Screening for schistosomiasis-associated pulmonary arterial hypertension

血吸虫病相关肺动脉高压的筛查

• 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
• 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

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 由于在世界各地的可用技术挑战，在世界各地，血吸虫病是内在的， 血吸虫病相关的肺动脉高压（SchpaH）的患病率尚不清楚。 Schpah是一个 早期检测和治疗可能延长那些人的生命 折磨。需要新的诊断Schpah的方法，因为当前的诊断标准需要侵入性 右心导管插入术导致诊断和延迟诊断。 PvDomics DataSet提供了开发PAH的无创诊断风险评分的机会 并且已经建立了使用PVDONACS数据在UCSF进行这些分析的合作。这 拟议的研究将使用广泛的临床，超声心动图定义PAH（i）的诊断风险评分 （回声），以及生物标志物预测因子和（ii）在低收入和中等收入国家中易于测量的预测变量 （LMIC）。风险评分将使PAH中PAH的可能性，PAH案例率估算 诊所样本和有风险社区的PAH患病率。不管LMIC如何，分数只会依靠 无创的预测因子，以支持其在疾病筛查中的反复使用。 在制定风险评分之后，其第一个应用将是施帕疾病，并将在 纵向前瞻性队列我们正在埃塞俄比亚和赞比亚的3个临床部位入学，目标40个 每年的每个站点。我们将按照护理标准估算施帕的案件率，并使用AIM-1 诊断风险评分。符合条件的患者将有血吸虫感染的病史，并被诊断出患有 与血吸虫病相关的肝疾病（SCHHSD），使其对Schpah的风险相对较高。 在基线和年度随访研究访问时，每个参与将进行临床和超声心动图 评估，并为生物标志物评估提供血液样本，以确保预测因素 诊断分数基于手。定义后，PAH的风险评分和概率将为 根据过去和将来的访问，根据每个参与者的数据计算，数量将是 以图形方式汇总。这项研究还将评估一些反映Schpah病理生物学的生物标志物 并且可能特别适合在临床前和早期临床期间鉴定PAH疾病 可以暗示作为潜在治疗靶标的作用。 我们认为，这些诊断工具将对有面临风险的所有风险的所有诊断工具产生巨大影响 开发PAH或用未诊断的PAH生活。