Failure of Low-Dose Theophylline to Prevent Exacerbations in Patients With COPD

Abstract

Exacerbations drive morbidity, mortality, and the costs of care in patients with chronic obstructive pulmonary disease (COPD). Inhaled therapy with long-acting bronchodilators, with or without inhaled glucocorticoids, can help prevent further exacerbations, but some patients continue to experience them despite optimal inhaled medical therapy. These patients are most prone to hospitalization and death with limited pharmacological alternatives to decrease future exacerbations. Long-term macrolide therapy and phosphodiesterase type 4 inhibitors may be options for some patients with recurrent exacerbations, but use of these agents can be cost prohibitive, or cannot be tolerated by all patients. This population represents a large clinical unmet need that requires additional therapeutic options.Theophylline has been used as a bronchodilator for close to 9 decades. A bronchodilator response occurs above plasma concentrations of 10 mg/L, but higher concentrations are associated with increased toxicity. This narrow therapeutic window has restricted current guideline recommendations to use theophylline only as a fourth-line agent in patients who are refractory to more potent and better-tolerated inhaled bronchodilators. 1,2