Effect of add-on therapy of tiotropium in COPD treated with theophylline

Abstract

Background

Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators.

Objective

We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients.

Methods

In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD.

Results

Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV₁) 1.5 L [62.5% predicted]). FEV₁ in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 ± 0.13 L, p < 0.001) and 8 weeks (1.60 ± 0.13 L, p < 0.001) from the baseline (1.40 ± 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p < 0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV₁.

Conclusion

Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.

Keywords:

• chronic obstructive pulmonary disease
• long acting anticholinergics agent
• tiotropium
• slow release theophylline
• combination therapy

Acknowledgements

We especially thank Dr Gail M Gauvreau of the Asthma Research Group, McMaster University, Canada, for critical reading of this manuscript. This work was supported by Nippon Boehringer Ingelheim Co, Ltd (Tokyo, Japan) and by a Grant-in-Aid for Scientific Research (B) (no. 18390244) and Grants-in-Aid for Scientific Research (B) (no. 17390244) and Exploratory Research (no. 18659244) from the Ministry of Education, Science, Sports, and Culture of Japan.

*Appendix

The Kurume COPD Study Group includes Dr Toshinobu Yokoyama and Dr Tomoko Kamimura, (Kurume University); Dr Kazuhito Taguchi, (National Hospital Organization Kyushu Medical Center); Dr Rumi Gohara and Dr Yoshikazu Tominaga (Yame General Hospital); Dr Toru Rikimaru and Dr Mamoru Nishiyama (Saiseikai Futsukaichi Hospital); Dr Koichi Azuma (Social Insurance Tagawa Hospital); Dr Kazuko Matsunaga (National Hospital Organization Omuta Hospital); and Dr Hideyuki Koga (Keisinkai Hospital).