STRUCTURAL MECHANISMS OPERATING IN UNRESPONSIVE ASTHMA
无反应性哮喘的结构机制
基本信息
- 批准号:6638541
- 负责人:
- 金额:$ 32.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-06-01 至 2005-05-31
- 项目状态:已结题
- 来源:
- 关键词:asthma basement membrane bronchomotion clinical research computed axial tomography disease /disorder etiology elasticity extracellular matrix glucocorticoids growth /development human subject inflammation respiratory airflow disorder respiratory airway volume respiratory disorder chemotherapy respiratory epithelium
项目摘要
DESCRIPTION (Adapted from the applicant's abstract): Asthma is a chronic
disease that is actually composed of a broad spectrum of clinically defined
subgroups, rather than a single disease entity. Asthma is characterized by
structural and morphologic changes that affect airway stiffness. The
relationship of airway remodeling, airway stiffness, and airway distensibility
may be different for each of these subtypes. Although all subtypes suffer from
airway hyperresponsiveness, with acute exacerbations, there is a significant
subgroup of moderate to severe asthmatics who suffer with debilitating chronic
persistent obstruction despite frequent medication adjustments; i.e., the
disease is "unresponsive" to treatment. The objective of this proposal is to
determine the mechanisms underlying this chronic persistent obstruction in
moderate to severe asthmatic patients. Airways from normal subjects dilate with
each inspiration. This normal dilation is essential to distend airway smooth
muscle and maintain airway patency. In asthmatic subjects, however, this normal
dilating effect of inspiration may be compromised, leading to both acute and
chronic airflow obstruction. The investigators hypothesize that this
unresponsiveness results from structural changes in the airway wall that lead
to increased stiffness of the airway. Increased airway stiffness could occur
for several reasons. One explanation includes thickening and shortening of the
relatively indistensible mucosal basement membrane. Even in mild asthmatics
early in the development of the disease, there are changes in the basement
membrane and mucosa. These changes include specific structural alterations of
the airway wall extracellular matrix with the deposition of collagen,
fibronectin, and tenascin. Neither the reversibility of these changes nor their
functional consequences are well understood. This study will identify and
characterize the decreased airway distensibility that results from structural
changes in the airway wall, which may be an important mechanism that causes
unresponsive asthma. To measure airway distensibility, the investigators will
use high resolution computed tomography (HRCT), a unique noninvasive radiologic
technique, that will allow measurement of changes in airway size with lung
inflation in vivo. In addition, the structural composition of conducting airway
mucosa, and specific inflammatory mediators which may be responsible for
subsequent structural changes, obtained from endobronchial biopsies, will be
evaluated. Further, the effects of a clinically relevant intervention of oral
glucocorticoids on airway distensibility, and on the changes in the structure
of the extracellular matrix and specific inflammatory mediators, will be
measured. These studies will provide important new information regarding the
interaction between structural changes in the airway wall, airway lumenal size,
and wall thickness in vivo in moderate to severe asthmatics. Furthermore, these
studies will target specific products of airway inflammation and extracellular
matrix to establish their involvement in the process that leads to the chronic
changes that prevent airway distensibility and cause unresponsive asthma.
描述(改编自申请人摘要):哮喘是一种慢性疾病
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The effects of systemic lidocaine on airway tone and pulmonary function in asthmatic subjects.
