A Study of Inhalation of 20,000 EU CCRE and MCC in Otherwise Healthy Individuals Who Are Current Cigarette Smokers

The purpose of this study is to determine the range of neutrophil response (influx of PMNs to the airways as determined in sputum) after inhalation of CCRE (20,000 EU), shown in previous studies of healthy, nonsmoking volunteers as well as in a limited number of otherwise healthy smokers to be well tolerated. This dose induces measurable increases in neutrophil content of induced sputum that can be employed to screen large populations for susceptibility to the inflammatory effect of inhaled endotoxin. Limitations of the understanding of actions of inflammatory stimuli on airway function are likely due to the fact that functional assessments of dynamic airway response /in vivo/ have generally been limited to those based on spirometry and examination of airway samples for assessment of cells and mediator content. Slowing of mucociliary clearance (MCC), a key component of airway defense, can be induced by inflammation and almost certainly contribute to mucus plugging and decreased clearance of inhaled irritants. Measures of mucociliary clearance (MCC), by inhalation of radiolabeled particles to label airway surface liquid, suggest that clearance of secretions is impaired to a mild degree in smokers and more severely in patients hospitalized for acute exacerbations.