Hypercoagulability and Chronic Lung Disease in Older Adults
老年人的高凝状态和慢性肺病
基本信息
- 批准号:9764481
- 负责人:
- 金额:$ 17.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-01 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdultAnticoagulantsAsthmaBiologicalBiological TestingBloodBlood VesselsBlood flowCD40 LigandCardiovascular DiseasesCardiovascular systemCause of DeathChronicChronic BronchitisChronic Obstructive Airway DiseaseChronic lung diseaseClinicalClinical ResearchClinical TrialsCoagulation ProcessCohort StudiesCross-Over StudiesCross-Sectional StudiesDataDevelopmentDiseaseElderlyEmbolismEnvironmentEnvironmental sludgeEpidemiologistEpidemiologyEtiologyEventFactor VIIIFibrinogenFundingGeneral PopulationGeneticGenomicsGenotypeGoalsHemostatic AgentsHospitalizationHypoxemiaHypoxiaImageImaging TechniquesInflammationInstitutesInstructionInternationalInternistLongitudinal StudiesLungMagnetic Resonance AngiographyMeasurementMeasuresMentorsMentorshipMethodsMicrovascular DysfunctionMorbidity - disease rateMulti-Ethnic Study of AtherosclerosisNational Heart, Lung, and Blood InstituteOperations ResearchOutcomeParticipantPathogenesisPathway interactionsPatient RecruitmentsPatientsPerfusionPersonsPhase II Clinical TrialsPhenotypePlasminogen Activator Inhibitor 1Positioning AttributePredictive FactorPreventionPrevention therapyPrimary PreventionProtein CProtocols documentationPublicationsPublishingPulmonary EmphysemaRandomizedResearchResearch PersonnelResourcesRespiratory Signs and SymptomsRespiratory physiologyRiskRisk FactorsRisk stratificationRoleSamplingSecondary PreventionSeveritiesSmokerSmokingSupervisionSurrogate EndpointTestingThrombomodulinThrombophiliaTrainingTraining ActivityUnited States National Institutes of HealthUniversitiesWorkadjudicateadjudicationapprenticeshipasthma exacerbationbasecareercareer developmentclinically relevantcohortdisease diagnosisdisease phenotypedisorder preventiondisorder riskendothelial dysfunctionexperiencefollow-upfunctional declinegenetic epidemiologyhigh riskimprovedinnovationinstrumentlung imagingmodifiable riskmortalitymultidisciplinarynoveloperationpopulation basedprogramsprotein biomarkersrecruitrespiratorytargeted treatment
项目摘要
Project Summary/Abstract
Rationale: Chronic lung disease (CLD) is the third leading cause of death in the US. Exacerbations, defined by
an increase in respiratory symptoms, are the major driver of morbidity and mortality for the frequently
overlapping “obstructive” CLD phenotypes of chronic obstructive pulmonary disease (COPD), emphysema,
chronic bronchitis and asthma. An improved understanding of modifiable risk factors for CLD exacerbations is
urgently needed, and – as demonstrated by advances in cardiovascular research – a focus on clinical events
may support advances in primary prevention of CLD, a priority for the NHBLI Lung Division. To date, options
for risk stratification with respect to incident CLD and exacerbations remain limited in the general population,
as the majority of prior CLD studies have studied exacerbations only in persons with established disease.
Candidate: The candidate is a general internist at Columbia University (CU) and doctoral candidate in
Epidemiology. Building upon her publication on subclinical emphysema in the general population as an
independent predictor of all-cause mortality, she has developed a protocol to define and adjudicate CLD
events for epidemiologic/primary prevention studies. She is applying this protocol in a six-cohort consortium,
which she is currently building to study novel risk factors for CLD events. Her long-term career goal is to
develop an independent, cross-disciplinary research program leveraging respiratory epidemiology, genomics
and imaging to identify biological pathways that may be targeted in order to achieve primary and secondary
prevention of CLD exacerbations. Career Development: The candidate's short-term objectives are to
complete her epidemiology doctoral training and to obtain formal training in genomics, individualized instruction
in advanced pulmonary imaging techniques, and apprenticeship in the operations of clinical research, while
receiving ongoing multidisciplinary mentorship from internationally-recognized leaders in respiratory
epidemiology, genomics, magnetic resonance angiography, and clinical research. Environment: CU has
abundant resources to support this application including its NIH-CTSA funded Irving Institute for Clinical
Research. Research: The proposed research will test biologically plausible hypotheses on how
hypercoagulability may represent a biological target for primary and secondary prevention efforts, while also
leveraging resources unique to the candidate and providing relevant and career-stage appropriate training to
promote her development into an independent investigator. Rates of pulmonary emboli are substantially
