To the Editor:

Mathioudakis A et al. discussed an increased risk of mortality in Respimat compared to HandiHaler. Our recent article by Asakura Y et al. showed only the short-term usefulness and safety of Respimat in a small population study.⁽¹⁾ Certainly, long-term safety, especially the difference in mortality between devices, is an important problem to be solved. Singh S et al. first showed the possibility of an increased risk of mortality in Respimat compared to HandiHaler by meta-analysis.⁽²⁾ However, this meta-analysis is constructed from limited data from published articles. It is not the final opinion that Respimat increases mortality compared to HandiHaler in the patients with COPD. The difference of mortality between tiotropium devices should be explained by a large multicenter study, which is ongoing now.⁽³⁾ Of course, discussion about the differences in mortality between HandiHaler and Respimat is welcome. However, I think the opinion about an increased mortality in Respimat should be more carefully and not definitively discussed.

The authors of the letter suggested that an increased rate of sudden cardiac deaths could be predicted by high peak plasma concentrations of tiotropium delivered by Respimat. However, as far as I know, there is no direct evidence explaining the relationship between an increased plasma concentration of tiotropium and an increased risk of mortality. Moreover, 5 μg of tiotropium delivered by Respimat showed almost the same plasma concentration of 18 μg of tiotropium delivered by HandiHaler in the study of van Noord JA et al.⁽⁴⁾ The relationship between an increased risk of mortality and a peak plasma concentration of tiotropium should be discussed with great caution.