Structural Determinants of Disease Progression in COPD
Structural Determinants of Disease Progression in COPD
批准号:
10374005
负责人:
Surya P. Bhatt
金额:
$51.9万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-04-05 至 2025-03-31
关键词:
3-DimensionalAdultAffectAlveolarAnatomyAreaAttenuatedCaliberCause of DeathChronic Obstructive Pulmonary DiseaseClinicalComplexConsumptionCross-Sectional StudiesDataDevelopmentDimensionsDiseaseDisease ProgressionEnrollmentEuclidean SpaceFractalsGrowthHeterogeneityImageIndividualInflammationLungMeasuresMechanicsModelingOutcome MeasurePathway interactionsPharmaceutical PreparationsPharmacotherapyPhenotypeProcessPulmonary EmphysemaPulmonary Function Test/Forced Expiratory Volume 1ScanningSeveritiesShapesSmoking StatusSpatial DistributionStretchingSurrogate MarkersTestingTherapeuticThickTimeUnited StatesX-Ray Computed Tomographyairway obstructionairway remodelingalveolar destructionbaseclinical predictorscohortfollow-upgenetic epidemiologyhigh riskimaging biomarkerindexinginflammatory lung diseaseinsightmortalitymouse modelnovelpersonalized diagnosticspulmonary function declinerespiratory morbiditytargeted treatment
中文摘要
项目摘要/摘要
慢性阻塞性肺疾病(COPD)是一种肺部炎症性疾病,导致
气流受限;它影响着美国2400万成年人,是第三大死亡原因。近期
研究挑战了COPD是一致进展性的这一范式,但其基础机制不同
疾病进展的轨迹还没有被很好地理解。治疗进展的一个主要障碍是
改变疾病进展的是我们无法准确地对具有不同疾病轨迹的个体进行表型;
缺乏可靠的替代生物标记物来预测个体受试者的临床进展。此外,现有的
药物治疗对呼吸道发病率的影响不大,但不能影响FEV1的下降率。
这些药物针对的是气道张力和炎症,没有一种直接针对涉及
导致FEV1改变的呼吸道或肺泡重塑(肺气肿)。因此,理解上的一个主要差距是
确定决定疾病的结构性气道/肺泡重塑的相互依赖的途径
进展,这将为COPD的更准确的诊断和治疗策略提供信息。
慢性阻塞性肺疾病的起源被认为是直径小于2毫米的小传导气道,但这些
数据大多是横截面的。此外,慢性阻塞性肺疾病的特征是呼吸道重构和肺泡重构。
破坏;这两个过程很可能都促成了疾病的开始和发展。我们的初步调查结果
提示疾病的进展是由于肺部结构变化的复杂相互作用而发生的,无论是在
包括正常肺实质的机械拉伸,肺气肿的分布,
和呼吸道重塑。FEV1的变化和结构性疾病的进展不能完全反映疾病的进展
疾病是疾病轨迹的重要决定因素。基于这些发现,我们假设结构性的
呼吸道和肺泡腔内的解剖和机械因素在疾病进展中起作用
慢性阻塞性肺疾病(慢阻肺)。
为了验证这些假设,我们将分析来自两个特征良好的大型队列(Genetic
COPD研究中COPD、COPD基因、亚群和中间结局指标的流行病学,
SPIROMICS),并进行为期5年的随访,具体目标如下。此应用程序的目标1将是确定
机械影响肺是否导致肺气肿的发生和发展。在目标2中,我们将确定
肺气肿的空间分布是否影响疾病的进展。在目标3中,我们将确定是否
气道重塑的纵向变化与肺功能下降有关。
这些结果将确定疾病进展的机制,建立新的成像生物标记物,并有助于
创建精确的模型,以便开发更有针对性的治疗方法来减缓疾病的进展。
英文摘要
Project Summary/ Abstract
Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lungs that results in
airflow limitation; it affects 24 million adults in the United States, and is the third leading cause of death. Recent
studies challenge the paradigm that COPD is uniformly progressive, but the mechanisms that underlie distinct
trajectories of disease progression are not well understood. A major hurdle in the advancement of therapies that
alter the progression of disease is our inability to precisely phenotype individuals with variable disease trajectories;
reliable surrogate biomarkers to predict clinical progression in individual subjects are lacking. Furthermore, existing
pharmacotherapies have a modest impact on respiratory morbidity and fail to impact the rate of FEV1 decline.
