Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease The REDUCE Randomized Clinical Trial

JD Leuppi. JAMA 2013; 309(21): 2223-2231. doi:10.1001/jama.2013.5023

Clinical Question

  • Is short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation as good as conventional (14 days) treatment in clinical outcome and does it decrease the overall exposure to steroids?


  • Randomised
  • Multi-centre
  • Placebo-controlled
  • Double-blind
  • Non-inferiority


  • 5 teaching hospital Emergency Departments in Switzerland
  • March 2006 to February 2011


  • Inclusion
    • Exacerbation of COPD as defined as 2 of the following
      • Change in baseline dyspnoea
      • Cough
      • Change in sputum quantity or purulence
      • Age over 40
      • Smoking history of 20 pack years or more
  • Exclusion
    • History of asthma
    • FEV1:FVC ratio > 70% (evaluated by bedside post bronchodilator spirometry prior to randomisation)
    • Radiological diagnosis of pneumonia
    • Estimated survival of less than 6 months due to severe co-morbidities
    • Pregnancy or lactation
    • Inability to give written consent
    • ++ already on steroids not an exclusion
  • 717 patients assessed, 314 randomised
  • 15% absolute difference defined as threshold for non-inferiority


  • 40mg of intravenous methylprednisolone on day 1
  • 40mg of oral prednisolone from day 2 to day 5.
  • Placebo day 6 to 14


  • 40mg of intravenous methylprednisolone on day 1
  • 40mg of oral prednisolone from day 2 to day 14.
All patients in both group also received a 7 day course of broad-spectrum antibiotics as well as standard nebulised and inhaled bronchodilators plus inhaled glucocorticoids


  • Primary outcome: No significant difference in exacerbation rates during the 6 month follow up period
    • 35.9% in 5-day group vs 36.8% in the 14-day group
  • Secondary outcomes: No significant difference in:
    • All cause mortality
    • Clinical outcomes (dyspnoea questionnaire)
      • Change in FEV1
      • Need for mechanical ventilation (intubation or non-invasive ventilation)
    • Subjective outcomes
      • Patient reported overall performance
      • Clinical performance
    • Complications of steroids
      • Glucocorticoid-associated adverse effects
      • Hyperglycaemia
      • Hypertension
      • Newly diagnosed infection
      • Other potential glucocorticoid-related adverse events
  • Significant reduction in mean cumulative corticosteroid dose in intervention group (379mg vs 793mg)

Authors’ Conclusions

  • In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was non-inferior to 14-day treatment with regard to re-exacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.


  • Study population reflective of the type of patient we see
  • Randomised, blinded, placebo-controlled
  • Explanation for use of intravenous methylprednisolone provided (to facilitate administration of glucocorticoids to patients in distress)


  • Non inferiority trial – not powered to detect difference in treatment groups
  • Standard treatment (including antibiotics) for all COPD patients regardless of infective cause or degree of COPD severity (although trial population had higher rate of severe/very severe spectrum of COPD).
  • Only followed up for 6 months
  • 40 mg methylprednisolone is equivalent to 50mg prednisolone but further titration would have proved difficult

The Bottom Line

  • It has always been my practice to prescribe short courses of steroids in COPD exacerbations and this study reinforces it.


Summary author: @avkwong
Summary date: 12th August 2014
Peer-review editor: @stevemathieu75

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