全身利多卡因对哮喘受试者气道张力和肺功能的影响。
- DOI:10.1213/01.ane.0000260638.57139.87
- 发表时间:2007
- 期刊:
- 影响因子:5.7
- 作者:Chang,Herng-YuSucie;Togias,Alkis;Brown,RobertH
- 通讯作者:Brown,RobertH
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Robert H Brown其他文献
Amyotrophic Lateral Sclerosis: Fuel for the Corticofugal Feud
肌萎缩侧索硬化症:皮质不和的燃料
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:11.2
- 作者:
B. Wainger;Robert H Brown - 通讯作者:
Robert H Brown
Arterial delivery of myoblasts to skeletal muscle
成肌细胞经动脉输送至骨骼肌
- DOI:
10.1212/wnl.42.12.2258 - 发表时间:
1992 - 期刊:
- 影响因子:9.9
- 作者:
A. Neumeyer;D. Digregorio;Robert H Brown - 通讯作者:
Robert H Brown
Superoxide dismutase and familial amyotrophic lateral sclerosis: New insights into mechanisms and treatments
超氧化物歧化酶与家族性肌萎缩侧索硬化症:机制和治疗的新见解
- DOI:
10.1002/ana.410390202 - 发表时间:
1996 - 期刊:
- 影响因子:11.2
- 作者:
Robert H Brown - 通讯作者:
Robert H Brown
A Handoffs Software Led to Fewer Errors of Omission and Better Provider Satisfaction: A Randomized Control Trial
交接软件可以减少遗漏错误并提高提供商满意度:随机对照试验
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:2.2
- 作者:
M. Kashiouris;C. Stefanou;Deepankar Sharma;Cecilia Yshii;R. Vega;Sarah Hartigan;Charles R. Albrecht;Robert H Brown - 通讯作者:
Robert H Brown
Quantifying and Mitigating Motor Phenotypes Induced by Quantifying and Mitigating Motor Phenotypes Induced by Antisense Oligonucleotides in the Central Nervous System Antisense Oligonucleotides in the Central Nervous System
量化和减轻中枢神经系统中反义寡核苷酸诱导的运动表型 量化和减轻中枢神经系统中反义寡核苷酸诱导的运动表型
- DOI:
- 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
Michael P. Moazami;Julia M. Rembetsy;Feng Wang;P. M. Krishnamurthy;Alexandra Weiss;M. Marosfoi;Robert M. King;M. Motwani;H. Gray;Katherine A. Fitzgerald;Robert H Brown;Jonathan K. Watts - 通讯作者:
Jonathan K. Watts
Robert H Brown的其他文献
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{{ truncateString('Robert H Brown', 18)}}的其他基金
Micro Coherence Imaging Technology for Assessing Obstructive Lung Disease in vivo
用于评估体内阻塞性肺病的微相干成像技术
- 批准号:
8756282 - 财政年份:2014
- 资助金额:
$ 32.7万 - 项目类别:
Micro Coherence Imaging Technology for Assessing Obstructive Lung Disease in vivo
用于评估体内阻塞性肺病的微相干成像技术
- 批准号:
9276757 - 财政年份:2014
- 资助金额:
$ 32.7万 - 项目类别:
Mechanisms of Reduced Airway Distension in Severe Asthma
减少严重哮喘气道扩张的机制
- 批准号:
7392279 - 财政年份:2007
- 资助金额:
$ 32.7万 - 项目类别:
Mechanisms of Reduced Airway Distension in Severe Asthma
减少严重哮喘气道扩张的机制
- 批准号:
7312428 - 财政年份:2006
- 资助金额:
$ 32.7万 - 项目类别:
Mechanisms of Reduced Airway Distension in Severe Asthma
减少严重哮喘气道扩张的机制
- 批准号:
6967832 - 财政年份:2004
- 资助金额:
$ 32.7万 - 项目类别:
STRUCTURAL MECHANISMS OPERATING IN UNRESPONSIVE ASTHMA
无反应性哮喘的结构机制
- 批准号:
6129448 - 财政年份:2000
- 资助金额:
$ 32.7万 - 项目类别:
STRUCTURAL MECHANISMS OPERATING IN UNRESPONSIVE ASTHMA
无反应性哮喘的结构机制
- 批准号:
6390376 - 财政年份:2000
- 资助金额:
$ 32.7万 - 项目类别:
STRUCTURAL MECHANISMS OPERATING IN UNRESPONSIVE ASTHMA
无反应性哮喘的结构机制
- 批准号:
6537599 - 财政年份:2000
- 资助金额:
$ 32.7万 - 项目类别:
PULMONARY AIRWAY AND VASCULAR FUNCTION ASSESSED BY HRCT
HRCT 评估肺气道和血管功能
- 批准号:
2210581 - 财政年份:1992
- 资助金额:
$ 32.7万 - 项目类别:
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