In the paper by Stolz et al. 1, bosentan deteriorated not only exercise capacity but also hypoxaemia and quality of life among subjects with severe or very severe chronic obstructive pulmonary disease (COPD). While the concept of a new drug category which could improve functional status among these patients is challenging, the theoretical background and clinical data to support the rationale for this trial 1 is rather weak.
In the study by Gunther et al. 2, the use of bosentan in 12 subjects with idiopathic pulmonary fibrosis was generally well tolerated and did not induce hypoxaemia in 12 weeks. However, there was a trend towards a decrease of forced vital capacity and diffusing capacity of the lung for carbon monoxide, while 6-min walking distance (6MWD) decreased from 320.9 m (232.96–408.84 m) to 302.9 m (205.01–400.79 m); p<0.05. Bosentan was not superior over the placebo in 6MWD in another double-blind, multicentre trial which included 158 patients with idiopathic pulmonary fibrosis 3. Since the use of bosentan among patients with parenchymal lung disease has not proved to be favourable, the hypothesis that it could be beneficial for COPD subjects because they establish elevated levels of endothelin is rather weak.
While selective pulmonary vasodilation may benefit chronic obstructive pulmonary disease patients with increased pulmonary artery pressure during stress 4, this study was not designed to prove such an effect of bosentan. The pathophysiology of exercise limitation in severe chronic obstructive pulmonary disease subjects and the ventilation/perfusion ratio mismatching, which is induced by unselective pulmonary vasodilation 5, should have been taken more seriously under consideration in the study design of Stolz et al. 1.
Statement of interest
None declared.
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