RATIONALE:Airway wall inflammation, IL-4, and mucus hypersecretion are thought to be associated. OBJECTIVES:To quantify bronchial inflammatory cells in smokers with chronic bronchitis (CB) with and without airflow obstruction (AO), determining the cells expressing IL-4 and IL-5 and their association with submucosal gland mucin. METHODS:We applied immunohistochemistry to identify, and double-labeling to colocalize, IL-4 and IL-5 to distinct inflammatory cells in resected bronchi from (1) 11 asymptomatic smokers (AS), (2) 11 smokers with CB, and (3) 10 smokers with CB and AO. MEASUREMENTS AND MAIN RESULTS:There were greater numbers of mucosal and gland CD45(+) leukocytes in CB (epithelium, 673/mm(2); subepithelium, 698/mm(2); gland, 517/mm(2)) than in AS (331, 237, and 178/mm(2), respectively; p < 0.01 for all) or CB + AO (375, 243, and 215/mm(2), respectively; p < 0.05 for all). There were greater numbers of subepithelial and submucosal gland plasma cells in CB (subepithelium, 110/mm(2); gland, 213/mm(2)) compared with AS (38 and 41/mm(2), respectively; p < 0.01 for both), and more subepithelial mast cells in CB (204/mm(2)) than in AS (65/mm(2); p < 0.01) or CB + AO (115/mm(2); p < 0.01). In CB, the percentage of gland occupied by mucin was positively correlated with the numbers of interstitial CD45(+) cells, plasma cells, and IL-4 protein(+) cells. In CB, 69 and 62% of gland-associated plasma cells expressed IL-4 and IL-5, respectively. CONCLUSIONS:Inflammatory cells are increased in bronchial submucosal glands and mucosa of large airways in smokers with CB. Gland-associated plasma cells express IL-4, and these likely promote mucus hypersecretion.