Case-Control Study of Methamphetamine in Pulmonary Arterial Hypertension

甲基苯丙胺治疗肺动脉高压的病例对照研究

• 批准号: 10312558
• 负责人: Steven M Kawut
• 金额: $ 85.12万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-20 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10312558
• 关键词: Address; Adult; Affect; Agonist; Alleles; Biological; Carboxylesterase 1; Case-Control Studies; Cell Death; Cells; Cessation of life; Chronic; Clinical; Clinical Trials; Complication; Data; Dexfenfluramine; Disease; Emergency department visit; Endothelial Cells; Endothelium; Epidemic; Epidemiology; Esters; Exercise; Fenfluramine; Genetic; Goals; Grant; Heart failure; Heritability; Hospitalization; Human; Injury; Knowledge; Lead; Link; Lung; Lung Transplantation; Metabolic; Metabolism; Methamphetamine; Midwestern United States; Minor; Modification; Multicenter Studies; North America; Outcome; Oxidative Stress; Patient observation; Patients; Pharmaceutical Preparations; Prevalence; Prospective cohort study; Proteomics; Pulmonary Hypertension; Recording of previous events; Registries; Reporting; Right Ventricular Dysfunction; Risk; Risk Estimate; Risk Factors; Route; Side; Single Nucleotide Polymorphism; Smooth Muscle Myocytes; Socioeconomic Status; Toxin; United States; Vascular Diseases; base; case control; cell injury; clinical predictors; comorbidity; epidemiology study; genetic variant; high risk; improved; improved outcome; infancy; insight; methamphetamine use; methamphetamine user; mitochondrial dysfunction; novel; novel therapeutic intervention; patient oriented research; personalized medicine; preclinical study; premature; primary pulmonary hypertension; pulmonary arterial hypertension; receptor; research study; risk stratification; screening guidelines; side effect; stimulant abuse; treatment strategy; vascular bed; virtual

The long-term objectives of this application are to establish the epidemiological association between methamphetamine use and pulmonary arterial hypertension. Methamphetamine and other stimulant abuse have been increasing across the United States and the world with several known complications. Pulmonary arterial hypertension has been suspected to occur as a sequela, however this has never been studied in a rigorous multicenter epidemiologic study. Preliminary findings have suggested that carboxylesterase 1 (CES1) may be an important genetic modifier in the setting of methamphetamine use leading to pulmonary arterial hypertension. The Specific Aims are 1) to determine whether methamphetamine use is associated with PAH in a case-control study and whether this association is modified by genetic variants in (or activity of) CES1; 2) to determine the risk factors for clinical worsening in patients with methamphetamine-associated pulmonary arterial hypertension in comparison with idiopathic pulmonary arterial hypertension in a prospective cohort study; and 3) to understand if reductions in CES1 activity result in human pulmonary endothelial cell damage in methamphetamine-associated pulmonary arterial hypertension. Patient-oriented research studies will be conducted in a multicenter study group to address these epidemiologic questions.

这项应用的长期目标是建立两者之间的流行病学联系 甲基苯丙胺使用和肺动脉高压。甲基苯丙胺和其他兴奋剂滥用 在美国和世界各地都在增加，并出现了几个已知的并发症。肺 动脉高血压被怀疑是一种后遗症，然而，这方面的研究从未在 严格的多中心流行病学研究。初步研究表明，羧酸酯酶1(CES1) 可能是甲基苯丙胺使用导致肺动脉形成的重要遗传修饰物 高血压。具体目的是1)确定甲基苯丙胺的使用是否与 一项病例对照研究以及这种关联是否被CES1的遗传变异(或活性)所改变；2) 确定甲基苯丙胺相关性肺病患者临床恶化的危险因素 前瞻性队列研究中动脉高血压与特发性肺动脉高压的比较 研究；以及3)了解CES1活性降低是否会导致人肺内皮细胞损伤 甲基苯丙胺相关性肺动脉高压。以患者为中心的研究将是 在一个多中心研究小组中进行，以解决这些流行病学问题。