|The influence of fluticasone on plasmacytoid dendritic cells, pDC, is unknown. In this prospective, randomized, double-blind placebo controlled study 45 smokers were treated with placebo, fluticasone or fluticasone+salmeterol. On days 0 and 28 blood and a bronchoalveolar lavage was obtained. PDC were analyzed by flow cytometry. Fluticasone+salmeterol led to a significant reduction of neutrophils and macrophages. The significant reduction of pDC was independent of salmeterol. We hypothesize that fluticasone may raise the risk of pneumonia in smokers through the reduction of pDC in the airways.