Ahmadi-Simab K, Hellmich B, Gross W L
Department of Rheumatology, University Hospital of Schleswig-Holstein, Campus Lübeck and Rheumaklinik Bad Bramstedt, Germany.
Eur J Clin Invest. 2006 Sep;36 Suppl 3:44-8. doi: 10.1111/j.1365-2362.2006.01695.x.
The oral dual endothelin (ET) antagonist bosentan has been established as a cornerstone in the treatment of pulmonary arterial hypertension (PAH). ET is believed to be a key pathogenic mediator in systemic sclerosis (scleroderma, SSc), causing fibrotic, hypertrophic and inflammatory processes. PAH is one of the resulting deleterious effects in approximately 15% of SSc patients.
This was an open-label prospective observational study of 8 patients aged 34-73 years with symptomatic, severe PAH related to SSc (WHO class III or IV) and mostly, lung fibrosis. PAH diagnosis was ascertained with echocardiography or right heart catheterization. Patients were treated on top of diuretics and anticoagulants with bosentan 62.5 mg twice daily for 4 weeks followed by a maintenance dose of 125 mg twice daily.
The mean 6-minute walk distance (data available in 7 patients) increased from 71.9 (+/- 54.7) m at baseline to 191.9 (+/- 104.6) m after 3 months (P = 0.012) and to 202.6 (+/- 108.1) m after 6 months (P = 0.011), respectively. Six of 8 patients improved in the 6-minute walk test, and these 6 patients also improved in World Health Organization functional class. Two patients did not sufficiently respond to bosentan therapy; one of them died. The tolerability of bosentan was good, and there were no discontinuations. Elevations of hepatic aminotransferases above 3 times the upper limit of normal were not recorded.
Bosentan treatment was well tolerated in this cohort of SSc patients with interstitial lung disease and was effective for treatment of severe PAH in the majority of patients.
口服双重内皮素（ET）拮抗剂波生坦已成为治疗肺动脉高压（PAH）的基石。ET被认为是系统性硬化症（硬皮病，SSc）的关键致病介质，可引发纤维化、肥厚和炎症过程。PAH是约15%的SSc患者产生的有害后果之一。
这是一项开放标签的前瞻性观察研究，纳入了8例年龄在34 - 73岁之间、患有与SSc相关的症状性重度PAH（WHO III或IV级）且大多伴有肺纤维化的患者。通过超声心动图或右心导管检查确定PAH诊断。患者在使用利尿剂和抗凝剂的基础上，接受波生坦治疗，初始剂量为62.5 mg，每日两次，持续4周，随后维持剂量为125 mg，每日两次。
7例患者有6分钟步行距离数据，其平均6分钟步行距离从基线时的71.9（±54.7）米分别增加到3个月后的191.9（±104.6）米（P = 0.012）和6个月后的202.6（±108.1）米（P = 0.011）。8例患者中有6例在6分钟步行试验中有所改善，这6例患者在世界卫生组织功能分级中也有所改善。2例患者对波生坦治疗反应不佳；其中1例死亡。波生坦的耐受性良好，无停药情况。未记录到肝转氨酶升高超过正常上限3倍的情况。
在这组患有间质性肺病的SSc患者中，波生坦治疗耐受性良好，对大多数患者的重度PAH治疗有效。
