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(Chest. 2006;130:1102-1108.)
© 2006 American College of Chest Physicians

Epithelial Mucin Stores Are Increased in the Large Airways of Smokers With Airflow Obstruction*

Anh L. Innes, MD; Prescott G. Woodruff, MD; Ronald E. Ferrando, MA; Samantha Donnelly, PhD; Gregory M. Dolganov, PhD; Stephen C. Lazarus, MD and John V. Fahy, MD

* From the Department of Medicine, Division of Pulmonary and Critical Care Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA.

Correspondence to: John V. Fahy, MD, Box 0111, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143; e-mail: john.fahy{at}ucsf.edu.

Abstract

Background: Habitual cigarette smoking is associated with chronic mucus hypersecretion, but the relationship between mucus abnormalities and airflow obstruction in smokers is uncertain.

Methods: We collected bronchial biopsy samples and epithelial brushings from 24 smokers with and without airflow obstruction and 19 nonsmoking healthy control subjects. Epithelial mucin stores, mucin immunostains, and goblet cell morphology were quantified in bronchial biopsy samples using stereology, and mucin gene expression was quantified in epithelial brushings using real-time reverse transcriptase-polymerase chain reaction.

Results: Goblet cell size and number were higher than normal in smokers (both p < 0.05), leading to a 2.2-fold increase in the volume of stored mucin in the epithelium per surface area of basal lamina (1.94 ± 0.31 µm3/µm2 vs 4.32 ± 0.55 µm3/µm2 in control subjects vs smokers, p = 0.001). The increase in stored mucin occurred because of an increase in MUC5AC (p = 0.018) and despite a decrease in MUC5B (p < 0.0001). Stored mucin was significantly higher in the subgroup of smokers with airflow obstruction (p = 0.029) and correlated with FEV1/FVC even when controlling for diffusing capacity as a measure of emphysema (p = 0.034).

Conclusions: Epithelial mucin stores are increased in habitual smokers because of goblet cell hypertrophy and hyperplasia, and the pattern of mucin gene expression is abnormal. The highest epithelial mucin stores are found in smokers with airflow obstruction, suggesting a mechanistic link between epithelial mucin dysregulation and airflow obstruction.

Key Words: airway epithelium • cigarette smoke • COPD • mucin • MUC2 • MUC6 • MUC5AC • MUC5B • stereology




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