Title: Steroids for Acute Exacerbation of Chronic Obstructive Pulmonary Disease – Five days is enough
Contributor Citation Information (Name, Degrees, Affiliation, AND EMAIL)
Author: Gary N. Asher, MD, MPH
Department of Family Medicine, University of North Carolina
gasher@med.unc.edu
Co-Author: Anne Mounsey MD. University of North Carolina at Chapel Hill.
(anne_mounsey@med.unc.edu)
Editor: James J. Stevermer, MD, MSPH (stevermerj@health.missouri.edu)
Department of Family and Community Medicine
University of Missouri - Columbia
Practice Changer
Five-day steroid treatment works as well as 14-day treatment for acute COPD exacerbation. (SOR B:
Based on a single, well done, RCT)
Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute
exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA.
2013;309(21):2223-2231.1
Illustrative Case
A 55-year-old man with COPD presents to the Emergency Department because of progressive shortness
of breath, cough, and sputum production over the past 4 days. He is diagnosed with a COPD
exacerbation, treated with corticosteroids, and admitted to the inpatient service. His hospital treatment
includes antibiotics, inhaled albuterol and atrovent, supplemental oxygen, and oral corticosteroids.
How many days of oral steroids should he be given?
Clinical Context
Severe exacerbations of COPD are independently associated with mortality regardless of baseline COPD
severity.2 Furthermore, nearly 60% of the cost of the disease is associated with acute exacerbations,
particularly those episodes requiring hospitalization.3 Guidelines and systematic reviews advise use of
oral glucocorticoids in the management of acute COPD exacerbation because they shorten recovery
time and length of hospital stay, improve lung function, and reduce the risk of early relapse and
treatment failure.4-6 However, it is unknown how long the steroid course should be. Data supporting a
14-day course compared to longer duration comes from the Systematic Corticosteroids in COPD
Exacerbations (SCCOPE) trial.7 The current GOLD criteria suggest a dose of 30-40 mg daily for 10-14 days,
but the report recognizes there are insufficient data from clinical and observational studies to support
this recommendation.4 A recent Cochrane review compared short course treatment (3-7 days) to longer
duration treatment (10-15 days) and judged the current evidence as inconclusive to recommend a
clinical practice change.6
The REDUCE study is a double-blinded, randomized, controlled trial that compared the use of 5-day
verses 14-day oral steroid treatment in patients hospitalized for acute COPD exacerbation.1
Study Summary
Five-day steroid treatment (40 mg) may be sufficient for most patients with acute COPD exacerbations.
The REDUCE study used a non-inferiority methodology to compare 5 versus 14 day courses of
prednisone (40 mg daily) in treating patients with COPD exacerbations. A patient was considered to
have a COPD exacerbation if he or she had a change from baseline in at least 2 of the following:
dyspnea, cough, sputum quantity or purulence. Participants were consecutive patients who presented
to the Emergency Department at 1 of 5 Swiss teaching hospitals between March 2006 and February
2011. They were eligible if they were 40 years or older and had at least 20 pack-years of smoking. The
investigators excluded patients with asthma, mild obstruction (FEV1:FVC > 70%), pneumonia, an
estimated survival less than 6 months, pregnancy or lactation. All patients (n=311) received 40 mg
methylprednisolone IV on day 1, and then prednisone 40 mg orally on each of days 2 through 5. The
researchers then randomly allocated participants into 2 groups and treated one group with prednisone
40mg daily and the other with matching placebo for a further 11 days. Participants also received seven
days of antibiotics, twice daily inhaled steroids, daily tiotropium, and nebulized albuterol as needed.
The primary outcome was the time to next COPD exacerbation (up to 180 days). Non-inferiority
between the groups was defined as no more than a 15% absolute increase in exacerbations. The
dropout rate was 5.7% and evenly divided between groups. Intention-to-treat and per-protocol
analyses were conducted, and hazard ratios were calculated using the Kaplan-Meier method and Cox
proportional hazard models.
The time to next COPD exacerbation did not differ between the study groups (HR 0.95, 90% CI: 0.70 –
1.29). Sensitivity analyses adjusting for baseline characteristics provided similar results as did the perprotocol analysis. Secondary outcomes (overall survival, need for mechanical ventilation, need for
additional corticosteroids, and clinical performance measures, such as dyspnea score and quality of life)
also did not differ between groups. There were no between-group differences for hyperglycemia,
worsening hypertension, infection, or other adverse effects typically associated with glucocorticoid use.
The active treatment group took over 400 mg more prednisone than the placebo group (mean 793 mg
vs. 379 mg; p<0.001).
What’s New
While randomized trials demonstrate glucocorticoids improve COPD symptoms we don’t know the best
treatment dose or duration. All current guidelines recommend treatment for longer than 5 days. This
trial clearly demonstrated that 40 mg of prednisone for 5 days is at least as good as a 14-day treatment
course. Furthermore, it is unnecessary to taper the short-course therapy, simplifying the treatment
regimen.
Caveats
More than 80% of patients with acute COPD exacerbation can be managed in the outpatient setting.4
However, participants in this trial were hospitalized for a median of 8.5 days and most had severe or
very severe COPD, which doesn’t fully represent the typical COPD population seen in outpatient
practice. Fortunately, patients with less severe disease are probably at least as likely to respond to short
course steroids as those with more severe disease. Importantly, participants in this study all received
optimal guideline-based therapies during hospitalization, which may be difficult to achieve for some
patients treated in the outpatient setting. Finally, treatment adherence observed during the
hospitalization period in this trial is unlikely to be replicated in the outpatient setting.
Challenges to Implementation
For patients with new COPD exacerbation, or those successfully treated using short course treatment in
the past, a 5-day regimen may be appropriate. For patients who have failed prior attempts at short
course treatment, a 14-day regimen may be more advisable. However, there is no guideline to help
choose which patients previously treated with longer course regimens may fail on short-course
regimens.
Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the
National Center For Research Resources, a Clinical Translational Science Award to the University of
Chicago. The content is solely the responsibility of the authors and does not necessarily represent the
official views of the National Center For Research Resources or the National Institutes of Health.
References
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7.
Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in
acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical
trial. JAMA. Jun 5 2013;309(21):2223-2231.
Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R.
Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary
disease. Thorax. Nov 2005;60(11):925-931.
Hilleman DE, Dewan N, Malesker M, Friedman M. Pharmacoeconomic evaluation of COPD.
Chest. Nov 2000;118(5):1278-1285.
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for Diagnosis,
Management, and Prevention of COPD (Updated 2013). Available online at www.goldcopd.org
Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a
systematic review and metaanalysis. Chest. Mar 2008;133(3):756-766.
Walters JA, Wang W, Morley C, Soltani A, Wood-Baker R. Different durations of corticosteroid
therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst
Rev. 2011(10):CD006897.
Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on
exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs
Cooperative Study Group. N Engl J Med. Jun 24 1999;340(25):1941-1947.