Mild and moderate asthma is associated with airway goblet cell hyperplasiaand abnormalities in mucin gene expression

Excessive airway mucus is an important cause of morbidity and mortality in asthma, but the relationship between accumulation of mucus and goblet cell size, number, and function is incompletely understood. To address these que stions, stored mucin in the epithelium and goblet cell size and number were measured morphometrically, and mucin gene expression was measured by polym erase chain reaction and immunohistochemistry in endobronchial biopsies fro m 13 subjects with mild and moderate asthma and from 12 healthy control sub jects. Secreted mucin was measured in induced sputum. We found that stored mucin in the airway epithelium was three times higher than normal in the su bjects with asthma (p < 0.005). Goblet cell size was similar in both groups , but goblet cell number was significantly higher in the subjects with asth ma (93,043 +/- 15,824 versus 41,959 +/- 9,230/mm(3), p < 0.05). In mild ast hma (FEV1 greater than or equal to 80% pred, n = 7), the level of stored mu cin was as high as in moderate asthma (FEV1 < 80% pred, n = 6), but the lev el of secreted mucin was significantly lower (28.4 +/- 6.3 versus 73.5 +/- 47.5 <mu>g/ml, p < 0.05). Secreted mucin was inversely correlated with stor ed mucin for the whole asthma group (r(s) = -0.78, p = 0.007). MUC5AC was t he predominant mucin gene expressed in healthy subjects and subjects with a sthma, and MUC5AC protein was increased in the subjects with asthma. We con clude that even mild asthma is associated with goblet cell hyperplasia and increased stored mucin in the airway epithelium, whereas moderate asthma is associated with increased stored mucin and secreted mucin. These findings suggest that acute degranulation of hyperplastic goblet cells may represent a mechanism for asthma exacerbations in mild and moderate asthma and that chronic degranulation of goblet cells may contribute to chronic airway narr owing in moderate asthma.