Screening for schistosomiasis-associated pulmonary arterial hypertension

摘要/摘要 由于世界上血吸虫病流行地区现有技术的挑战， 血吸虫病相关性肺动脉高压(SchPAH)的患病率尚不清楚。SchPAH是一种 无法治愈并最终致命的疾病，早期发现和治疗可以延长这些人的生命 痛苦不堪。由于目前的诊断标准需要侵入性的，因此需要新的方法来诊断SchPAH 右心导尿术导致漏诊和延误诊断。 PVDomics数据集提供了开发PAH非侵入性诊断风险评分的机会 已经建立了使用PVDomics数据在加州大学旧金山分校进行这些分析的合作。这个 拟议的研究将使用广泛的临床、超声心动图来确定PAH(I)的诊断风险评分 (2)使用易于在低收入和中等收入国家衡量的预测指标 (LMIC)。风险分数将使个人能够估计发生PAH的概率， 临床样本和高危社区的多环芳烃流行率。无论LMIC如何，分数将仅取决于 支持在疾病筛查中重复使用的非侵入性预测指标。 在开发了风险评分后，它将第一次应用于SchPAH病，并将在 我们在埃塞俄比亚和赞比亚的3个临床地点招募了纵向前瞻性队列，目标是40名参与者 每个站点每年。我们将通过护理标准和使用AIM-1来评估SchPAH的发病率 诊断风险分数。符合条件的患者将有血吸虫感染史，并被诊断为 血吸虫病相关性肝脾疾病(SchHSD)，使他们处于相对较高的SchPAH风险。 在基线和年度随访研究中，每个参与者都将接受临床和超声心动图检查。 评估，并为生物标记物评估提供血液样本，以确保 诊断分数是基于手头上的。一旦它被定义，PAH的风险分数和概率将是 根据每个参与者过去和未来访问的数据以及数量的分布情况进行计算 以图形方式汇总。本研究还将评估一些反映SchPAH病理生物学的生物标志物 可能特别适合于在临床前和临床早期识别PAH疾病，这 可能会成为潜在的治疗靶点。 我们相信，这些诊断工具将对全球所有面临癌症风险的人产生巨大影响 发展成PAH或与未确诊的PAH生活在一起。

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.