In COPD, Are Sepsis Outcomes Better When a Bronchodilator Doubles as an Anti-inflammatory?

Nicholas Gross, MD, PhD


October 26, 2017

Association of Pre-hospital Theophylline Use and Mortality in Chronic Obstructive Pulmonary Disease Patients With Sepsis

Shih YN, Chen YT, Chu H, et al
Respir Med. 2017;125:33-38


Sepsis is a life-threatening disorder, and data show that its incidence doubled from 2000 through 2008.[1] Sepsis is the most expensive disease condition in the United States, with annual hospital costs of approximately $24 billion and climbing.[2] In chronic obstructive pulmonary disease (COPD),sepsis is not uncommon and mortality is high. To address this problem, investigators in Taiwan performed a study to determine whether early use of the bronchodilator theophylline in patients with COPD and sepsis reduced mortality and other related outcomes.

Study Summary

This propensity score–matched study included over 100,000 patients with COPD, equally divided between theophylline users and nonusers. Theophylline users had used the drug or had received a prescription for the drug at least 30 days before admission to the hospital. The primary outcome was 30-day mortality after hospitalization with a sepsis diagnosis.

The two groups were well balanced with respect to medication use, comorbidities, and other demographics of importance. One potential feature of interest was that systemic steroids had been used by more than 20% of patients, whereas inhaled corticosteroids had been used by only 0.6%. This feature was similar in both study groups, but it differs extremely from general practice in the United States. Also, in Taiwan, very many COPD patients were receiving maintenance theophylline, which is not typical in US practice either.

Compared with non-theophylline users, theophylline users experienced significantly lower mortality at 30 days, 180 days, and 1 year. Their overall mortality was about 4% lower. They also experienced lower mortality risk in-hospital and lower use of mechanical ventilation. The authors suggested that the difference may be due in part to an anti-inflammatory effect of theophylline.


The study is interesting but has a major problem in that it is retrospective. Can one be certain that theophylline users were not different from nonusers in a way that protected them from mortality? The fact that features of the patients' demographic and clinical characteristics were quite similar supports the idea that theophylline users were not systematically different and that theophylline use and no other cause explains the better outcome of theophylline users.

The trial was conducted entirely in Taiwan, which raises the question of whether the theophylline effect applies to other ethnicities. Other studies will be required to support the present findings.

The potential action of theophylline is intriguing. Theophylline is sometimes characterized as an anti-inflammatory agent, and its anti-inflammatory action has been shown to be mediated via multiple adenosine receptors.[3] Its use in modest amounts would seem to be worthy of consideration for patients with COPD.


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