Patients with chronic obstructive pulmonary disease (COPD) frequently require hospitalization or intensive outpatient treatment when their symptoms worsen. Standard therapies for COPD include bronchodilators, oxygen, antibiotics and systemic steroids. In patients admitted to the hospital, high doses of steroids are often used, despite equivocal proof of efficacy in this clinical situation. Conversely, the adverse effects of steroids—hyperglycemia, mood changes and secondary infections—are well-known. Niewoehner and colleagues performed a randomized, double-blind, placebo-controlled trial to assess the role of systemic steroids in the management of exacerbations of COPD. The two goals of the study were to determine the rates of treatment failure and determine the optimal duration of steroid therapy.
Patients enrolled were men 50 years of age and older who were admitted to the hospital with a diagnosis of exacerbation of COPD. All patients had a smoking history of at least 30-pack years and a forced expiratory volume in one second (FEV1) of 1.5 L or less. Patients were excluded if they had asthma or had received systemic steroids within 30 days.
Patients were randomized into one of three treatment groups. The first group was given 125 mg of intravenous methylprednisolone every six hours for 72 hours followed by oral prednisone that was tapered from 60 to 5 mg daily over an eight-week period. The second group received the same dosage of methyl-prednisolone followed by a tapering dose of oral prednisone (60 mg down to 20 mg) for a two-week period. The third group received intravenous dextrose followed by oral placebo tablets for eight weeks. All patients received seven days of a broad-spectrum antibiotic and were maintained on inhaled betaagonist, ipratropium bromide and triamcinolone acetonide for the six-month follow-up period.
Treatment failure was defined as death from any cause, need for intubation, need for readmission or intensification of pharmacologic therapy. Regular evaluations were carried out while in the hospital, followed by outpatient evaluations including spirometry at two weeks, eight weeks and six months.
Initially, 1,840 men were screened, of whom 271 were determined to be eligible. The average age was 67 years, and approximately 83 percent were white. Other baseline characteristics of the three groups were essentially the same. Compared with the placebo group, the rates of treatment failure were significantly lower in the steroid groups at 30 days (23 versus 33 percent) and at 90 days (37 versus 48 percent).
Patients who received eight weeks of steroids did not fare any better than those who received only two weeks. In addition, by six months the rates of treatment failure in the placebo and steroid groups were almost the same (51 versus 54 percent). Patients who received steroids did have shorter hospital stays (8.5 versus 9.7 days) and had a faster improvement in FEV1. By the end of two weeks, there were no significant differences in FEV1 between placebo and steroid patients.
The most significant difference in terms of complications was hyperglycemia requiring treatment, which occurred in 15 percent of the steroid group but in only 4 percent of the placebo group. There were no significant differences in rates of infection, hypertension or psychiatric disorders. Seven deaths in the placebo group and six deaths in the steroid group were attributed to COPD.
The authors conclude that systemic steroids provide a mild benefit for the treatment of exacerbations of COPD. The effect persists for at least 90 days. There appears to be no benefit to administering steroids for longer than two weeks; an eight-week regimen was no more effective than a two-week regimen. It is unclear whether this benefit can be applied to the treatment of patients with mild exacerbations or stable COPD.
editor's note: This study should challenge physicians to reevaluate their management approach to COPD, especially the use of steroids. At best, a short course of steroids may be indicated for select patients and must be weighed against the adverse effects of these medications. Similar data have been found with inhaled steroids in patients with COPD; that is, the benefits are small, often of short duration, and do not affect the clinical course of the disease.—j.t.k.