Association of Corticosteroid Dose and Route of Administration With Risk of Treatment Failure in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

CONTEXT: Systemic corticosteroids are beneficial for patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (COPD); however, their optimal dose and route of administration are uncertain. OBJECTIVE: To compare the outcomes of patients treated with low doses of steroids administered orally to those treated with higher doses administered intravenously. DESIGN, SETTING, AND PATIENTS: A pharmacoepidemiological cohort study conducted at 414 US hospitals involving patients admitted with acute exacerbation of COPD in 2006 and 2007 to a non-intensive care setting and who received systemic corticosteroids during the first 2 hospital days. MAIN OUTCOME MEASURES: A composite measure of treatment failure, defined as the initiation of mechanical ventilation after the second hospital day, inpatient mortality, or readmission for acute exacerbation of COPD within 30 days of discharge. Length of stay and hospital costs. RESULTS: Of 79,985 patients, 73,765 (92%) were initially treated with intravenous steroids, whereas 6220 (8%) received oral treatment. We found that 1.4% (95% confidence interval CI, 1.3%-1.5%) of the intravenously and 1.0% (95% CI, 0.7%-1.2%) of the orally treated patients died during hospitalization, whereas 10.9% (95% CI, 10.7%-11.1%) of the intravenously and 10.3% (95% CI, 9.5%-11.0%) of the orally treated patients experienced the composite outcome. After multivariable adjustment, including the propensity for oral treatment, the risk of treatment failure among patients treated orally was not worse than for those treated intravenously (odds ratio OR, 0.93; 95% CI, 0.84-1.02). In a propensity-matched analysis, the risk of treatment failure was significantly lower among orally treated patients (OR, 0.84; 95% CI, 0.75-0.95), as was length of stay and cost. Using an adaptation of the instrumental variable approach, increased rate of treatment with oral steroids was not associated with a change in the risk of treatment failure (OR for each 10% increase in hospital use of oral steroids, 1.00; 95% CI, 0.97-1.03). A total of 1356 (22%) patients initially treated with oral steroids were switched to intravenous therapy later in the hospitalization. CONCLUSION: Among patients hospitalized for acute exacerbation of COPD low-dose steroids administered orally are not associated with worse outcomes than high-dose intravenous therapy.