Screening for schistosomiasis-associated pulmonary arterial hypertension

总结/摘要 由于世界上血吸虫病流行地区现有技术的挑战， 肺动脉高压（SchPAH）的患病率尚不清楚。SchPAH是一种 无法治愈，最终致命的疾病，早期发现和治疗可以延长这些人的生命， 受折磨需要新的方法来诊断SchPAH，因为目前的诊断标准需要侵入性检查。 右心导管插入术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 并建立了一个合作，在UCSF使用PVDomics数据进行这些分析。的 拟议的研究将使用广泛的临床、超声心动图、 （ii）使用低收入和中等收入国家容易测量的预测指标 （LMIC）。风险评分将能够估计个体中PAH的概率， 临床样本和高危社区的PAH患病率。不考虑LMIC，分数将仅依赖于 非侵入性预测，以支持其在疾病筛查中的重复使用。 在开发风险评分后，其首次应用将是SchPAH疾病，并将在 我们在埃塞俄比亚和赞比亚的3个临床研究中心招募了纵向前瞻性队列，目标是40名入组者 每年每个站点。我们将通过标准治疗标准和使用Aim-1估计SchPAH的病例率 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 染色体相关性肝脾疾病（SchHSD），使他们处于SchPAH的相对高风险中。 在基线和年度随访研究访视时，每名受试者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 诊断分数是基于手头的。一旦定义，PAH的风险评分和概率将是 根据每名参与者过去和未来访视的数据计算，以及数量的分布 以图形方式总结。本研究还将评估一些反映SchPAH病理生物学的生物标志物 并且可能特别适合于在PAH疾病的临床前和早期临床期间鉴定PAH疾病， 可以作为潜在的治疗靶点。 我们相信，这些诊断工具将对全世界所有有风险的人产生巨大影响。 患有PAH或患有未确诊的PAH。

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.