The Role and Consequences of Anemia in Children with Pneumonia

描述(申请人提供)：肺炎是全球幼儿死亡的主要原因，主要是在低收入和中等收入国家(LMIC)。由于肺炎儿童最终死于呼吸衰竭，贫血等影响组织氧气输送的因素可能会影响患者的预后。贫血在LMIC中非常常见，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。这项研究的首要目标是描述患有严重肺炎和中度/重度贫血的住院儿童的结果，以便获得初步数据，为未来的前瞻性治疗试验提供参考。在我们之前的工作中，我们发现贫血和高原的结合对重症肺炎的儿童尤其有害。这项研究并不包括很多患有严重贫血的儿童；推而广之，我假设严重贫血与肺炎的不良结局有关，即使在低海拔地区也是如此。我将通过一项对姆巴拉拉地区转诊医院入院的患有严重肺炎和中/重度贫血的儿童的观察性研究来验证这一假设。姆巴拉拉地区转诊医院是我们在乌干达西南的合作机构。在目标1中，我将测量血红蛋白对严重肺炎康复时间的影响。在目标2中，我将评估低血红蛋白对血乳酸测量的组织缺氧的影响。在某些情况下，纠正严重贫血将需要输注红细胞(RBC)，目标3将通过测量接受输血的患者发生输血相关循环过载(TACO)的风险，来评估在重症肺炎患者中输注RBC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危险因素。我已经接受过肺部疾病和重症护理的临床培训。作为F32培训计划的一部分，我将通过Patricia Hibberd博士的指导来培养临床和翻译研究的技能，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，曾在美国和低收入国家开展过儿童肺炎预防和治疗的翻译至第四阶段研究。培训将通过全球卫生、研究方法、传染病流行病学、营养学和高级生物静力学方面的课程来加强。我预计，这项研究的结果将为全球公共卫生努力降低儿童肺炎死亡率提供信息。

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.