Elsevier

The Lancet

Volume 354, Issue 9177, 7 August 1999, Pages 456-460
The Lancet

Articles
Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial

https://doi.org/10.1016/S0140-6736(98)11326-0Get rights and content

Summary

Background

The role of oral corticosteroids in treating patients with exacerbations of chronic obstructive pulmonary disease (COPD) remains contentious. We assessed in a prospective, randomised, double-blind, placebo-controlled trial the effects of oral corticosteroid therapy in patients with exacerbations of COPD requiring hospital admission.

Methods

We recruited patients with non-acidotic exacerbations of COPD who were randomly assigned oral prednisolone 30 mg once daily (n=29) or identical placebo (n=27) for 14 days, in addition to standard treatment with nebulised bronchodilators, antibiotics, and oxygen. We did spirometry and recorded symptom scores daily in inpatients. Time to discharge and withdrawals were noted in each group. We recalled patients at 6 weeks to repeat spirometry and collect data on subsequent exacerbations and treatment. Hospital stay was analysed by intention to treat and forced expiratory volume in 1 s (FEV1) according to protocol.

Findings

FEV1 after bronchodilation increased more rapidly and to a greater extent in the corticosteroid-treated group: percentage predicted FEV1 after bronchodilation rose from 25·7% (95% CI 21·0-30·4) to 32·2% (27·3-27·1) in the placebo group (p<0·0001) compared with 28·2% (23·5-32·9) to 41·5% (35·8-47·2) in the corticosteroidtreated group (p<0·0001). Up to day 5 of hospital stay, FEV1 after bronchodilation increased by 90 mL daily (50·8-129·2) and by 30 mL daily (10·4-49·6) in the placebo group (p=0·039). Hospital stays were shorter in the corticosteroidtreated group. Groups did not differ at 6-week follow-up.

Interpretation

These data provide evidence to support the current practice of prescribing low-dose oral corticosteroids to all patients with non-acidotic exacerbations of COPD requiring hospital admission.

Introduction

Chronic obstructive pulmonary disease (COPD) is an important cause of death worldwide and exacerbations of this disease commonly lead to hospital admission (1250 per year in our 350 000 health district) and increased cost. The treatment of exacerbations of COPD is controversial. Guidelines1, 2 have made recommen-dations about prescribing, but although there are clear indications for antibiotic and bronchodilator use, they state that the use of oral corticosteroids is based on common practice and is not evidence based.

When given to stable COPD patients, systemic corticosteroids significantly increase the forced expiratory volume in 1 s (FEV1) in only 10% of cases,3 whereas inflammatory-mediator production is not influenced by this treatment.4 Moreover, continued use of oral corticosteroids in COPD patients is associated with corticosteroid myopathy,5 which may be potentially important for patients with frequent exacerbations who are treated with these drugs.

Several studies have investigated the outcome of systemic use of corticosteroids in exacerbations of COPD with conflicting results. One study of 96 patients suggested that there was no effect of methylprednisolone in preventing admission to hospital after 5 h treatment in the emergency room,6 although a later, randomised double-blind study found that the readmission rate was lower in patients given treatment.7 In a randomised controlled trial, Albert and colleagues8 noted significant improvements in FEV1 before bronchodilation in the first 3 days of admission in 22 patients given intravenous methylprednisolone, but improvements in FEV1 after bronchodilation were less obvious. In another randomised controlled trial, 27 patients fit enough for discharge from the emergency room were followed up.9 The 13 treated patients showed greater improvement in FEV1 and the partial pressure of oxygen in arterial blood than did the 14 untreated patients. The Veterans Affairs Cooperative study group has completed a study of the effects of high-dose systemic corticosteroids on exacerbations of COPD.10 The primary endpoint was treatment failure, rates of which were significantly lower in the glucocorticoid-treated groups than in the placebo group.

Most COPD patients admitted with exacerbations in the UK, New Zealand, and Australia11, 12, 13 are treated with 30–40 mg oral prednisolone. We investigated the hypothesis in a prospective, randomised, double-blind, placebo-controlled trial that in more severe patients, oral corticosteroids administered in these doses would not modify the rate of improvement of lung function or significantly affect the course of hospital stay.

Section snippets

Patients

Patients with a diagnosis of COPD presenting to the accident and emergency department of University Hospital Aintree, Liverpool, were eligible for entry into the study if they had a history of increased breathlessness and at least two of the following symptoms for 24 h or more: increased cough frequency or severity, increased sputum volume or purulence, and increased wheeze. We included patients who were aged 40–80 years, had a history of at least 20 pack-years of cigarette smoking, and had

Results

We screened 246 patients for the study, and 60 met the inclusion criteria (figure 1). The most common reason for exclusion was previous treatment with oral corticosteroids before attending the accident and emergency department. Of the four patients refusing consent, three declined because they refused oral corticosteroids after being told of possible side-effects and one because she did not wish to participate in a clinical trial.

29 patients were randomly assigned active treatment and 27 were

Discussion

Any treatment that can hasten the resolution and lower the costs of exacerbations of COPD17, 18 is welcomed. Data from randomised trials in outpatients suggest that oral corticosteroids can increase the rate of resolution of the attack, but data have only been seen in short-term treatment of inpatients and the impact on health costs was unclear. We found significant differences in the rate of improvement of FEV1 before and after bronchodilation compared with placebo, which suggests that the

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