This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our protocol (HIC 11928) has been established to investigate the genetic vulnerability to develop pulmonary COPD with cigarette smoke exposure. To this date, our protocol has shown that cigarette exposed subjects with emphysematous COPD have blunted leukotriene production when compared to other cigarette smoke exposed subjects without emphysematous COPD. This observation has raised more refined questions concerning subjects who are clinically healthy but have a current or past history of significant primary or secondhand cigarette smoke exposure. If our observations to this date would hold true, we expect that among these healthy subjects, some may have blunted leukotriene production in their blood while others may have robust leukotriene production. Furthermore, those with blunted leukotriene production may have subclinical lung disease (either emphysematous or non-emphysematous COPD) from cigarette smoke exposure while others with robust leukotriene production may have normal lung even after significant cigarette smoke exposure. In combination, identification of these two distinctive groups can further support our original hypothesis that leukotrienes may be protective molecules in the pathogenesis of COPD. In order to confirm our refined hypothesis, we will administer a Cardiopulmonary Stress Test (CPT) in the GCRC subject inclusion criteria Group 5 and 6. Our hypothesis is that: 1. CPT will identify two subgroups of cigarette smoke exposed healthy subjects a. Subjects with no clinical abnormalities and with normal CPT. b. Subjects with no clinical abnormalities but with abnormal CPT. 2. Results of CPT will correlate with out biochemical analysis of leukotriene biology a. Subjects with no clinical abnormalities and with normal CPT will have robust leuktoriene production in blood. b. Subjects with no clinical abnormalities and with abnormall CPT will have blunted leukotriene production in blood.
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