Invasive aspergillosis complicating severe influenza

侵袭性曲霉病并发严重流感

• 批准号: 10180901
• 负责人: M. Hong Thi NGUYEN
• 金额: $ 19.48万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-04 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10180901
• 关键词: Address; Admission activity; Antifungal Agents; Aspergillosis; Aspergillus; Aspergillus fumigatus; Attention; Awareness; Biological Assay; Bronchoalveolar Lavage Fluid; Case Study; Centers for Disease Control and Prevention (U.S.); Characteristics; Clinical; Clinical Research; Clinical Trials; Communicable Diseases; Complication; Consensus; Consumption; Country; Critical Care; Data; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Marker; Disease Outcome; Early Diagnosis; Enrollment; Epidemiology; Europe; European; Fostering; Future; Hospitals; Host Defense; Immunocompromised Host; Incidence; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A virus; Intensive Care Units; International; Knowledge; Laboratory Study; Liquid substance; Literature; Lung diseases; Medical center; Medicine; Molds; Morbidity - disease rate; Multicenter Studies; Mycoses; Pathogenesis; Patient Care; Patients; Performance; Physicians; Population; Prevention strategy; Prospective Studies; Reporting; Research Personnel; Respondent; Risk; Risk Factors; Seasons; Sensitivity and Specificity; Serum; Side; Societies; Standardization; State Hospitals; Surveys; Testing; The science of Mycology; Time; Translational Research; Uncertainty; United States; accurate diagnostics; base; cost; design; disease diagnosis; epidemiology study; follow-up; galactomannan; immunosuppressed; improved; indexing; influenza infection; lateral flow assay; member; mortality; multidisciplinary; novel; pandemic disease; performance tests; point of care; point of care testing; prospective; regional difference; stem; superinfection; treatment strategy

Project Summary Invasive infections by Aspergillus fumigatus and other Aspergillus species are leading causes of mortality and morbidity among profoundly immunosuppressed hosts. Recently, invasive aspergillosis has been described as a complication of severe influenza infection, predominantly among patients who lack traditional aspergillosis risk factors. Despite an increasing number of case reports of influenza-associated aspergillosis (IAA), the incidence and clinical features of the disease in the United States (US) are unknown. Whereas risk factors for aspergillosis are well described in immunosuppressed populations, they have not been defined for patients with severe influenza. In the largest studies of IAA to date, investigators retrospectively diagnosed the disease in 14%-19% of intensive care unit (ICU) patients with influenza at 7 European hospitals from 2009-16; the mortality rate of IAA was 50%. Comparable incidence has been described in retrospective reports from single ICUs, but rates of Aspergillus superinfections in most multi-center studies of severe influenza have been lower. In the absence of systematic testing for aspergillosis among patients with severe influenza, it is possible that IAA is under- recognized by US clinicians and under-reported in the literature. At the same time, incidence may be overstated in the retrospective European studies by liberal acceptance of serum or bronchoalveolar lavage fluid (BALf) galactomannan as definitive markers of disease. Our objectives in this project are to define the incidence, clinical characteristics, and risk factors of IAA by conducting the first prospective study of the disease in the US. We will employ strict IAA case definitions and systematic serum and BALf galactomannan diagnostic testing of ICU patients with severe influenza. We hypothesize that we will demonstrate rates of IAA in the US that are comparable to those reported in Europe, and that a novel point-of-care galactomannan lateral flow assay (LFA) will demonstrate strong sensitivity and specificity for diagnosing IAA. In aim 1, we will conduct a prospective, observational clinical study of IAA in ICUs at 4 large medical centers from different regions of the US. In aim 2, we will evaluate the performance of serum and BALf galactomannan LFA for diagnosing IAA. Our findings will allow us to develop strategies for rapidly and accurately identifying patients with IAA. This study addresses fundamental gaps in understanding of the epidemiology and clinical aspects of an under-appreciated form of invasive aspergillosis. It will lead to clinical trials in which improved understanding of IAA and its diagnosis are used to guide early antifungal treatment strategies, as well as to future laboratory studies of IAA pathogenesis. The project is feasible due to the multidisciplinary expertise of our collaborative team of pre-eminent physician- investigators. Finally, the study has the support of the US Centers for Disease Control and Prevention and a recently-formed international IAA consortium, relationships that will useful in designing and executing follow-up projects.

项目摘要 烟曲霉和其他曲霉属物种的侵袭性感染是死亡和感染的主要原因。 严重免疫抑制宿主的发病率。最近，侵袭性曲霉病被描述为 严重流感感染的并发症，主要发生在没有传统曲霉病风险的患者中 因素尽管流感相关曲霉病（IAA）的病例报告越来越多， 在美国，该病的临床特征尚不清楚。而曲霉病的危险因素 在免疫抑制人群中得到了很好的描述，但尚未在严重 流行性感冒在迄今为止规模最大的IAA研究中，研究人员回顾性地诊断了14%-19%的疾病。 2009- 2016年7家欧洲医院重症监护室（ICU）流感患者的死亡率; IAA为50%。在来自单个ICU的回顾性报告中描述了可比的发生率，但 在大多数严重流感的多中心研究中，曲霉菌双重感染较低。在没有 在严重流感患者中进行曲霉病的系统检测，IAA可能不足- 被美国临床医生认可，在文献中报告不足。与此同时， 在回顾性欧洲研究中，通过自由接受血清或支气管肺泡灌洗液（BALf） 半乳甘露聚糖作为疾病的决定性标志物。我们在这个项目中的目标是确定发病率，临床 特征，和危险因素的IAA进行了第一次前瞻性研究，在美国的疾病。我们将 采用严格的IAA病例定义和ICU系统的血清和BALf半乳甘露聚糖诊断检测 严重流感患者。我们假设，我们将证明美国的IAA率 与欧洲报告的结果相当，并且一种新的即时半乳甘露聚糖侧流测定（LFA） 将显示出诊断IAA的强敏感性和特异性。在目标1中，我们将进行前瞻性的， 在美国不同地区的4个大型医疗中心的ICU中进行的IAA观察性临床研究。在目标2中， 我们将评估血清和BALf半乳甘露聚糖LFA诊断IAA的性能。我们的发现将 使我们能够制定快速准确识别IAA患者的策略。这项研究涉及 在了解流行病学和临床方面的基本差距， 侵袭性曲霉病这将导致临床试验，其中提高对IAA及其诊断的理解， 用于指导早期抗真菌治疗策略，以及未来IAA发病机制的实验室研究。 该项目是可行的，由于我们的合作团队的多学科专业知识的杰出医生- investigators.最后，这项研究得到了美国疾病控制和预防中心的支持， 最近成立的国际宇航科学院联合会，这种关系将有助于设计和执行后续行动 项目