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Mortality Risk in Chronic Obstructive Pulmonary Disease Patients Using Theophylline

Research Report Dec 4, 2009
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To evaluate the comparative effectiveness of treatment regimens with theophylline compared to the regimen without theophylline.


Retrospective cohort study


United States Veterans Affairs healthcare system from October 2001 through September 2005.


Patients with a diagnosis of chronic obstructive pulmonary disease that were 45 years or older

Measurements adn Main Results

Primary outcome measures were all-cause mortality, chronic obstructive pulmonary disease exacerbations and chronic obstructive pulmonary disease-related hospitalizations. Two approaches were used, the first where treatment assignment was based on medication use at baseline, and the second where exposure was measured as a time-varying covariate. Treatment groups were stratified based on propensity to receive theophylline. Mortality was compared using Cox proportional hazards models and other outcomes were compared using negative binomial models. Comparisons were conducted within individual treatment regimens that were the same with the exception of theophylline. A total of 183,573 patients were included. In the largest group, patients treated with ipratropium plus theophylline, compared to ipratropium alone, had a 1.11-fold increase in the risk of death (95% CI, 1.04-1.18). In comparisons of other regimens the risk of mortality associated with theophylline in the regimen was greater than regimens without theophylline (HRs from 1.17 to 1.31). In the time- varying exposure analysis, theophylline (HR=1.23 [95% CI 1.09 to 1.39]) was associated with an increased mortality risk.


Compared to similar regimens, patients in regimens that included theophylline had slightly increased risks of mortality, chronic obstructive pulmonary disease exacerbations and chronic obstructive pulmonary disease hospitalizations; however we are unable to measure the impact on other factors including symptoms and quality of life.

Journal Publications

Lee TA, Schumock GT, Bartle B, et al. Mortality risk in patients receiving drug regimens with theophylline for chronic obstructive pulmonary disease. Pharmacotherapy 2009;29:1039-53.

Pickard AS, Lee TA, Solem CT, et al. Prioritizing comparative-effectiveness research topics via stakeholder involvement: an application in COPD. Clin Pharmacol Ther 2011 Nov 2 [Epub ahead of print]. PMID: 22048220

Page last reviewed November 2017
Page originally created November 2017

Internet Citation: Research Report: Mortality Risk in Chronic Obstructive Pulmonary Disease Patients Using Theophylline. Content last reviewed November 2017. Effective Health Care Program, Agency for Healthcare Research and Quality, Rockville, MD.

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