Effect of bosentan upon pulmonary hypertension in chronic obstructive pulmonary disease

Abstract

Pulmonary hypertension (PH) in chronic obstructive pulmonary disease [COPD] is mainly determined by hypoxemia under respiratory failure by means of the functional hypoxemic vasoconstrictor response. Organic changes of vessels, pulmonary vascular remodelling, is gaining increasing relevance. An imbalance of endothelial products takes place with overload of vasoconstrictors and thrombogenic autacoids over vasodilators and anticoagulant factors. Among vasoconstrictors, endothelin is claimed to be an important factor. Our aim is to assess the effect of the anti-endothelin drug Bosentan on pulmonary hemodynamics and lung function in patients affected by COPD and PH. Bosentan was administered to 16 patients for a period of 18 months, while another 16 patients with overlapping features was used as a control group. Pulmonary function test, hemodynamics, effort performance, dyspnoea ratings and quality of life were recorded at the beginning and after 18 months under stable state. Bosentan treatment resulted in a significant improvement of PH from 37 + 5 to 31 + 6mm Hg and pulmonary vascular resistance from 442 + 192 to 392 + 180dynes cm(2) and 6MWD from 256 + 118 to 321 + 122m and BODE index from 6.6 + 2.8 to 5.5 + 3U. The effect was most striking in the 30% of patients in GOLD stage III and IV. Most patients in stage IV did not improve, but in all patients the treatment stopped the progressive worsening of hemodynamics over time. The study also highlights the need to identify patients with high pulmonary arterial pressure contrasting with moderate respiratory disease stages, in whom the predominant problem is evidently vascular disease. This preliminary report suggests that the use of Bosentan in the treatment of PH in COPD is beneficial.