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The Role of Corticosteroids in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

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Several effective medications are used to treat COPD exacerbation. Initially, all patients should be placed on oxygen. Other mainstay drugs in the treatment of COPD exacerbations include anticholinergic agents such as ipratroprium bromide and short-acting ß₂-agonists such as albuterol. Antibiotics are indicated if a bacterial infective cause is suspected.

The use of systemic intravenous or oral corticosteroids in COPD exacerbations has been debated in the past, but these drugs are now recommended as standard care in addition to bronchodilators. Steroids are effective for dramatically and rapidly inhibiting the inflammatory process in the lungs. The dose of steroids and the duration of therapy needed are under debate, but higher doses and long durations have not been shown to have any increased benefit in recent studies.²

One randomized trial showed significant improvement in the forced expiratory volume in 1 second (FEV₁) in patients receiving corticosteroid therapy. Patients were randomized to receive placebo or methylprednisolone 125 mg 4 times daily for 3 days, followed by an oral taper of prednisone for either 2 or 8 weeks. Both steroid groups showed initial improvement compared with the placebo group. This initial benefit of steroid treatment diminished over time and was not significant after 2 weeks. The length of stay in the hospital was shorter in steroid-treated patients compared with those treated with placebo. At early follow-up intervals, both steroid groups had decreased rates of treatment failure (death, intubation, readmission, or intensification of pharmacologic treatment), but no significant difference existed between treatment groups and placebo by 6 months. No difference in death rates was observed between any of the groups throughout this study. The only major difference in side effects of these treatment groups was a higher incidence of hyperglycemia and longer hospital stays for indications other than COPD (especially infection) in the steroid groups. This study showed that steroids are superior to placebo at quickly improving lung function and avoiding treatment failures. This study also demonstrated that an 8-week course of steroids was just as effective as a 2-week course for COPD exacerbation treatment, and the patients on an 8-week course had a greater incidence of side effects.⁵

Davies et al⁶ found that a much lower dose of steroid (oral prednisolone 30 mg daily) was also effective at improving FEV₁ and decreasing length of hospital stay compared with placebo. Patients demonstrated an increase in FEV₁ at day 3 of treatment with continued improvement at days 10 and 14. This study is the only published trial that has measured FEV₁ daily, and the researchers reported that improvement over placebo ceased after 5 days of treatment with no real difference from placebo at discharge or at 6 weeks follow-up.⁶ Another study showed that treatments lasting 5 days to 2 weeks are effective, whereas treatments of longer duration have shown no additional benefit.⁷

A study conducted by Sayiner et al⁸ demonstrated that 3 days of treatment for COPD exacerbation with methylprednisolone 0.5 mg/kg every 6 hours was not as effective as the same initial treatment followed by a methylprednisolone taper for a total treatment of 10 days. Patients in the 10-day treatment group had significant improvement in objective lung function tests, as well as significant symptomatic improvement compared with the 3-day treatment group. Optimal steroid treatments appear to last for 10 to 14 days.⁸ Unfortunately, quality studies that evaluate parenterally versus orally administered corticosteroids for COPD exacerbations are not available.

The Global Initiative for Chronic Obstructive Lung Diseases recommends corticosteroid treatment for COPD exacerbations with methylprednisolone 40 mg daily for 10 days.² Chronic or long-term use of steroids is not recommended, because steroids can lead to myopathy and related loss of pulmonary function, as well as many other adverse effects. Although studies support relatively short-course steroid regimens, some patients, especially those already steroid dependent, may require a longer duration of corticosteroid treatment to avoid a relapse of the exacerbation.² Clinical judgment is the most important factor when determining the duration of steroid treatment for individual patients.

Steroids have been shown to improve outcomes, such as short-term lung function and length of hospital stay, in COPD exacerbations. Evidence now supports lower doses of steroids than have traditionally been used for exacerbations. Relatively shorter durations in steroid therapy are also supported as being effective and safer than extended duration treatments.

References

1. Stoller JK. Clinical practice. Acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 2002;346:988–994.[Free Full Text]
2. Pauwels R, Anthonisen N, Bailey WC, et al. Executive summary global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO workshop report 2001. Available at: http://www.goldcopd.com/exec_summary/summary_2001.html. Accessed June 2002.
3. Sherk PA, Grossman RF. The chronic obstructive pulmonary disease exacerbation. Clin Chest Med. 2000;21:705–721.[Medline]
4. Breen D, Churches T, Hawker F, Torzillo PJ. Acute respiratory failure secondary to chronic obstructive pulmonary disease treated in the intensive care unit: a long term follow up study. Thorax. January 2002;57:29–33.[Abstract/Free Full Text]
5. Stanbrook MB, Goldstein RS. Steroids for acute exacerbations of COPD: how long is enough? Chest. 2001;119:675–676.[Free Full Text]
6. Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet. 1999;354:456–460.[Medline]
7. Nidwoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1999;340:1941–1947.
8. Sayiner A, Aytemur ZA, Cirit M, Unsal I. Systemic glucocorticoids in severe exacerbations of COPD. Chest. 2001;119:726–730.[Abstract/Free Full Text]

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