Abstract & Commentary
Source: Aaron SD, et al. Outpatient oral prednisone for emergency treatment of chronic obstructive pulmonary disease. N Engl J Med 2003;348:2618-2625.
This prospective randomized, double-blind, placebo-controlled trial from Ian Stiell’s group looked at the use of prednisone 40 mg daily for 10 days vs. placebo in 147 patients presenting to any of 10 emergency departments (EDs) who were well enough to be discharged after treatment for exacerbation of their chronic obstructive pulmonary disease (COPD). Exacerbation was defined as a recent increase in at least two of the following three criteria: breathlessness, sputum volume, or sputum purulence. Definitions of COPD were reasonably stringent, and an effort was made to exclude asthmatics. Other exclusion criteria centered on coexistent disease (active pneumonia or congestive heart failure; uncontrolled diabetes mellitus; or liver/kidney failure) or recent use of oral/intravenous steroids (prior 30 days). Patients were randomized at discharge from the ED, and also were given a 10-day course of oral antibiotics, as well as 30 days of therapy with inhaled albuterol and ipratropium bromide with spacers. Inhaled steroids were continued at discharge if they were part of the patient’s medical regimen at the time of enrollment; both groups were equivalent in the use of these agents.
The main outcome measure was the relapse rate at 30 days, and this was rigorously verified. The prednisone group had a significantly lower relapse rate than did the placebo group (27% vs 43% for placebo, P = 0.05; relative risk of 30-day relapse after prednisone therapy 0.63 [95%CI: 0.40-1.01]). Time to relapse for 25% of the patients also was delayed significantly in the prednisone group (23 days vs seven days in the placebo group, P =0.04). At 10 days, the prednisone group showed significant improvement in lung function (forced expiratory volume in one second) and subjective dyspnea scores.
There was no difference between groups, however, in health-related quality-of-life scores; the authors linked this to significant increases in appetite (46% vs 22%, P = 0.003), weight gain (13% vs 1%, P = 0.01) and insomnia (48% vs 21%, P = 0.001), as well as nonsignificant trends toward a higher rate of depression and anxiety, in the prednisone group. The authors concluded that 10 days of prednisone therapy in patients discharged from the ED with exacerbations of COPD reduces the risk of relapse at 30 days, and offers a small advantage over placebo.
Comment by Richard A. Harrigan, MD
This well-designed trial offers guidance as to how to use oral steroids in patients we are discharging from the ED after treatment for their COPD exacerbation. A 10-day "burst" of prednisone without taper offered improvement in subjective and objective indices of lung function, and a decreased relapse rate. Other studies have shown improvement in disease with prolonged (two weeks as good as eight weeks) steroid therapy with taper vs. placebo, when begun in the inpatient setting.1
Hyperglycemia requiring treatment was found to be a significant downside of steroid therapy in one study, with a 15% rate in the steroid group vs. a 4% rate in the placebo (p = 0.02).1 This study by Aaron and colleagues did not specifically look at hyperglycemia; two patients with diabetes in each group reported high blood sugars, but the incidence of unreported hyperglycemia was unknown. The lack of improvement in health-related quality of life suggests we should warn our patients discharged on prednisone about not only the benefits, but the risks2; specifically those identified in this study—that they may experience an increase in appetite, weight gain, and difficulty sleeping. It also would be prudent to warn patients—especially diabetics—about the possibility of hyperglycemia.
Dr. Harrigan, Associate Professor of Emergency Medicine, Temple University Hospital and School of Medicine, Philadelphia, PA, is Editor of Emergency Medicine Alert.
1. Niewoehner DE, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1999;340:1941-1947.
2. Irwin SR, et al. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 2003;348:2679-2681.