) Chronic bronchitis and COPD are characterized by chronic neutrophilic inflammation and is associated with both airway sepsis with gram-negative bacteria. Smoking is a major risk factor for development of these diseases, but only about 20 percent of smokers develop COPD. Endotoxin (ET) from gram- negative bacteria likely plays a significant role in this inflammation. Airway ET may come directly from gram-negative bacteria infecting the airway or from tobacco smoke as this is another rich source of ET. The investigators propose that responsiveness to ET also an important risk factor for development of COPD in smokers. One mechanism by which persons may be more sensitive to ET is by enhanced production of CD14, the primary receptor for ET. CD14 exists in both a cell bound form and as a soluble from in serum and airway secretions. Soluble CD14 in the airway is enhanced by acute allergic inflammation. Additionally, a C/T polymorphism has been identified at the - 159 position of the CD14 promoter gene (CD14 gene). Those persons homozygous for the T allele have been shown to have increased soluble CD14 in serum and CD14 expression on blood monocytes compared to those with CT or CC genotype. The investigators present preliminary data that demonstrates that levels of sCD14 in sputum and CD14 expression on alveolar macrophages prior to challenge with lipopolysacharride (LPS, a form of ET) correlates with neutrophil influx in sputum following inhaled LPS challenge. Also, in the nasal airway, allergen enhances granulocyte response to LPS in a fashion which correlates with local sCD14 levels. The investigators propose to examine the role that CD14 has in determining responsiveness to airway LPS and risk for COPD in smokers. First, the investigators will determine if the level of sCD14 and CD14 on macrophages is increased in volunteers with experimentally-induced and naturally occurring bronchitis and if they have increased neutrophil response to LPS. Second, the investigators determine if airway CD14 correlates with PMN response to LPS in normal volunteers. Third, the investigators will determine if airway CD14 levels and LPS response in healthy volunteers with the TT genotype for the CD14 gene is enhanced relative to that in those with the CC and CT genotype. Finally, the investigators will genotype cohorts of COPD patients and healthy smokers to determine if the T allele is a risk factor in development of COPD in those who smoke.
