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

Claudia L. Ordoñez, Ramin Khashayar, Hofer H. Wong, Ron Ferrando, Reen Wu, Dallas M. Hyde, Jon A. Hotchkiss, Yifan Zhang, Alexander Novikov, Gregory Dolganov, John V. Fahy

Research output: Contribution to journalArticle

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Abstract

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 questions, stored mucin in the epithelium and goblet cell size and number were measured morphometrically, and mucin gene expression was measured by polymerase chain reaction and immunohistochemistry in endobronchial biopsies from 13 subjects with mild and moderate asthma and from 12 healthy control subjects. Secreted mucin was measured in induced sputum. We found that stored mucin in the airway epithelium was three times higher than normal in the subjects with asthma (p < 0.005). Goblet cell size was similar in both groups, but goblet cell number was significantly higher in the subjects with asthma (93,043 ± 15,824 versus 41,959 ± 9,230/mm3, p < 0.05). In mild asthma (FEV1 ≥ 80% pred, n = 7), the level of stored mucin was as high as in moderate asthma (FEV1 < 80% pred, n = 6), but the level of secreted mucin was significantly lower (28.4 ± 6.3 versus 73.5 ± 47.5 μg/ml, p 0.05). Secreted mucin was inversely correlated with stored mucin for the whole asthma group (rs = -0.78, p = 0.007). MUC5AC was the predominant mucin gene expressed in healthy subjects and subjects with asthma, and MUC5AC protein was increased in the subjects with asthma. We conclude 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 narrowing in moderate asthma.

Original languageEnglish (US)
Pages (from-to)517-523
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume163
Issue number2
StatePublished - 2001

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Goblet Cells
Mucins
Hyperplasia
Asthma
Gene Expression
Cell Size
Epithelium
Cell Count
Mucus
Healthy Volunteers
Sputum

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. / Ordoñez, Claudia L.; Khashayar, Ramin; Wong, Hofer H.; Ferrando, Ron; Wu, Reen; Hyde, Dallas M.; Hotchkiss, Jon A.; Zhang, Yifan; Novikov, Alexander; Dolganov, Gregory; Fahy, John V.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 2, 2001, p. 517-523.

Research output: Contribution to journalArticle

Ordoñez, CL, Khashayar, R, Wong, HH, Ferrando, R, Wu, R, Hyde, DM, Hotchkiss, JA, Zhang, Y, Novikov, A, Dolganov, G & Fahy, JV 2001, 'Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression', American Journal of Respiratory and Critical Care Medicine, vol. 163, no. 2, pp. 517-523.
Ordoñez, Claudia L. ; Khashayar, Ramin ; Wong, Hofer H. ; Ferrando, Ron ; Wu, Reen ; Hyde, Dallas M. ; Hotchkiss, Jon A. ; Zhang, Yifan ; Novikov, Alexander ; Dolganov, Gregory ; Fahy, John V. / Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. In: American Journal of Respiratory and Critical Care Medicine. 2001 ; Vol. 163, No. 2. pp. 517-523.
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AU - Ordoñez, Claudia L.

AU - Khashayar, Ramin

AU - Wong, Hofer H.

AU - Ferrando, Ron

AU - Wu, Reen

AU - Hyde, Dallas M.

AU - Hotchkiss, Jon A.

AU - Zhang, Yifan

AU - Novikov, Alexander

AU - Dolganov, Gregory

AU - Fahy, John V.

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