 Safety issues are addressed in the AE section. There is no standardised and unanimously accepted definition of exacerbation in COPD; 4 definitions are widely used: 1 using a combination of 3 cardinal symptoms: increased dyspnea, sputum volume, and sputum purulence; 2 looking at the presence of the following patterns of symptoms during 2 consecutive days: either 2 or more of 3 major symptoms increase in dyspnoea, sputum volume and sputum purulence; or any 1 major symptom together with any 1 minor symptom increase in nasal discharge, wheeze, sore throat, cough or fever; 3 a sustained worsening of the patients condition, from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD; 4 a complex of respiratory events i.e. cough, wheezing, dyspnoea or sputum production lasting 3 days. 