Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of COPD

Christine Ma, Faculty of Medicine, University of New South Wales, Sydney Australia
doi:10.7244/cmj.2013.07.002

Three hundred and fourteen patients >40 years old with >20 pack year history and diagnosed acute exacerbation of COPD in hospital were randomised to have either 5 or 14 days of systemic glucocorticoids. The primary end point of this study was the time to next exacerbation over a follow-up period of 6 months, and secondary end points examined all-cause mortality, changes in pulmonary function testing, clinical performance, glucocorticoid-associated adverse events. Apart from a higher cumulative glucocorticoid exposure in the 14 day therapy group, there were no statistical differences in primary or secondary outcome measures between the two groups. The higher cumulative dose was also not associated with more adverse effects [4].Chronic obstructive pulmonary disease (COPD) is a common respiratory condition with a high level of resource utilisation through hospital admissions, specialist visits and chronicity of disease [1]. The WHO defines an exacerbation as an acute increase in symptoms beyond the normal daily variation, especially with an increase in cardinal symptoms of cough, sputum production and dyspnoea [2]. Current international guidelines advocate glucocorticoid use in acute exacerbations, with a 10-14 day course of oral prednisolone commonly utilised [3]. However the optimal dose and duration of treatment is unknown, and this placebo blinded RCT aimed to contribute to the body of literature in this area.

Long-term systemic glucocorticoid use is associated with a large number of adverse effects, and given the frequency of exacerbations, strategies limiting glucocorticoid exposure are welcome [5]. Given that the 5-day treatment with systemic glucocorticoids is not inferior clinically to a 14 day dose, and significantly decreased drug exposure, the shortened regimen may be preferable. This study looked at exacerbations requiring hospitalisation only, and future studies may investigate the effects on a less acutely unwell population with community-managed exacerbation, or a population over a longer period of follow-up. This may delineate whether the non-significant clinical effects are due to intensive hospital care, or perhaps too short a follow-up time frame.

References: 

1. Buist AS, McBurnie MA, Vollmer WM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet 2007; 370:741. doi: 10.1016/S0140-6736(07)61377-4
2. Global strategy for the diagnosis, management, and prevention of COPD: Revised 2011. Global initiative for Chronic obstructive lung disease (GOLD). file://www.goldcopd.org (Accessed on April 30, 2012).
3. Wouters EF. Management of severe COPD. Lancet. 2004; 364(9437):883-895. doi: 10.1016/S0140-6736(04)16984-5 
4. Leuppi JD, Schuetz P, Bingisser R, Bodmer M, et al; Short-term vs ConventionalGlucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. JAMA 2013; 309 (21):doi:10.1001/jama.2013.5023
5. Niewoehner DE, Erbland ML, Deupree RH, et al; Department of Veterans Affairs Cooperative Study Group. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1999; 340(25):1941-1947. doi:10.1056/NEJM19990624340250