Screening for schistosomiasis-associated pulmonary arterial hypertension

血吸虫病相关肺动脉高压的筛查

基本信息

批准号：
10742608
负责人：
Brian Barkley Graham
金额：
$ 22.08万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10742608
关键词：
Africa South of the Sahara Agreement Attention Biological Markers Blood Vessels Blood specimen Calibration Cardiac Catheterization Procedures Characteristics Classification Classification Scheme Clinic Clinical Clinical Data Clinical Management Collaborations Communities Country Data Data Set Development Diagnosis Diagnostic Diagnostic tests Dimensions Discrimination Disease Early Diagnosis Early treatment Echocardiography Eligibility Determination Enrollment Epidemiology Ethiopia Etiology Follow-Up Studies Future Guidelines Hand Helminths Individual Infection Letters Lung Measures Methods Nature Outcome Participant Patients Persons Phenotype Prevalence Probability Prospective cohort Prospective, cohort study Protocols documentation Provider Pulmonary Hypertension Recording of previous events Resources Risk Risk Factors Role Sampling Schistosoma Schistosoma mansoni Schistosomiasis Screening procedure Site Technology Testing Thrombospondin 1 Ultrasonography Update Validation Visit Zambia accurate diagnostics clinical predictors clinical research site cohort diagnostic criteria diagnostic tool exercise capacity follow-up high risk innovation insight low and middle-income countries noninvasive diagnosis novel novel marker novel strategies novel therapeutics participant enrollment patient screening phenomics point of care pre-clinical predictive marker predictive modeling pulmonary arterial hypertension pulmonary vascular disorder research study screening standard of care symposium therapeutic target tool trend

项目摘要

SUMMARY/ABSTRACT Due to challenges with available technology in regions of the world where schistosomiasis is endemic, the prevalence of schistosomiasis-associated pulmonary arterial hypertension (SchPAH) is unknown. SchPAH is an incurable and ultimately fatal disease for which early detection and treatment could extend the lives of those afflicted. New approaches to diagnose SchPAH are needed, as the current diagnostic criteria require invasive right heart catheterization leading to under and delayed diagnosis. An opportunity to develop noninvasive diagnostic risk scores for PAH is provided by the PVDomics dataset and a collaboration to conduct these analyses at UCSF using the PVDomics data has been established. The proposed studies will define diagnostic risk scores for PAH (i) using a broad range of clinical, echocardiographic (echo), and biomarker predictors and (ii) using predictors easily measured in low- and middle-income countries (LMIC). The risk scores would enable estimation of the probability of PAH in individuals, the PAH case-rate in clinic samples, and PAH prevalence in communities at risk. Regardless of LMIC, the scores will rely only on noninvasive predictors to support their repeated use in disease screening. After developing the risk score, its first application to will be to SchPAH disease, and will take place in the longitudinal prospective cohorts we are enrolling at 3 clinical sites in Ethiopia and Zambia, targeting 40 enrollees per site per year. We will estimate the case-rate of SchPAH by standard of care criteria and using the Aim-1 diagnostic risk score. Eligible patients will have a history of Schistosoma infection and be diagnosed with schistosomiasis-associated hepatosplenic disease (SchHSD), placing them at relatively high risk for SchPAH. At baseline and annual follow-up study visits each participant will undergo clinical and echocardiography assessments, and providing blood samples for biomarker assessments to ensure that the predictors on which the diagnostic score is based are on hand. Once it is defined, the risk score and probability of PAH will be calculated on each participants’ data, both at past and future visits, and the distribution the quantities will be summarized graphically. This study also will evaluate some biomarkers that reflect the pathobiology of SchPAH and may be particularly suitable for identifying PAH disease during its preclinical and early clinical periods, which could suggest a role as potential therapeutic targets. We believe these diagnostic tools will have enormous impact on all those worldwide who are at risk for developing PAH or living with undiagnosed PAH.

摘要/摘要由于世界上血吸虫病流行地区现有技术面临挑战，血吸虫病相关肺动脉高压 (SchPAH) 的患病率尚不清楚。无法治愈且最终致命的疾病，早期发现和治疗可以延长患者的生命由于当前的诊断标准需要侵入性，因此需要新的方法来诊断 SchPAH。右心导管检查导致诊断不足和延迟。 PVDomics 数据集提供了开发 PAH 无创诊断风险评分的机会加州大学旧金山分校使用 PVDomics 数据进行这些分析的合作已经建立。拟议的研究将使用广泛的临床、超声心动图来定义 PAH 的诊断风险评分 (i) (echo) 和生物标志物预测因子，以及 (ii) 在低收入和中等收入国家使用易于测量的预测因子 (LMIC)。风险评分将能够估计个体中 PAH 的概率、PAH 病例发生率。临床样本以及高危社区的 PAH 患病率，无论中低收入国家如何，得分仅依赖于。非侵入性预测因子支持其在疾病筛查中的重复使用。制定风险评分后，其首次应用于 SchPAH 疾病，并将在我们正在埃塞俄比亚和赞比亚的 3 个临床中心招募纵向前瞻性队列，目标为 40 名受试者我们将根据护理标准并使用 Aim-1 来估计 SchPAH 的发病率。诊断风险评分符合条件的患者将有血吸虫感染史并被诊断为血吸虫。血吸虫病相关肝脾疾病 (SchHSD)，使他们患 SchPAH 的风险相对较高。在基线和年度随访研究访问中，每个参与者都将接受临床和超声心动图检查评估，并提供血液样本进行生物标志物评估，以确保预测因子诊断评分是基于手动定义的，PAH 的风险评分和概率将是。根据每个参与者过去和未来访问的数据进行计算，以及数量的分布本研究还将评估一些反映 SchPAH 病理学的生物标志物。可能特别适合在临床前和临床早期阶段识别 PAH 疾病，可以表明作为潜在治疗靶点的作用。我们相信这些诊断工具将对全世界所有面临疾病风险的人产生巨大影响患有 PAH 或患有未确诊的 PAH。