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）：在包括肺动脉高压的疾病组中，与硬皮病相关的 PAH (PAH-SSD) 与高死亡率相关，并且目前对该疾病患者的治疗是有限的。尽管与特发性 PAH (IPAH) 的临床和组织学相似，但在发病机制、治疗反应和生存方面存在明显差异。例如，这两个实体之间肺血管系统中经典丛状病变的起源可能不同。此外，尽管 IP AH 和 PAH-SSD 患者均对依前列素治疗有反应，但 IP AH 患者的反应程度更为深刻。最终，PAH-SSD 患者的生存率比 IP AH 患者要差得多。利用约翰·霍普金斯大学肺动脉高压登记处的大量患者，我们建议对 PAH 患者进行前瞻性研究，其具体目的如下：1) 与 IP AH 患者相比，确定 PAH-SSD 患者疾病进展和生存的预后因素，2) 通过疾病特异性 cDNA 微阵列分析来识别 PAH-SSD 中的候选基因，3) 评估辛伐他汀的效果 治疗对临床结果的评估包括运动能力、Borg 呼吸困难评分、WHO/NYHA 功能分级、SF-36 调查评估的生活质量以及 PAH 患者临床恶化的时间。