The NICE clinical guideline on COPD (CG101; June 2010) recommends that oral corticosteroids be used, in conjunction with other therapies, in all patients admitted to hospital with an exacerbation of COPD, and be considered in patients in the community who have an exacerbation with a significant increase in breathlessness which interferes with daily activities. The recommended steroid regimen is prednisolone 30mg daily for 7-14 days.
Although glucocorticoid therapy has been shown in randomised trials to reduce length of hospital stay and accelerate recovery of FEV1, the optimal dose and duration are unknown. The purpose of the current study (REDUCE) was to see if a short-term course of prednisolone (5 days) is non-inferior to a conventional 14-day course in terms of clinical outcome, and if it would reduce the incidence of side-effects.
The study involved five hospitals and a total of 314 adults (311 in the intention-to-treat population) who presented to the emergency department with an acute COPD exacerbation. They were randomised to 40mg prednisolone daily for five days or 14 days, in addition to other standard treatments. The primary endpoint was time to next COPD exacerbation during a follow-up of 6 months – this did not differ between the groups (hazard ratio [HR] of re-exacerbation of 0.95; 90% CI 0.70 to 1.29; P=0.006) in the intention-to-treat group, meeting the non-inferiority criterion). There were also no differences seen for a number of lung function and disease-related symptom endpoints studied.
The short-course group had a statistically significantly shorter duration of hospital stay but this finding could not be readily explained due to the lack of any other differences (and may be a chance finding). The authors of a related editorial do however suggest that this may have been due to accelerated patient recovery in the short course group, and a possibly reduced risk of adverse events that were not reported (e.g. fluid retention; electrolyte imbalance).
Although the mean cumulative steroid dose was lower in the short-course group, there were no differences in rates of new or worsened hypertension or hyperglycaemia, infection rates, or other potentially glucocorticoid-associated adverse effects such as gastrointestinal bleeding, insomnia, fractures, psychiatric symptoms, or heart failure.
The authors acknowledge the limitations of their study, including the following:
• There was no standard glucocorticoid regimen when the study was started
• Some of the patients may have been over-treated (all were treated with inhaled, long-acting β-agonists, glucocorticoids, and tiotropium throughout the study period), which could explain the lower than expected exacerbation rates
• The length of hospital stay was insufficient to detect significant differences in blood pressure and blood glucose levels between groups
• All patients received antibiotics regardless of sputum purulence or procalcitonin levels, and this may not have always complied with current guidelines
• The results cannot necessarily be applied to patients with less severe COPD
• All patients were current or past smokers
The authors conclude that their findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.