PURPOSE: Specific therapy of pulmonary hypertension due to lung disease (LD) is currently not recommended because the effects on gas exchange through the inhibition of hypoxic pulmonary vasoconstriction.
METHODS: We assessed safety, clinical impact and blood gases effects of non-selective endothelin receptor antagonist (ETRA) bosentan (B) in patients with severe PH associated with LD. 15 patients with LD and “out-of-proportion” PH, defined as severe pre-capillary PH (mean pulmonary arterial pressure >45 mmHg and pulmonary wedge pressure <15 mmHg) including 8 with chronic idiopathic interstitial pneumonia (IIP) and 7 with COPD were considered. Blood gases were analyzed at -12 , 0, 12 and 24 weeks (wks) from the treatment measuring paO2 and paCO2 ; alveolar to arterial O2 gradient ( A-aO2 ) was calculated from alveolar gas equation. WHO functional class, liver enzymes, 6-min walk test (6MWT) were also assessed No significant difference was observed in haemodynamics between IIP and COPD patients No major side effects were observed during the follow-up. All patients well tolerated B at common doses.
RESULTS: At 24 weeks WHO functional class (3.1±0.9 vs 2.9±0.8; p=ns) and distance at 6MWT (284±54 vs 273±62 m; p=ns) did not change from baseline. In IIP patients B was associated to increased A-aO2 (46±8 vs T0 32±4 mmHg and T-12wks 303 mm Hg p<0.05) Differently,there was no significant difference in A-aO2 in COPD patients (30±5 vs 27±7 mmHg; p=ns).
CONCLUSION: In patients with severe PH associated to LD 24 weeks of B therapy was safe and well tolerated but it was not associated to significant change in clinical outcome.
CLINICAL IMPLICATIONS: Long term treatment with B was associated to significant abnormalities in gas exchange in IIP patients while did not affect gas exchange in severe PH associated to COPD.
DISCLOSURE: Michele D’Alto, No Financial Disclosure Information; No Product/Research Disclosure Information