Chest
Original ResearchEpithelial Mucin Stores Are Increased in the Large Airways of Smokers With Airflow Obstruction
Section snippets
Subjects
We enrolled 24 cigarette smokers (defined as current smoking of at least 10 cigarettes per day and a minimum history of 10 pack-years of exposure) and 19 nonsmoking control subjects (defined as < 10 pack-years of smoking with no smoking in the previous 10 years). For all subjects, inclusion criterion was age 30 to 65 years. Exclusion criteria were as follows: FEV1/FVC < 0.4; provocative concentration of methacholine resulting in 20% decrease in FEV1 from baseline value (PC20) [< 1 mg/mL];
Results
The baseline clinical characteristics of the 24 smokers and the 19 nonsmoking control subjects showed that more of the smokers were male, and that the smokers were older and had lower values for FEV1 and FEV1/FVC (Table 1). Although on average the smokers were more hyperresponsive to methacholine than the healthy subjects (Table 1), 17 of the 24 smokers had PC20 in the normal range (> 8 mg/mL). Sixteen of the 24 smokers had Dlco in the normal range (> 80% of predicted). All 19 healthy subjects
Discussion
We report that goblet cell hypertrophy and hyperplasia occur in the large airways of habitual cigarette smokers and result in epithelial mucin stores that are significantly higher than normal. The increase in stored mucin occurs because of an increase in MUC5AC and despite a decrease in MUC5B. Notably, the highest epithelial mucin stores are in the smoker subgroup with airflow obstruction, and mucin stores correlate with FEV1/FVC, even when controlling for diffusing capacity as a measure of
Acknowledgment
The authors thank the following staff at University of California, San Francisco for assistance with this study: Peggy Cadbury and Hofer Wong for recruiting subjects and for assistance with bronchoscopy; and Roderick Carter and Ronald Ferrando for assistance in tissue processing and analysis. The authors also thank Mimi Zeiger for editing the manuscript and Ingemar Carlstedt for the generous contribution of the monoclonal antibodies LUM2-3 and LUM5B-2.
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Drs. Innes and Woodruff contributed equally to the article.
This work was performed at the University of California, San Francisco.
The authors have no financial or potential conflicts of interest.
Financial support was provided by an RO1 grant (HL66564) to Dr. Fahy from the National Heart, Lung, and Blood Institute, and by a K23 award (RR17002) to Dr. Woodruff from the National Center for Research Resources. In addition, Dr. Innes was supported by an institutional training grant (HL-07185) from the National Heart, Lung, and Blood Institute.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).