Prognostic Factors, Genetics, and Therapy in PAH-SSD

PAH-SSD 的预后因素、遗传学和治疗

• 批准号: 7058174
• 负责人: STEPHEN C MATHAI
• 金额: $ 5.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058174
• 关键词: clinical research; disease /disorder classification; dyspneas; exercise tolerance; genetic susceptibility; human subject; human therapy evaluation; microarray technology; pathologic process; patient oriented research; postdoctoral investigator; prognosis; pulmonary hypertension; quality of life; scleroderma; simvastatin

DESCRIPTION (provided by applicant): Within the group of disorders that comprise pulmonary arterial hypertension, PAH related to scleroderma (PAH-SSD) is associated with a high mortality and current therapy for patients with this disease is limited. Despite clinical and histologic similarities to idiopathic PAH (IPAH), distinct differences exist in proposed pathogenesis, response to therapy, and survival. For instance, the origin of the classic plexiform lesion in the pulmonary vasculature may differ between these two entities. Further, although both patients with IP AH and PAH-SSD respond to epoprostenoid therapy, the magnitude of response is more profound for patients with IP AH. Ultimately, survival for patients with PAH-SSD is much poorer than for patients with IP AH. Utilizing the large number of patients in our pulmonary hypertension registry at Johns Hopkins, we propose to prospectively study patients with PAH with the following specific aims: 1) to define prognostic factors for disease progression and survival in patients with PAH-SSD compared to patients with IP AH, 2) to identify candidate genes in PAH-SSD by disease-specific cDNA microarray analyses, and 3) to evaluate the effect of simvastatin therapy on clinical outcomes as assessed by exercise capacity, Borg dyspnea score, WHO/NYHA functional class, quality of life assessed by SF-36 survey, and time to clinical worsening in patients with PAH.

描述（由申请人提供）：在包含肺动脉高压的疾病组中，与硬皮病相关的PAH（PAH-SSD）与该疾病患者的高死亡率和当前治疗有关。尽管与特发性PAH（IPAH）的临床和组织学相似性，但在拟议的发病机理，对治疗的反应和生存中仍然存在明显的差异。例如，这两个实体之间的经典丛状病变的起源可能有所不同。此外，尽管IP AH和PAH-SSD的患者均对eprolostenoid疗法有反应，但对于IP AH患者而言，反应的幅度更为深刻。最终，PAH-SSD患者的生存率比IP AH患者差得多。 Utilizing the large number of patients in our pulmonary hypertension registry at Johns Hopkins, we propose to prospectively study patients with PAH with the following specific aims: 1) to define prognostic factors for disease progression and survival in patients with PAH-SSD compared to patients with IP AH, 2) to identify candidate genes in PAH-SSD by disease-specific cDNA microarray analyses, and 3) to evaluate the effect of simvastatin通过运动能力评估的临床结果治疗，Borg呼吸困难得分，/NYHA功能类别，SF-36调查评估的生活质量以及PAH患者的临床恶化时间。