Airway pH regulation in asthma
哮喘气道 pH 值调节
基本信息
- 批准号:10662247
- 负责人:
- 金额:$ 39.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectAgonistAmmoniaAnatomyAndrogensAsthmaAttenuatedBicarbonatesBuffersCarbon DioxideCell Culture TechniquesCell surfaceCystic FibrosisDistalEnzymesEpithelial CellsEpitheliumExhalationFunctional disorderGlucocorticoidsGlutaminaseHealthHumanIL17 geneIL6 geneIn VitroInflammationInflammatoryInhalationInterleukin-13Interleukin-4KidneyLactate DehydrogenaseLiquid substanceLocationMapsMeasuresMembraneMetabolismOxidasesOxidoreductasePatientsProductionProteinsProtonsRegulationRespiratory Tract InfectionsS-NitrosoglutathioneSurfaceTestingTubular formationVariantViralairway epitheliumairway inflammationalveolar lamellar bodyasthma exacerbationasthmatic airwayasthmatic patientbeta-2 Adrenergic Receptorscarbonate dehydratasecell growth regulationcytokinedehydroepiandrosteroneexperiencefallsgenetic regulatory proteinimprovedin vivoinjured airwayinnovationnovel strategiespersonalized approachprotein expressionresponsevacuolar H+-ATPasevoltage
项目摘要
PROJECT SUMMARY/ABSTRACT
Project 2
The airway epithelium, like the renal tubular epithelium, expresses proteins that regulate luminal pH. For
example, glutaminase regulates ammonia production; it is inhibited by Th1 cytokines, acidifying the airway.
Cystic fibrosis transmembrane regulatory protein regulates outward HCO3- transit, and its absence results in
luminal acidification. Decreased airway lining fluid pH can promote airway inflammation as well as viral and
bacterial replication. We hypothesize that the distal airway epithelial surface is acidic, both because of high CO2
levels and low- pH lamellar bodies; that pH increases as airway lining fluid is swept proximally; and that impaired
airway luminal buffering can contribute to the pathophysiology of asthma. In particular, there is evidence that
acute asthma exacerbations are associated with a fall in airway luminal pH; an effect reversed by glucocorticoids.
Further, some asthma patients have a low luminal pH at baseline. Here, we will study the cellular determinants
of airway pH regulation. We will make use of the effect of airway pH to alter airway NO metabolism and
bioactivities (Project 1) to map the location and effects of low pH in the asthmatic airway in vivo. We will study
the recently discovered effects of androgens (Project 3) to promote the expression of beneficial pH regulatory
enzymes in asthma. Finally, we will study the potential benefit of inhaled buffer in asthma patients with
exacerbations. Specifically, we will carry out three aims.
In Aim 1, we will characterize the cellular determinants of airway pH. In Aim 2, we will map the epithelial pH of
the normal and asthmatic airway. In Aim 3, we will measure the effect of inhaled buffer on inflammation and
response to β2 agonists in asthma. At the end of the project, we anticipate having mapped both the cellular
regulation of airway epithelial pH and the anatomic variations in airway pH in health and in asthma; and we will
have developed a new, personalized approach to target pH abnormalities in patients with asthma exacerbations.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Benjamin Gaston其他文献
Benjamin Gaston的其他文献
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{{ truncateString('Benjamin Gaston', 18)}}的其他基金
Indiana Medical Scientist/Engineer Training Program
印第安纳州医学科学家/工程师培训计划
- 批准号:
10555556 - 财政年份:2023
- 资助金额:
$ 39.63万 - 项目类别:
Scientific innovation for personalized severe asthma management
个性化重症哮喘管理的科学创新
- 批准号:
10269966 - 财政年份:2021
- 资助金额:
$ 39.63万 - 项目类别:
Scientific innovation for personalized severe asthma management
个性化重症哮喘管理的科学创新
- 批准号:
10662235 - 财政年份:2021
- 资助金额:
$ 39.63万 - 项目类别:
Scientific innovation for personalized severe asthma management
个性化重症哮喘管理的科学创新
- 批准号:
10457990 - 财政年份:2021
- 资助金额:
$ 39.63万 - 项目类别:
Sudaxine as an analgesia sparing respiratory stimulant for use in critical care
Sudaxine 作为一种镇痛、省呼吸兴奋剂,用于重症监护
- 批准号:
10505268 - 财政年份:2020
- 资助金额:
$ 39.63万 - 项目类别:
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