These medications target airway tone and inflammation, and none directly target structural changes involving the
airways or alveolar remodeling (emphysema) that underlie FEV1 change. Thus, a major gap in understanding is
the identification of inter-dependent pathways of structural airway/alveolar remodeling that determine disease
progression which would inform more precise diagnostic and therapeutic strategies for COPD.
The origins of COPD are believed to be in the small conducting airways less than 2 mm in diameter but these
data are mostly cross-sectional. In addition, COPD is characterized by both airway remodeling and alveolar
destruction; it is likely that both processes contribute to disease initiation and progression. Our preliminary findings
suggest that disease progression occurs due to a complex interplay of structural changes in the lungs, both in the
parenchyma and in the airways, including mechanical stretch of normal parenchyma, distribution of emphysema,
and airway remodeling. Disease progression is not reflected entirely by FEV1 changes and progression of structural
disease is an important determinant of disease trajectory. Based on these findings, we hypothesize that structural
anatomic and mechanical factors in both the airway and alveolar compartments contribute to disease progression in
COPD.
To test these hypotheses, we will analyze data from two large well-characterized cohorts (Genetic
Epidemiology of COPD, COPDGene, and Subpopulations and Intermediate Outcome Measures in COPD Study,
SPIROMICS) with 5-year follow-up with the following specific aims. Aim 1 of this application will be to determine
whether mechanically affected lung leads to initiation and progression of emphysema. In Aim 2, we will determine
whether the spatial distribution of emphysema influences disease progression. In Aim 3, we will determine whether
longitudinal changes in airway remodeling are associated with lung function decline.
The results will identify mechanisms of disease progression, establish novel imaging biomarkers, and help
create precise models that will allow development of more targeted therapies to attenuate disease progression.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
1/2 Video Telehealth Pulmonary Rehabilitation to Reduce Hospital Readmission in Chronic Obstructive Pulmonary Disease (Tele-COPD)
-
批准号:10300304
-
项目类别:
-
资助金额:$153.71万
-
财政年份:2021
-
负责人:Surya P. Bhatt
-
依托单位:
1/2 Video Telehealth Pulmonary Rehabilitation to Reduce Hospital Readmission in Chronic Obstructive Pulmonary Disease (Tele-COPD)
-
批准号:10505270
-
项目类别:
-
资助金额:$180.22万
-
财政年份:2021
-
负责人:Surya P. Bhatt
-
依托单位:
Structural Determinants of Disease Progression in COPD
-
批准号:10593047
-
项目类别:
-
资助金额:$52.2万
-
财政年份:2020
-
负责人:Surya P. Bhatt
-
依托单位:
Deep Learning and Fluid Dynamics Based Phenotyping of Expiratory Central Airway Collapse
-
批准号:10013198
-
项目类别:
-
资助金额:$18.7万
-
财政年份:2019
-
负责人:Surya P. Bhatt
-
依托单位:
Diastolic Dysfunction and Pauci-inflammatory Acute Exacerbations of Chronic Obstructive Pulmonary Disease
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批准号:9981812
-
项目类别:
-
资助金额:$14.22万
-
财政年份:2016
-
负责人:Surya P. Bhatt
-
依托单位:
Assignment of "Diastolic Dysfunction and Pauci-inflammatory Acute Exacerbations of Chronic Obstructive Pulmonary Disease"
-
批准号:9163363
-
项目类别:
-
资助金额:$19.48万
-
财政年份:2016
-
负责人:Surya P. Bhatt
-
依托单位:
Diastolic Dysfunction and Pauci-inflammatory Acute Exacerbations of Chronic Obstructive Pulmonary Disease
-
批准号:9753343
-
项目类别:
-
资助金额:$19.48万
-
财政年份:2016
-
负责人:Surya P. Bhatt
-
依托单位:
海外基金