PROJECT SUMMARY/ABSTRACT Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the US1,2. Although COPD occurs predominantly in smokers, it is unknown why only a minority of smokers (~20-40%) develops chronic airflow limitation or destruction of distal airspaces (emphysema). Identification molecular profiles from current or former smokers who are likely to progress is a crucial step in understanding the pathogenesis of COPD and emphysema. There are very few publications that describe COPD biomarkers in large, well phenotyped cohorts that include a significant number of African Americans. This study will leverage large NIH- supported cohorts (COPDGene, SPIROMICS, and MESA-Lung) that have large number of well-characterized African Americans subjects with or at risk for COPD. Since the subjects have stored plasma and have been followed for 7-10 years with extensive clinical, physiologic, and imaging, we can very cost-effectively apply a proteomic approach. Furthermore, because the cohorts have other valuable Omics data, we can integrate the proteomic findings with whole genome sequencing and other advanced molecular studies such as genomics. This knowledge may help develop novel diagnostic tests and therapies for early prevention and treatment of COPD and will identify any markers that are specific to smoking-related lung disease in African Americans.