Small Airway Mucous Metaplasia and Inflammation in Chronic Obstructive Pulmonary Disease

Abstract

Mucous metaplasia is an important determinant of small airway obstruction in COPD. Its relationship to small airway inflammation is poorly defined. We analyzed 4 to 6 small airways in 19 COPD patients, GOLD stages 0–4, from lobectomy or lung volume reduction surgery tissue samples. To identify intracellular mucin, periodic acid fluorescent Schiff's (PAFS) stained slides were imaged by fluorescence microscopy. PAFS+ staining area, basement membrane length (LBM), epithelial height and area were measured. Mucin was expressed as a percentage of epithelial area. Mucin volume density (MVD) was calculated as PAFS+ area divided by the product of LBM and 4/π. Airways were Giemsa stained for eosinophils and immunostained with antibodies against CD3, CD4, CD8, CD68, and neutrophil elastase (NE), and the number of positively stained cells/mm2 was quantified in the airway wall. Mucin percent correlated with CD3+ cell density (r = 0.553, P < 0.0001), and MVD correlated with CD3+ (r = 0.570, P < 0.0001) and CD8+ cell density (r = 0.279, P = 0.016). There were weak negative correlations between mucin percent as well as MVD and CD68+ cell density (r = −0.270, P = 0.02 and r = −0.245, P = 0.036). There was no relationship between epithelial mucin content and CD4+, NE+, or eosinophil cell density. CD3+ and CD8+ lymphocytic inflammation is related to small airway mucous metaplasia in COPD and may play a causative role in its development.