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<h4>Rationale</h4>Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown.<h4>Objective</h4>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 individuals with CT detected emphysema.<h4>Methods</h4>Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1β, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors.<h4>Results</h4>160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (-0.317, p = 0.01), IL-15 (-0.21, p = 0.01), IL-8 (-0.180, p = 0.02) and IL-1ra (-0.220, p = 0.03) in subjects with emphysema and normal spirometry.<h4>Conclusions</h4>Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma 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 respiratory diseases.