LSC - 2024 - Mucin overexpression in (pre-)COPD lung tissue correlates with degree of emphysema

<bold>Background:</bold> Mucus hypersecretion and plugging contributes to COPD initiation, progression, exacerbations, and mortality. While secreted mucins 5AC and 5B are the major components of mucus in the airways, transmembrane mucins also contribute to airway epithelial barrier (dys)function. How (transmembrane) mucin expression relates to COPD pathophysiology is not entirely clear yet. <bold>Methods:</bold> We analyzed mucin (MUC) 1, 4, 5AC, 5B, and 13 expression in human lung tissue from 12 controls (never and ever smoking), 13 pre-COPD patients (>5% emphysema on CT and no physiological obstruction), and 28 COPD patients with different disease severity (GOLDI=10, GOLDII=9, GOLDIII/IV=9) by qPCR. Two lung tissue cores per patient were selected and scanned with microCT to obtain surface density and the number of terminal bronchioles/mL. <bold>Results:</bold> MUC4 and 5B expression negatively correlated with surface density (R=-0.24;-0.30, p=0.014;0.002 resp.), while MUC1 expression positively correlated with surface density (R=0.23, p=0.038). In COPD patients alone, MUC4, 5B, and 13 negatively correlated with surface density (R=-0.28;-0.31;-0.31, p=0.034;0.015;0.026 resp.) and MUC1 positively correlated with surface density (R=0.56, p=0.0001). In addition, MUC5B and 13 negatively correlated with number of terminal bronchioles/mL (R=-0.40;-0.33, p=0.008;0.037 resp.). Finally, we found a strong positive correlation between all mucins besides MUC1. <bold>Conclusion:</bold> Our data shows that mucin overexpression may contribute to the development of small airway disease and emphysema in (pre-)COPD patients. Mucin 1 may have a protective role herein. Moreover, we report a co-expression of both transmembrane and secreted mucins in human lung tissue.