Patients with COPD experience exacerbations approximately 1 to 2 times per
year; those with frequent episodes are reported to have a more rapid decline in overall lung
function. Exacerbations are triggered by a number of factors
(i.e., exposure to pollutants and interruption of maintenance therapy), but the majority of episodes
are caused by bacterial and viral respiratory tract infections.1
Standard therapy for the treatment of COPD exacerbations is directed towards
minimizing the impact of the current episode and preventing future occurrences. The Global Initiative for Obstructive Lung Disease (GOLD)
treatment guidelines recommend a 10-14 day course of systemic glucocorticoid therapy, a
recommendation which is based on a trial published
In recent years, experts have questioned whether 10-14 days increases risk of side effects
and mortality, while failing to provide additional therapeutic benefit.2,3
The REDUCE Trial was designed to
investigate whether a 5-day course was non-inferior to a 14-day course of systemic glucocorticoids
for the treatment of COPD exacerbations. A total of 314
patients, presenting to the emergency department with an exacerbation, were randomized to either a
conventional therapy group or a short-term therapy group.
The inclusion criteria were defined as at least 2 of the following: 1) change in baseline
dyspnea, cough or sputum quantity or purulence 2) age > 40, or 3) smoking history of ≥ 20
pack years. Patients with a history of asthma,
FEV1/FEV > 70% prior to
randomization, and presence of pneumonia were excluded from the study. Eligible patients were
stratified based on age, previous glucocorticoids use,
severity of disease and trial site.3
Patients in the short-term group
received corticosteroids for 5 days and a placebo for the remaining 9 days, whereas the
conventional group received a full 14-day course of therapy. The first dose was given IV (40 mg
methylprednisolone) to facilitate administration to patients in distress; subsequent doses were
given orally (40 mg prednisone). All patients also received a broad-spectrum antibiotic for 7 days
and nebulized short-acting bronchodilators 4-6 times/day while hospitalized.
The primary end point was time to
re-exacerbation within 180 days of treatment. Secondary outcomes included all-cause mortality,
length of hospital stay, and change in FEV1.
Glucocorticoid-associated adverse effects, such as new or worsening hyperglycemia,
hypertension, and/or infection were recorded. End points and adverse effects were assessed daily
during hospitalization then again on days 6, 15, 30, 90, and 180.3
Results indicated that the primary
endpoint was reached by 35.9% of patients in the short-term group as compared to 36.8% in the
conventional group (p=0.006). In terms of secondary
outcomes, no significant difference in mortality was observed among the two groups. A significant improvement in
FEV1 from baseline was seen with both
treatment groups (p<0.001) and remained stable throughout the follow up period. Those in the short-term treatment group had shorter hospital
stays (p=0.04) as compared to the conventional group. While
the short-term group displayed a slightly more favorable glucocorticoid-associated adverse effect
profile, the difference in cases of new or worsening hyperglycemia, hypertension, and infection
were statistically insignificant (p>0.99).3
A 5-day course of glucocorticoids
was found to be non-inferior to a 14-day course in treating patients requiring hospitalization for
acute COPD exacerbations. The study design aimed to limit
the risk of confounding by administering antibiotics to all patients as well as nebulized
short-acting bronchodilators 4-6 times per day while hospitalized. However, it
is difficult to determine the influence these medications had on the final results.3
The results of this particular
trial, which implemented sound non-inferiority criteria and
utilized appropriate dosing, support the decision by practitioners to opt for a shorter duration of
systemic steroid therapy when treating acute COPD exacerbations.
The practice could limit cumulative exposure to glucocorticoids and the numerous adverse
effects related to their long-term use.
1. Soler-Caraluna JJ,
Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations
and mortality in patiends with chronic obstructive pulmonary disease. Thorax.
2. Global Initiative for
Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of
COPD. http://www.goldcopd.org/guidelines/guidelines-resources.html. Accessed September 13,
3. Leuppi JD, et al.
Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive
pulmonary disease: the REDUCE Randomized Clinical Trial. JAMA 2012; 309(21):2223-2231.