Correspondence
Glucocorticoids for Chronic Obstructive Pulmonary Disease
N Engl J Med 1999; 341:1772-1773December 2, 1999
- Article
To the Editor:
Niewoehner et al. (June 24 issue)1 reported the effects of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease (COPD). They designed their study to evaluate clinical outcomes and found that patients treated with systemic glucocorticoids had a shorter initial hospital stay (8.5 days) than patients who received placebo (9.7 days). They also found, however, that the glucocorticoid-treated patients spent more time in the hospital for reasons other than COPD during the six-month period after their initial hospitalization. With the initial hospital stay added to subsequent stays, the patients in the glucocorticoid group spent about two more days in the hospital than those in the placebo group. This two-day difference is clinically important and may be statistically significant. The authors did not report the statistical significance of this difference. Thus, it may be fair to conclude on the basis of their findings that patients who receive high-dose glucocorticoid therapy for acute exacerbations of COPD may be likely to require a greater number of days in the hospital than patients who do not receive this therapy.
A potential explanation for the excessively high rate of complications in the study may be related to the high dose of glucocorticoids used. In the two groups receiving glucocorticoids — one group for eight weeks and one group for two weeks — the patients received 125 mg of intravenous methylprednisolone every 6 hours for 72 hours, followed by once-daily oral prednisone. The initial dose of prednisone was 60 mg, and the dose was then tapered according to the protocol for the regimen (eight-week course or two-week course) to which the patient was assigned. In standard clinical practice, however, the usual dose of methylprednisolone for exacerbations of COPD is approximately 0.5 mg per kilogram of body weight every 6 to 12 hours. This lower dose has been used in other studies of methylprednisolone in patients with exacerbations of COPD.2 Many of the adverse reactions to systemic glucocorticoids are dose-related, especially hyperglycemia and immunosuppression.3 In the study by Niewoehner et al., immunosuppression was responsible for the higher rate of secondary infection in the group of patients receiving glucocorticoids for eight weeks than in the group receiving glucocorticoids for two weeks or the placebo group. It is important to study the effect of lower doses of methylprednisolone for the treatment of COPD exacerbations, in order to determine whether they have the same initial clinical effect as higher doses but involve fewer long-term complications.
3 ReferencesSandeep Kapur, M.D.
Yizhak Kupfer, M.D.
Sidney Tessler, M.D.
Maimonides Medical Center, Brooklyn, NY 112191
Niewoehner 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
Full Text | Web of Science | Medline2
Albert RK ,Martin TR ,Lewis SW . Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. Ann Intern Med 1980;92:753-758
Web of Science | Medline3
McEvoy CE ,Niewoehner DE . Adverse effects of corticosteroid therapy for COPD: a critical review. Chest 1997;111:732-743
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: It is entirely possible that a lower dose of systemic glucocorticoids might have the same beneficial effect as the dose we used, with fewer adverse effects, but another clinical trial, probably much larger than the one we performed, would be required to prove the point. There are no reliable data on the best dose of glucocorticoids for treating acute asthma; the small studies that have been conducted have had unclear results. We are not aware of any controlled trials comparing different doses of glucocorticoids in patients with exacerbations of COPD, and the doses used in previous efficacy studies were, as far as we could determine, arbitrarily chosen. When planning our study, we chose the highest dose of glucocorticoids commonly used in clinical practice, because we did not want any post hoc criticism about inadequate doses if the trial had a negative result.
Although the initial hospital stay was shorter for the glucocorticoid-treated patients than for those who received placebo (8.5 vs. 9.7 days, P=0.03), the glucocorticoid-treated patients spent more time in the hospital during the follow-up period (6.3 vs. 3.2 days, P=0.17). For the entire 6-month period, the patients in the placebo group spent fewer days in the hospital, but the difference was not significant (12.9 days vs. 14.8 days, P=0.80). A relatively large number of pneumonias in the group of patients who received glucocorticoids for eight weeks accounted for much of the excess hospital days in the two glucocorticoid groups combined. The duration of glucocorticoid therapy may be as important as the dose in determining the risk of infection. These analyses are post hoc, so they cannot be given the same weight as outcomes specified in the study protocol. However, we recognize that there is some hazard in prescribing high doses of systemic glucocorticoids, and in our article, we tried to present a balanced picture of the benefits and risks.
Dennis E. Niewoehner, M.D.
Veterans Affairs Medical Center, Minneapolis, MN 55417Marcia Erbland, M.D.
Veterans Affairs Medical Center, Little Rock, AR 72205Dorothea Collins, Sc.D.
Veterans Affairs Cooperative Studies Program, Coordinating Center, West Haven, CT 06516
