A related commentary discusses this research. Despite the limited ability of theophylline to improve patient outcomes without significant adverse effects, a 2008 study reported that theophylline was used in up to 35% of patients with COPD. Although some studies have shown an improvement with theophylline when added to formoterol compared with placebo, or compared with placebo alone, no study has shown that theophylline can reduce exacerbation rates as add-on therapy to optimal therapy with inhaled corticosteroids. Based on the results of this study it appears that theophylline has no current role as add-on therapy to prevent future exacerbations for patients already treated with combination long-acting bronchodilator and inhaled corticosteroid therapy. It is somewhat disappointing that low-dose theophylline did not result in a reduction in exacerbation risk because the drug is relatively inexpensive, and its rationale was based on sound preclinical and human mechanistic studies.