Aims: A) To explore the role of different viral infections in exacerbations of COPD and its influence on bacterial co-infection, local and systemic inflammation, airway remodelling and systemic repercussions in patients with COPD; B) To evaluate whether intensified combination therapy with inhaled corticosteroids and long-acting ?2-agonists at the onset of upper respiratory tract infection symptoms as compared to placebo decreases the incidence of exacerbation of COPD in patients receiving low maintenance dose inhaled corticosteroids/long-acting ?2-agonists, thus reducing disease associated morbidity.Significance: Exacerbations are associated with significant morbidity, mortality and health-care associated costs. Therefore, there is an urgent need to develop novel therapeutic strategies to optimize management of COPD and associated co-morbidities. At present, with the exception of influenza vaccination, there are no interventions available that specifically target viral induced infection in an attempt to reduce the prevalence and effects of exacerbations in COPD. By preventing exacerbations, the patient-driven management approach investigated in this trial might improve quality of life and reduce costs associated with COPD in spite of preserving patients' autonomy. The integrated and subsidiary projects related to the main study will provide a decisive improvement in the characterization of viral- and bacterial induced exacerbation, airway inflammation as well as remodelling mechanisms and their systemic repercussions in COPD. Scientific Frame & Methodology: Investigator-initiated and driven, double-blind randomized multinational trial. Patients with stable COPD will be included and randomized 1:1 either to intensified combination therapy with inhaled corticosteroid/ corticosteroid and long-acting ?2-agonists or to placebo. Randomization will be stratified by center. In addition, 8 integrated and subsidiary projects evaluating the domains of infection, inflammation, airway remodelling and systemic repercussions are associated with the main study. Setting: Teaching hospitals in several European countries including Switzerland, Italy, and The Netherlands. Patients: Age ? 40 years, smoking history ? 10 pack-years and moderate to very severe stable COPD (GOLD II-IV without exacerbation for ? 4 weeks), history of severe exacerbation in previous year. Excluded are patients with pulmonary conditions other than COPD as the main respiratory disease; rapid lethal disease, severe immunosuppression; known allergy or intolerance to the study medication; pregnancy.