The comparative effectiveness of initiating fluticasone/salmeterol combination therapy via pMDI versus DPI in reducing exacerbations and treatment escalation in COPD: a UK database study

Int J Chron Obstruct Pulmon Dis. 2017 Aug 17;12:2445-2454. doi: 10.2147/COPD.S141409. eCollection 2017.


Chronic obstructive pulmonary disease (COPD), a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS)/long-acting β-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs. Our aim was to compare effectiveness, in terms of moderate/severe COPD exacerbations and long-acting muscarinic antagonist (LAMA) prescriptions, for COPD patients initiating fluticasone propionate (FP)/salmeterol xinafoate (SAL) via pMDI versus DPI at two doses of FP (500 and 1,000 μg/d) using a real-life, historical matched cohort study. COPD patients with ≥2 years continuous practice data, ≥2 prescriptions for FP/SAL via pMDI/DPI, and no prescription for ICS were selected from the Optimum Patient Care Research Database. Patients were matched 1:1. Rate of moderate/severe COPD exacerbations and odds of LAMA prescription were analyzed using conditional Poisson and logistic regression, respectively. Of 472 patients on 500 μg/d, we observed fewer moderate/severe exacerbations in patients using pMDI (99 [42%]) versus DPI (115 [49%]) (adjusted rate ratio: 0.71; 95% confidence interval: 0.54, 0.93), an important result since the pMDI is not licensed for COPD in the UK, USA, or China. At 1,000 μg/d, we observed lower LAMA prescription for pMDI (adjusted odds ratio: 0.71; 95% confidence interval: 0.55, 0.91), but no difference in exacerbation rates, potentially due to higher dose of ICS overcoming low lung delivery from the DPI.

Keywords: COPD; diabetes; dose-response; exacerbations; inhaled steroid/LABA combination; inhaler type; pneumonia.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Aged
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Comparative Effectiveness Research
  • Databases, Factual
  • Disease Progression
  • Dry Powder Inhalers*
  • Female
  • Fluticasone-Salmeterol Drug Combination / administration & dosage*
  • Fluticasone-Salmeterol Drug Combination / adverse effects
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Humans
  • Logistic Models
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Metered Dose Inhalers*
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage
  • Odds Ratio
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Retrospective Studies
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • United States


  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Fluticasone-Salmeterol Drug Combination
  • Glucocorticoids
  • Muscarinic Antagonists