The Role and Consequences of Anemia in Children with Pneumonia

描述（由申请人提供）：肺炎是全球幼儿死亡的主要原因，主要发生在低收入和中等收入国家（LMIC）。由于肺炎患儿最终死于呼吸衰竭，贫血等影响组织供氧的因素可能会影响患者的预后。贫血在中低收入国家非常常见，影响到撒哈拉以南非洲和东南亚三分之二的儿童，它可能是一些肺炎患者的治疗目标。本研究的总体目标是描述重症肺炎和中/重度贫血合并住院儿童的结局，以便获得初步数据，为未来的前瞻性治疗试验提供信息。在我们之前的工作中，我们发现贫血和高海拔的结合对患有严重肺炎的儿童尤其有害。这项研究没有包括许多患有严重贫血的儿童；由此推而广之，我假设严重贫血与肺炎的不良预后有关，即使在低海拔地区也是如此。我将通过对我们在乌干达西南部的合作机构姆巴拉拉地区转诊医院收治的患有严重肺炎和中度/重度贫血的儿童进行观察性研究来检验这一假设。在Aim 1中，我将测量血红蛋白对重症肺炎恢复的影响。在Aim 2中，我将评估低血红蛋白对组织缺氧的影响，通过血乳酸来测量。纠正严重贫血在某些情况下需要输血红细胞（RBC）， Aim 3将通过测量输血患者输血相关循环超负荷（TACO）的风险来评估严重肺炎患者输血的安全性。更大的研究目标是确定影响肺炎儿童预后的可改变的风险因素。我已经接受过肺病和重症监护方面的临床培训。作为F32培训计划的一部分，我将在Patricia Hibberd博士的指导下培养临床和转化研究的技能。Patricia Hibberd博士是呼吸道感染、全球儿童健康和以患者为导向的临床研究方面的知名专家，她在美国和低收入国家进行了关于儿童肺炎预防和治疗的第四期研究。培训将通过全球卫生、研究方法、传染病流行病学、营养和高级生物静力学等课程得到加强。我预计，这项研究的结果将为全球公共卫生工作提供信息，以减少儿童肺炎死亡率。

DESCRIPTION (provided by applicant): Pneumonia is the leading cause of death among young children worldwide, primarily in low and middle-income countries (LMIC). Since children with pneumonia ultimately die of respiratory failure, factors such as anemia that affect delivery of oxygen to the tissues may affect patient outcomes. Anemia is very common in LMIC, affecting two-thirds of children in Sub-Saharan Africa and Southeast Asia, and it may be a target for therapy in some patients with pneumonia. The overarching goal of this research is to describe the outcomes of children hospitalized with the combination of severe pneumonia and moderate/severe anemia in order to obtain preliminary data that will inform a future prospective treatment trial. In our prior work, we found that the combination of anemia and high altitude is particularly harmful among children with severe pneumonia. This study did not include many children with severe anemia; by extension, I hypothesize that severe anemia will be associated with poor outcomes in pneumonia, even at low altitude. I will test this hypothesis through an observational study of children admitted with severe pneumonia and moderate/severe anemia to Mbarara Regional Referral Hospital, our collaborating institution in Southwest Uganda. In Aim 1, I will measure the effect of hemoglobin on time to recovery from severe pneumonia. In Aim 2, I will evaluate the effect of low hemoglobin on tissue hypoxia, as measured by blood lactate. Correcting severe anemia will in some cases require red blood cell (RBC) transfusion, and Aim 3 will evaluate the safety of RBC transfusions among patients with severe pneumonia by measuring the risk of transfusion-associated circulatory overload (TACO) in patients receiving transfusions. The larger research goal is to identify modifiable risk factors that influence outcomes in children with pneumonia. I have already received clinical training in pulmonary disease and critical care. As part of the F32 training program, I will develop skills in clinical ad translational research through mentorship by Dr. Patricia Hibberd, an established expert in respiratory infections, global child health, and patient-oriented clinical research who has conducted translational through Phase IV studies on the prevention and treatment of childhood pneumonia in the US and in low-income countries. The training will be augmented by coursework in global health, research methods, infectious disease epidemiology, nutrition, and advanced biostatics. I anticipate that the findings from this research will inform global public health efforts to reduce pneumonia mortality among children.