1. 1) Initiation of ICS therapy or 2) Increase ICS therapy (50% dose increase) Baseline period: 1 year Outcome period: 2 years Extra-fine HFA-BDP via MDI confounding factor definition patient characterisation cohort matching FP via MDI Smokers and ex-smokers with COPD ≥ 40 years old Price et al Int J Chron Obstruct Pulmon Dis. 2014;9:1163-1186 1

2. The small airways in COPD A, Normal small airway. B, Abnormal small airway with airway remodeling in COPD. The airway is narrowed by deposition in the interstitial space. Postma et al CHEST 2011;139(2):412-413 2

3. Baseline COPD therapies Price et al Int J Chron Obstruct Pulmon Dis. 2014;9:1163-1186 3

4. Qvar vs. fluticasone in COPD: UK database study (contd.) Exacerbations, treatment success and therapy FP = 1.00 EF HFA-BDP >1EF HFA-BDP <1 Odds ratios / rate ratios (95%CI) 0.20.511.535 Adherence to therapy Change in therapy Treatment success Exacerbations Average Daily ICS Dose (mcg) Median [IQR] EF HFA-BDPFPp value Initiation cohort315.1 [150.7, 458.9]435.6 [205.5, 739.7]< 0.001 Step-up cohort438.4 [274.0, 619.2]534.3 [328.8, 842.5]< 0.001 Odds ratios / rate ratios (95%CI) 0.20.511.535 FP = 1.00 EF HFA-BDP >1EF HFA-BDP <1 INITIATION COHORT N = 334 / cohort STEP-UP COHORT N = 189 / cohort Price et al Int J Chron Obstruct Pulmon Dis. 2014;9:1163-1186 4