Introduction: Airway colonization with Pseudomonas aeruginosa is frequent in severe chronic obstructive pulmonary disease (COPD) and may lead to progressive inflammatory damage. Inhaled Tobramycin Nebulizer Solution (TNS; a preservative-free formulation) is an effective therapy in chronic P aeruginosa infection in cystic fibrosis and bronchiectasis. In this study we aimed to investigate the effects of a TNS short course on inflammatory markers in bronchial secretions from multiresistant P aeruginosa-colonized patients with severe COPD. To the authors' knowledge, this is the first study to examine this in cases of severe COPD. Methods: Thirteen COPD patients (GOLD criteria 3-4; mean age 72.7 +/- 8 years; mean basal forced expiratory volume in 1 second (FEV1) 34.8%+/- 8.1%; mean FEV1/forced vital capacity 0.6 +/- 0.1) were enrolled. All patients were colonized with P aeruginosa and resistant to oral/intravenous specific antibiotics. Eosinophilic cationic protein (ECP), interleukin-1 beta (IL-1 beta), interleukin-8 (IL-8), tumor necrosis factor alfa (TNF-alpha), and cell counts were measured in spontaneous secretions before and after a 2-week TNS course (300 mg twice daily). Results: The TNS course induced a significant reduction in IL-1 beta (P < 0.03), IL-8 (P < 0.02), ECP (P < 0.01) concentrations, and in eosinophil count (P < 0.01). TNF-alpha levels, and neutrophil and lymphocyte counts were not significantly affected. The second week of treatment proved crucial in terms of efficacy. P aeruginosa density was lowered after 6 months; severe acute exacerbations were reduced by 42%. Conclusion: TNS reduced the inflammatory impact of P aeruginosa in multiresistant, P aeruginosa-colonized patients with severe COPD. A therapeutic role for TNS can be strongly suggested in these particular conditions.