Fungal Translocation in Chronic Obstructive Pulmonary Disease
慢性阻塞性肺疾病中的真菌移位
基本信息
- 批准号:10434243
- 负责人:
- 金额:$ 77.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-15 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAirAntiinflammatory EffectApicalAttenuatedBacteriaBacterial TranslocationBindingBlood CirculationCCL2 geneCCL20 geneCXCL10 geneCXCL5 geneCell WallCellsCellular StructuresChronic Obstructive Pulmonary DiseaseClinicalClinical TrialsDataDendritic CellsDiseaseDisease MarkerDisease OutcomeDisease ProgressionEphA2 ReceptorEpithelialEpithelial CellsExerciseExposure toFoundationsFrequenciesFungal ComponentsFutureHumanHypoxiaIL8 geneImmuneImmune responseImmunoassayImpairmentIn VitroInflammationInflammation MediatorsInflammatoryInterleukin-6Intestinal MucosaIntestinal permeabilityIntestinesLactuloseLeadLiquid substanceLungMacrophage ActivationMannitolMeasuresMediatingMediationMediator of activation proteinMetforminMicrobeMolecularMovementMycosesOrganismOutcomePathogenesisPathogenicityPatientsPatternPattern recognition receptorPeripheralPhysical activityPlayPolysaccharidesProtein SecretionProteinsPulmonary EmphysemaRespiratory Signs and SymptomsRestReverse Transcriptase Polymerase Chain ReactionRisk FactorsRoleSeverity of illnessSmall Interfering RNASmokerSmokingSymptomsTNF geneTestingTissuesValidationWestern Blottingabsorptionbronchial epitheliumchest computed tomographycigarette smokecohortcytokinedectin 1experimental studyexposure to cigarette smokefollow-upformer smokerfunctional declinegastrointestinal epitheliumgut-lung axisimmune activationimprovedindexinginsightknock-downlaminaranlung injurymRNA Expressionmacrophagemicrobialnovel strategiesnovel therapeutic interventionnovel therapeuticspathogenpolyglucosanprospectivepulmonary functionpulmonary function declinerespiratoryrespiratory morbiditysmall molecule inhibitorsugartargeted treatment
项目摘要
PROJECT SUMMARY
Although smoking is a leading risk factor for chronic obstructive pulmonary disease (COPD), other factors likely
contribute to disease pathogenesis since only a subset of smokers develop COPD. Tissue hypoxia related to
acute exacerbations or physical activity impairs gut epithelial barrier function in COPD and may result in microbial
translocation, or movement of microbes or microbial products across the intestinal mucosa. Once in circulation,
these microbial products may cause immune cell activation or direct lung injury, augmenting inflammation and
lung function decline in patients with COPD. Although studies of microbial translocation have largely focused on
the translocation of bacteria, we have preliminary data suggesting that fungal translocation occurs in smokers
and may contribute to COPD pathogenesis. We show that 1,3 beta-d-glucan (BDG), a pattern associated
molecular pattern that is a major polysaccharide component of the fungal cell wall, is elevated in COPD patients
in the absence of invasive fungal infection and correlates with lung function, symptoms, and exacerbations. In
vitro, BDG increases lung epithelial cell expression of inflammatory cytokines involved in the pathogenesis of
COPD. With this project, we will test the overarching hypothesis that impaired gut epithelial barrier integrity in
COPD patients leads to fungal microbial translocation that contributes to lung function decline and worse
respiratory morbidity through heightened immune cell activation and direct lung pathogenic effects. Aim 1 will
assess the relationship between gut epithelial barrier integrity measured by the lactulose/mannitol differential
sugar absorption test, lung function, respiratory morbidity (symptoms, exacerbations), and circulating BDG levels
in a cohort of current and former smokers with COPD. Aim 2 will determine the association between circulating
BDG levels, immune cell activation, prospective exacerbations, and two-year change in lung function, symptoms,
and CT indices of emphysema and airways in COPD. Aim 3 will determine whether BDG increases cytokine
expression and secreted protein levels by binding to the lung epithelial cell pattern recognition receptors Dectin-
1 and EphA2 in human bronchial epithelial cells in vitro, and if this effect is potentiated by co-exposure to cigarette
smoke. Aim 3 will also investigate if BDG effects on cytokine expression and secreted protein levels are
attenuated by treatment with metformin. At the completion of this project, we will have gained critical insight into
the role of microbial translocation in COPD pathogenesis and will have built the foundation for future clinical trials
targeting the gut-lung axis by either improving gut epithelial barrier function, blocking BDG’s actions, or
modulating BDG’s downstream effects as a novel approach to therapy in COPD.
项目总结
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JESSICA BON其他文献
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{{ truncateString('JESSICA BON', 18)}}的其他基金
Fungal Translocation in Chronic Obstructive Pulmonary Disease
慢性阻塞性肺疾病中的真菌移位
- 批准号:
10610446 - 财政年份:2022
- 资助金额:
$ 77.57万 - 项目类别:
Pittsburgh Innovation in Collaborative Training of Residents Alliance
匹兹堡居民联盟协作培训创新
- 批准号:
10608088 - 财政年份:2020
- 资助金额:
$ 77.57万 - 项目类别:
Pittsburgh Innovation in Collaborative Training of Residents Alliance
匹兹堡居民联盟协作培训创新
- 批准号:
10350563 - 财政年份:2020
- 资助金额:
$ 77.57万 - 项目类别:
The impact of a home-based pulmonary telerehabilitation program on muscle function and quality of life following acute exacerbations of chronic obstructive pulmonary disease
家庭肺远程康复计划对慢性阻塞性肺疾病急性加重后肌肉功能和生活质量的影响
- 批准号:
10201778 - 财政年份:2019
- 资助金额:
$ 77.57万 - 项目类别:
Autoimmunity and emphysema and risk of osteoporosis in smokers
吸烟者的自身免疫和肺气肿以及骨质疏松症的风险
- 批准号:
9916794 - 财政年份:2016
- 资助金额:
$ 77.57万 - 项目类别:
Emphysema and Inflammatory Biomarkers and Risk of Osteoporosis in Men with COPD
肺气肿和炎症生物标志物以及男性慢性阻塞性肺病患者骨质疏松症的风险
- 批准号:
9551566 - 财政年份:2015
- 资助金额:
$ 77.57万 - 项目类别:
Emphysema and Inflammatory Biomarkers and Risk of Osteoporosis in Men with COPD
肺气肿和炎症生物标志物以及男性慢性阻塞性肺病患者骨质疏松症的风险
- 批准号:
9932924 - 财政年份:2015
- 资助金额:
$ 77.57万 - 项目类别:
Emphysema and Inflammatory Biomarkers and Risk of Osteoporosis in Men with COPD
肺气肿和炎症生物标志物以及男性慢性阻塞性肺病患者骨质疏松症的风险
- 批准号:
9337253 - 财政年份:2015
- 资助金额:
$ 77.57万 - 项目类别:
The Relationship Between Osteoporosis and Phenotypic Heterogeneity in COPD
骨质疏松症与慢性阻塞性肺病表型异质性的关系
- 批准号:
7903213 - 财政年份:2009
- 资助金额:
$ 77.57万 - 项目类别:
The Relationship Between Osteoporosis and Phenotypic Heterogeneity in COPD
骨质疏松症与慢性阻塞性肺病表型异质性的关系
- 批准号:
8309992 - 财政年份:2009
- 资助金额:
$ 77.57万 - 项目类别:
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