Pneumonia Biology
Pneumonia Biology
批准号:
10320737
负责人:
JOSEPH P MIZGERD
金额:
$83.88万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-01-11 至 2023-12-31
关键词:
AcuteAddressAdultAffectAgeAgingAlveolar MacrophagesAwardBacteriaBiologyCardiovascular DiseasesChildChronic DiseaseChronic lung diseaseCoupledDefense MechanismsDevelopmentDiseaseElderlyEpithelial CellsGrantImmune responseIncidenceIndividualLungLung diseasesLung infectionsMediatingMicrobeMorbidity - disease rateNational Heart, Lung, and Blood InstituteNatural ImmunityOrganismPneumoniaPredispositionPulmonary InflammationResearchRespiratory FailureRoleVirulenceVirusacute infectionadaptive immunityburden of illnessmicrobialmiddle agemortalitymortality risknovel strategiespathobiontpreventprogramsrespiratory
中文摘要
摘要
肺炎生物学应该是NHLBI R35的重点。肺炎是全球主要的
疾病在每一项分析中。它在世界范围内杀死了更多的儿童,让更多的美国儿童住院治疗
其他疾病。老年人受到的影响更大。肺炎的发病率和死亡风险增加
在整个成年期,直到变成比年幼儿童大几个数量级。但一想到
成年人必须年老体弱才能患上肺炎,这是一个适得其反的误解。肺炎
易感性在中年明显,美国成年人的中位数年龄没有免疫功能受损
因肺炎住院57年。除了直接可归因于即时发病率和
死亡率、肺炎还会加速不健康的衰老,包括病情恶化和更快的下降
慢性肺部疾病、心血管疾病等等。各种各样的病毒,
细菌和其他微生物导致肺炎,没有一种微生物对多达十分之一的
案子。这与微生物无关。这些是病原体,不是病原体。它们在我们中间流传
反复或不断地生活在我们身上,只有在异常情况下才会在肺中生长而引起肺炎
情况。肺炎是否接踵而至,取决于宿主反应的质量和数量。
肺炎更多的是由于肺防御的失败,而不是微生物的毒力。我们需要了解
在我们能够识别、预防或预防肺炎之前,通常预防年轻健康成年人肺炎的肺防御系统
扭转使个人更容易感染肺炎的错误。我们正在进行的研究计划是
解决肺炎的肺防御问题,长期和持续的重点是
肺部炎症和先天免疫,现在加上对自然获得性免疫的新强调
针对呼吸道病原体的异型适应性免疫。这项研究计划包括2个正在进行的
定义肺上皮细胞和肺泡巨噬细胞在介导保护中的作用的NHLBI R01
对抗肺炎。这两笔赠款加起来总共26 R01年来自NHLBI的支持,我们建议
将我们成熟而富有成效的研究计划的这些不同组成部分统一到更完整的R35中
获奖。在接下来的几年里,我们设想我们的研究计划(I)促进对机械的理解
肺成分与适应性功能整合在肺防御肺炎中的作用
免疫,(2)利用肺防御方面的发现,产生新的预防和治疗方法
肺炎,以及(Iii)推广肺炎易感性是一种慢性衰老疾病的概念,以及
攻击易感机制而不是(或除了)急性感染是最大的
承诺减轻这种肺部疾病的负担。
英文摘要
Abstract
Pneumonia biology should be the focus of an R35 from the NHLBI. Pneumonia is a leading global burden of
disease in every analysis. It kills more children worldwide and hospitalizes more US children than does any
other disease. Older adults are even more affected. The incidence and risk of death from pneumonia increase
throughout adulthood until becoming orders of magnitude greater than for young children. But the idea that
adults have to be old and frail to get pneumonia is a counter-productive misconception. Pneumonia
susceptibility is pronounced in middle age, with the median age of non-immunocompromised US adults
hospitalized for pneumonia being 57 years. In addition to the directly attributable immediate morbidity and
mortality, pneumonia also accelerates unhealthy aging, including exacerbations and more rapid decline of
chronic pulmonary diseases, cardiovascular diseases, and more. A wide ranging assortment of viruses,
bacteria, and other microbes causes pneumonia, with no one organism responsible for as much as a tenth of
cases. It is not about the microbe. These are pathobionts, not pathogens. They circulate among us
repeatedly or live on us continuously, growing in the lung to cause pneumonia only under exceptional
circumstances. Whether pneumonia ensues depends on the quality and quantity of the host response.
