Abstract: Rationale: Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lungcancer. However, the systemic inflammatory response in patients with emphysema is still unknown. Objective: To compare the plasma cytokine profiles in two groups of current or former smokers without airway obstruction:a control group of individuals without computed tomography (CT) detected emphysema vs. a study group of individualswith CT detected emphysema. Methods: Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1b, TGFa,TNFa, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors. Results: 160 current smokers and former smokers without airway obstruction participated in the study: 80 withoutemphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (20.317, p = 0.01), IL-15 (20.21, p = 0.01), IL-8 (20.180, p = 0.02) and IL-1ra (20.220, p = 0.03) in subjects with emphysema and normalspirometry. Conclusions: Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specificplasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratorydiseases.