Adults with chronic obstructive pulmonary disease (COPD) who are at high risk for exacerbation and who are treated with both inhaled corticosteroids and low-dose theophylline as adjunct therapy had no fewer exacerbations than those not treated with theophylline, according to the results of a study published in the Journal of the American Medical Association. 

The number of patient-reported moderate or severe COPD exacerbations was compared in a pragmatic, double-blind, placebo-controlled, randomized clinical trial. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity of <0.7 with ≥2 exacerbations in the previous year and were being treated with an inhaled corticosteroid. Comparisons were made between those who received inhaled corticosteroids only (placebo) and those who received low-dose theophylline as adjunct therapy.

Of the 1536 participants in the study, 772 were randomly assigned to the theophylline group (200 mg once or twice per day) and 764 to the placebo group. There were 3420 exacerbations of COPD symptoms during the year-long study. Exacerbation rates for participants who received inhaled corticosteroids only and for those who received low-dose theophylline as adjunct therapy were not statistically different between the 2 groups. There were 772 exacerbations in the theophylline group and 764 exacerbations in the placebo group.

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Serious adverse events in patients in both groups included gastrointestinal (2.7% vs 1.3%) and cardiac (2.4% vs 3.4%) as well as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%), but the differences were not significant.The researchers noted the clinical relevance of this finding, suggesting, “The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations.”


Devereux G, Cotton S, Fielding S, et al. Effect of theophylline as adjunct to inhaled corticosteroids on exacerbations in patients with COPDJAMA. 2018;320(15):1548-1559.