Urinary Proadrenomedullin to Improve Risk Stratification of Children with Community-Acquired Pneumonia

尿肾上腺髓质素原可改善社区获得性肺炎儿童的风险分层

• 批准号: 9809185
• 负责人: Todd Adam Florin
• 金额: $ 9.66万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-03 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9809185
• 关键词: 18 year old; Accident and Emergency department; Adult; Anti-inflammatory; Anxiety; Bacterial Infections; Biological Assay; Biological Markers; Blood; C-reactive protein; Child; Childhood; Clinical; Clinical Data; Collection; Communities; Data; Deterioration; Development; Diagnosis; Diagnostic tests; Disadvantaged; Disease; Disease Marker; Disease Progression; Evaluation; Exposure to; Goals; Hospitalization; Infection; Inflammation; Intervention; Lead; Literature; Lower Respiratory Tract Infection; Measurable; Measurement; Measures; Medical Errors; Methods; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Nosocomial Infections; Outcome; Pain; Patients; Peptides; Pilot Projects; Plasma; Pleural effusion disorder; Pneumonia; Prognostic Marker; Property; Prospective cohort study; Research; Research Personnel; Resources; Respiratory Tract Infections; Risk; Risk stratification; Role; Severities; Severity of illness; Specimen; Stress; System; Testing; Time; United States; Urinary tract infection; Urine; Venipunctures; White Blood Cell Count procedure; Work; adrenomedullin; antimicrobial; base; clinical care; clinical risk; cost; cost effectiveness; evidence base; high risk; high risk population; improved; improved outcome; innovation; mortality; neutrophil; predict clinical outcome; prevent; procalcitonin; prognostic; tool; urinary

PROJECT SUMMARY/ABSTRACT Although community-acquired pneumonia (CAP) is one of the most common serious bacterial infections in children, no validated decision tools exist to gauge illness severity among children with CAP. Without objective tools, management decisions are inefficient and potentially inaccurate, resulting in the use of unnecessary tests, therapies and hospitalizations in low-risk children or delays in critically important therapies in those at high risk of severe outcomes. The long-term goal of this research is to improve risk stratification of children with lower respiratory tract infections. Proadrenomedullin (proADM) is a vasodilatory peptide that, when measured in blood, has shown great potential to improve severity prediction in adults and children with CAP. Obtaining blood for biomarker measurements in children has several disadvantages, including pain, anxiety, invasiveness, and need for technical and procedural expertise. Proadrenomedullin can also be measured in urine, offering several important advantages, including ease of collection, cost effectiveness, and lack of discomfort. There is a paucity of data, however, on the role of urinary proADM in predicting clinical outcomes in children with suspected CAP. The overall objective of this R03 is to perform a proof-of-principle study to examine the ability of urinary proADM to predict clinical outcomes and disease severity in pediatric CAP. The scientific premise of the proposed study is based on (a) strong preliminary data from the PI's K23 that plasma proADM is associated with severe outcomes in suspected CAP in children, (b) feasibility testing finding a normally distributed range of concentrations of proADM in urine, (c) data demonstrating that plasma and urinary proADM levels are correlated, and (d) a body of literature suggesting that proADM is strongly associated with severe outcomes in adults with CAP. The specific aim of this R03 is to evaluate the association between urinary proADM levels and clinical outcomes in children with suspected CAP. The central hypothesis is that higher levels of urinary proADM will be associated with severe clinical outcomes. The investigators will leverage existing clinical data and urine specimens collected from 407 children at the time of initial evaluation as part of the PI's K23, a prospective cohort study of children 3 months to 18 years of age with suspected CAP who presented to the emergency department (ED). The proposed research is innovative in that it represents a new and substantive departure from the status quo by shifting the paradigm from inaccurate, subjective, or invasive risk stratification methods to an objective, accurate, rapid, and non-invasive approach that can be applied across multiple settings. This contribution is significant because effectively predicting disease severity in children with suspected CAP using proADM will ultimately improve the accuracy and reliability of management decisions by stratifying children into a high-risk group in need of focused and intensive therapies and a low-risk group for whom such therapies and resource use is unnecessary, ineffective, and potentially harmful.

项目总结/摘要 虽然社区获得性肺炎（CAP）是最常见的严重细菌感染之一， 儿童，没有经过验证的决策工具存在，以衡量疾病的严重程度与CAP儿童。没有客观 工具，管理决策效率低下，可能不准确，导致使用不必要的 低风险儿童的检查、治疗和住院治疗，或 严重后果的高风险。本研究的长期目标是改善儿童的危险分层 患有下呼吸道感染。肾上腺髓质素原（proADM）是一种血管舒张肽，当 在血液中测量，已显示出极大的潜力，以提高预测严重程度的成人和儿童与CAP。 在儿童中获得用于生物标志物测量的血液有几个缺点，包括疼痛，焦虑， 侵入性，以及需要技术和程序专业知识。肾上腺髓质素前体也可以在 尿液，提供了几个重要的优势，包括易于收集，成本效益，和缺乏 不适然而，关于尿proADM在预测糖尿病患者临床结局中的作用的数据很少。 疑似CAP的儿童本R 03的总体目标是进行原理验证研究， 研究尿proADM预测儿科CAP临床结局和疾病严重程度的能力。的 拟议研究的科学前提是基于（a）来自PI K23的强有力的初步数据， proADM与儿童疑似CAP的严重结果相关，（B）可行性测试发现， 尿中proADM浓度的正态分布范围，（c）表明血浆和 尿proADM水平是相关的，和（d）大量文献表明proADM是强烈的 与成人CAP患者的严重结局相关。本R 03的具体目的是评估 疑似CAP患儿尿proADM水平与临床结局的相关性中央 假设较高水平的尿proADM将与严重的临床结果相关。的 研究人员将利用现有的临床数据和从407名儿童中收集的尿液样本， 作为PI K23的一部分进行的初步评价，这是一项针对3个月至18岁儿童的前瞻性队列研究， 到急诊科（艾德）就诊的疑似CAP患者。该研究具有创新性， 它代表了一个新的和实质性的脱离现状， 将不准确、主观或侵入性的风险分层方法转变为客观、准确、快速和非侵入性的方法。 这种方法可以应用于多种环境。这一贡献是重要的，因为有效地 使用proADM预测疑似CAP儿童的疾病严重程度将最终提高准确性 和可靠性的管理决策，将儿童分为高风险群体，需要重点和 强化治疗和低风险组，对他们来说，这种治疗和资源使用是不必要的，无效的， 并且可能有害。