all investigated groups including pre-COPD compared to controls (all p<0.05). In addition, the number of macrophages significantly correlated with the number of transitional bronchioles (p=0.011, R=-0.34), the surface density as a marker of emphysema (p=0.0001, R=-0.50), the number of alveolar attachments (p=0.0003, R=-0.48) and airway thickness (p=0.0024, R=0.41). <bold>Conclusion:</bold> An increase in the number of macrophages was observed already in pre-COPD compared to controls. In addition, the number of macrophages correlated significantly with loss in transitional bronchioles, but also with parameters reflecting airway and parenchymal remodeling demonstrating that this type of inflammation is already crucial in the very early stages of COPD development.