For this 1-year double-blind , placebo-controlled , parallel group , multicentre , phase 3-4 trial , the Roflumilast and Exacerbations in patients receiving Appropriate Combination Therapy ( REACT ) study , we enrolled patients with severe chronic obstructive pulmonary disease from 203 centres ( outpatient clinics , hospitals , specialised pulmonologists , and family doctors ) in 21 countries .