BOSANTAN IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。特发性肺纤维化(IPF)，又称隐源性纤维性肺泡炎，是间质性肺疾病的一种独特的临床疾患。IPF是一种进行性疾病，其特征是外科肺活检的组织学类型为普通型间质性肺炎(UIP)。目前还没有任何治疗方法可以改善IPF患者的生存或生活质量。目前的治疗仍然基于先前的假设，即IPF是一个炎症过程，同时伴有肺纤维化重塑。因此，它涉及抗炎治疗，包括皮质类固醇(如泼尼松、强的松龙)、免疫抑制/细胞毒剂(如硫唑嘌呤、环磷酰胺)或两者的组合。然而，由于当前治疗方法的边际效益和严重副作用，以及对IPF发病机制的新见解，迫切需要新的治疗方法。抗纤维化治疗的目的是减少基质沉积或增加胶原分解，目前正在研究秋水仙碱、D-青霉胺、干扰素和吡非尼酮等药物。对于一些IPF患者来说，肺移植已经成为一种可行的选择。临床和实验研究表明，波生坦是安全和耐受性良好的，可以延缓IPF的进展，这种情况目前还没有确定的有效治疗方法。目前的Build-1研究调查了波生坦的适应症范围是否可能扩大到一种新的IPF患者类别。波生坦目前被批准用于治疗中到重度PAH。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is a distinct clinical disorder belonging to the spectrum of interstitial lung disease. IPF is a progressive disease characterized by the presence of a histological pattern of usual interstitial pneumonia (UIP) on surgical lung biopsy. No therapies have been shown to improve the survival or quality of life for patients with IPF. Current treatment is still based on the former presumption that IPF is an inflammatory process with concurrent remodeling of the lung by fibrosis. Consequently, it involves anti-inflammatory therapy, including corticosteroids (e.g., prednisone, prednisolone), immunosuppressive/cytotoxic agents (e.g., azathioprine, cyclophosphamide) or a combination of both. However, because of the marginal benefit and serious side effects of the current therapies, along with newer insights into the pathogenesis of IPF, novel therapeutic approaches are highly needed. Antifibrotic therapy is aimed at decreasing matrix deposition or increasing collagen breakdown and a number of agents including colchicine, D-penicillamine, interferon y, and pirfenidone, are currently under investigation. Lung transplantation has emerged as a viable option for some patients with IPF. Clinical and experimental studies suggest that bosentan would be safe and well tolerated and could delay the progression of IPF, a condition for which no established efficacious treatment is availale. The present BUILD-1 study investigates a posssible extension of the indication range of bosentan, which is currently approved for the treatment of moderate to severe PAH, to a new category of patients suffering from IPF.