Pneumonia results from failures of lung defense more than from microbial virulence. We need to understand
the lung defenses that normally prevent pneumonia in young healthy adults before we can identify, prevent, or
reverse what goes wrong to make individuals susceptible to pneumonia. Our ongoing research program is
addressing the question of lung defense against pneumonia with a long-standing and continuing focus on
pulmonary inflammation and innate immunity that is now coupled with a newer emphasis on naturally acquired
heterotypic adaptive immunity against respiratory pathobionts. This research program includes 2 ongoing
NHLBI R01s that are defining roles of lung epithelial cells and alveolar macrophages in mediating protection
against pneumonia. These 2 grants together total 26 R01-years of support from the NHLBI, and we propose
unifying these distinct components of our mature and productive research program into a more integrated R35
award. During the coming years, we envision our research program (i) advancing mechanistic understanding
of lung defense against pneumonia by functionally integrating the activities of lung constituents and adaptive
immunity, (ii) leveraging discoveries in lung defense to generate new approaches to preventing and curing
pneumonia, and (iii) forwarding the concept that pneumonia susceptibility is a chronic disease of aging, and
attacking the mechanisms of susceptibility rather than (or in addition to) the acute infection has the greatest
promise for diminishing the burden of this lung disease.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Pulmonary pathophysiology sub-phenotypes of pneumonia
-
批准号:10559704
-
项目类别:
-
资助金额:$82.3万
-
财政年份:2022
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Pulmonary pathophysiology sub-phenotypes of pneumonia
-
批准号:10446020
-
项目类别:
-
资助金额:$85.63万
-
财政年份:2022
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Pneumonia Biology
-
批准号:10543425
-
项目类别:
-
资助金额:$83.88万
-
财政年份:2017
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Pneumonia Biology
-
批准号:10225230
-
项目类别:
-
资助金额:$71.65万
-
财政年份:2017
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Lung-resident antibacterial heterotypic immunity
-
批准号:10646277
-
项目类别:
-
资助金额:$46.73万
-
财政年份:2015
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Lung-resident antibacterial heterotypic immunity
-
批准号:8986378
-
项目类别:
-
资助金额:$40.93万
-
财政年份:2015
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Lung-resident antibacterial heterotypic immunity
-
批准号:9927559
-
项目类别:
-
资助金额:$48.72万
-
财政年份:2015
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Lung-resident antibacterial heterotypic immunity
-
批准号:9295936
-
项目类别:
-
资助金额:$40.93万
-
财政年份:2015
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Lung-resident antibacterial heterotypic immunity
-
批准号:10183144
-
项目类别:
-
资助金额:$48.12万
-
财政年份:2015
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Lung-resident antibacterial heterotypic immunity
-
批准号:10447212
-
项目类别:
-
资助金额:$47.51万
-
财政年份:2015
-
负责人:JOSEPH P MIZGERD
-
依托单位:
2008 Biology of Acute Respiratory Infections Gordon Research Conference
-
批准号:7391507
-
项目类别:
-
资助金额:$1.1万
-
财政年份:2007
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Regulation and function of STAT3 during pneumonia
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批准号:6968007
-
项目类别:
-
资助金额:$41.0万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Regulation and function of STAT3 during pneumonia
-
批准号:7232094
-
项目类别:
-
资助金额:$38.88万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Cytokine-stimulated systemic defenses during pneumococcal pneumonia
-
批准号:8250351
-
项目类别:
-
资助金额:$41.02万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Cytokine-stimulated systemic defenses during pneumococcal pneumonia
-
批准号:8645682
-
项目类别:
-
资助金额:$39.8万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Cytokine-stimulated systemic defenses during pneumococcal pneumonia
-
批准号:8444454
-
项目类别:
-
资助金额:$38.95万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Regulation and function of STAT3 during pneumonia
-
批准号:7433135
-
项目类别:
-
资助金额:$38.52万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Regulation and function of STAT3 during pneumonia
-
批准号:7647919
-
项目类别:
-
资助金额:$38.52万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Cytokine-stimulated systemic defenses during pneumococcal pneumonia
-
批准号:8107055
-
项目类别:
-
资助金额:$41.02万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
Cytokine-stimulated systemic defenses during pneumococcal pneumonia
-
批准号:8821645
-
项目类别:
-
资助金额:$39.72万
-
财政年份:2005
-
负责人:JOSEPH P MIZGERD
-
依托单位:
海外基金