increased in CLD and exacerbations; nonetheless, the extent to which hypercoagulability is a cause, an effect,
or a correlate of CLD is unknown. A causal role for hypercoagulability in CLD is supported by recent findings
suggesting that hypoxemia promotes hypercoagulability, that pulmonary perfusion is altered in COPD and
exacerbations, and by pilot work from the PI that is highly supportive of the main aims. Aims 1A and 1B will
test whether elevated levels of hemostatic factors independently predict incident CLD and incident
exacerbations in a case-cohort study nested in the Multi-Ethnic Study of Atherosclerosis (MESA) and a multi-
cohort pooled sample developed by the candidate, using methods enriched by the candidate's doctoral
training, and cohorts with which she has gained considerable experience working. Aim 1C builds upon her
prior experience in genetic epidemiology and proposed genomics training to examine whether genetically
estimated hemostatic factors are associated with incident CLD events and longitudinal decline in lung function
in the same pooled sample. Clinical endpoints will be classified according to an innovative adjudication
protocol developed and validated by the candidate. Confirmation of Aim 1 hypotheses would provide a novel
CLD risk score for risk stratification in the general population as well as a biological target for CLD prevention
and treatment with anticoagulants. Aim 2 will examine alterations in pulmonary perfusion as a mechanism by
which hypercoagulability and sludging may relate to CLD pathogenesis and exacerbations. In Aim 2A, the
candidate will coordinate, supervise and analyze pulmonary magnetic resonance angiography (MRA) images
for the measurement of pulmonary microvascular blood flow (PMBF), a measure developed by the Mentor and
Advisor, during and six weeks following acute CLD exacerbation for 30 participants that she will recruit from an
existing cohort. Completion of Aim 2A will reinforce training activities in pulmonary imaging and clinical
research operations, and will test the hypotheses that PMBF is acutely diminished in exacerbations compared
to baseline; that these differences will persist at six weeks later; and that these changes in PMBF will be
correlated with concurrently measured hemostatic factors. In Aim 2B, the candidate will test if hemostatic
factors are associated with change in PMBF over five years of follow-up in stable COPD and emphysema.
Results from Aim 1 will provide a risk score to support an R01 application on prevention in existing NHLBI
cohorts. Aim 2 will provide pilot data to support an R01 on hemostatic factor and pulmonary MRA phenotyping
of exacerbations in a larger cohort, and potentially an application for a Phase 2 clinical trial of anticoagulants in
persons at high risk for exacerbation, using PMBF as an intermediate phenotype. Hence, completion of the
proposed training and scientific aims would position the PI as a respiratory epidemiologist with a
unique level of epidemiology, genomics, and imaging training, one or more clinically relevant R01-
funded projects, and a commitment to research in primary and secondary prevention of CLD.
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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Elizabeth Oelsner其他文献
Elizabeth Oelsner的其他文献
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{{ truncateString('Elizabeth Oelsner', 18)}}的其他基金
Metal Exposure and Subclinical Lung Disease in Adult E-cigarette Users
成人电子烟使用者的金属接触和亚临床肺病
- 批准号:
10352389 - 财政年份:2021
- 资助金额:
$ 17.16万 - 项目类别:
COVID-19 Lung Microvascular and Parenchymal Sequelae (Lung-MaPS)
COVID-19 肺微血管和实质后遗症 (Lung-MaPS)
- 批准号:
10185337 - 财政年份:2021
- 资助金额:
$ 17.16万 - 项目类别:
COVID-19 Lung Microvascular and Parenchymal Sequelae (Lung-MaPS)
COVID-19 肺微血管和实质后遗症 (Lung-MaPS)
- 批准号:
10614017 - 财政年份:2021
- 资助金额:
$ 17.16万 - 项目类别:
COVID-19 Lung Microvascular and Parenchymal Sequelae (Lung-MaPS)
COVID-19 肺微血管和实质后遗症 (Lung-MaPS)
- 批准号:
10448304 - 财政年份:2021
- 资助金额:
$ 17.16万 - 项目类别:
Metal Exposure and Subclinical Lung Disease in Adult E-cigarette Users
成人电子烟使用者的金属接触和亚临床肺病
- 批准号:
10570960 - 财政年份:2021
- 资助金额:
$ 17.16万 - 项目类别:
Respiratory health and cigar and pipe use in the NHLBI Pooled Cohorts Study
NHLBI 联合队列研究中的呼吸系统健康以及雪茄和烟斗的使用
- 批准号:
10224337 - 财政年份:2020
- 资助金额:
$ 17.16万 - 项目类别:
Respiratory health and cigar and pipe use in the NHLBI Pooled Cohorts Study
NHLBI 联合队列研究中的呼吸系统健康以及雪茄和烟斗的使用
- 批准号:
10037747 - 财政年份:2020
- 资助金额:
$ 17.16万 - 项目类别:
Hypercoagulability and Chronic Lung Disease in Older Adults
老年人的高凝状态和慢性肺病
- 批准号:
9180241 - 财政年份:2016
- 资助金额:
$ 17.16万 - 项目类别:
Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study
电子烟的通气和肺内皮毒性 (VaPE-Tox):随机交叉试点研究
- 批准号:
9130400 - 财政年份:2016
- 资助金额:
$ 17.16万 - 项目类别:
Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study
电子烟的通气和肺内皮毒性 (VaPE-Tox):随机交叉试点研究
- 批准号:
9327685 - 财政年份:2016
- 资助金额:
$ 17.16万 - 项目类别:
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