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Dose dependent increased mortality risk in COPD patients treated with oral glucocorticoids

Depts of ¹ Pulmonology and ² Methodology and Statistics and ³ Epidemiology, Maastricht University, Maastrich and ⁴ Asthma Centre Hornerheide, Horn, the Netherlands

CORRESPONDENCE: A.M.W.J. Schols, Dept of Pulmonology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht. Fax: 31 433875051

Keywords: chronic obstructive pulmonary disease, corticosteroids, survival, systemic administration

Received: February 16, 2000
Accepted October 24, 2000

Systemic corticosteroids are often administered in COPD patients. The relationship between systemic glucocorticoids and mortality in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was retrospectively analysed. Baseline characteristics of the patients, in stable clinical condition, were collected on admission to a pulmonary rehabilitation centre. Overall mortality was asessed at the end of follow-up. The Cox proportional hazards model was used to quantify the relationship between glucocorticoid use, distinguishing administration route (oral/inhalation) and oral dose, and overall mortality, adjusted for the influence of age, sex, smoking, lung function, resting arterial blood gases and body mass index.

On multivariate analysis, oral glucocorticoid use at a (prednisone equivalent) dose of 10 mg·day^–1 without inhaled glucocorticoids, was associated with an increased risk (RR=2.34, 95% confidence interval (CI) 1.24–4.44) while 15 mg·day^–1 carried a relative risk of 4.03, CI=1.99–8.15). A significant interaction was observed between inhaled and oral glucocorticoid use. Combined with inhaled glucocorticoids, the relative risk of oral glucocorticoid use appeared to be significantly smaller.

It is concluded that in severe chronic obstructive pulmonary disease, maintenance treatment with oral glucocorticoids is associated with increased mortality in a dose-dependent manner. Since the present study design cannot exclude the possibility of bias by indication, further prospective studies are indicated using a broader patient characterization.