Lung Inflation and Airway Hyperresponsiveness

肺充气和气道高反应性

基本信息

  • 批准号:
    6805858
  • 负责人:
  • 金额:
    $ 47.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1998
  • 资助国家:
    美国
  • 起止时间:
    1998-12-15 至 2007-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Airways hyperresponsiveness (AHR) is a central feature of asthma, strongly related to the severity of the disease. However, its mechanisms are not understood. In the first period of this grant, we examined how lung inflation (deep inspiration) influences airways responsiveness. We identified that lung inflation has two distinct beneficial effects in healthy humans: it acts as a bronchoprotector and as a bronchodilator against bronchoconstrictive stimuli. We also found that the bronchoprotective effect of lung inflation is lost in individuals with AHR and is also absent against the bronchoconstriction induced by an allergic reaction. Preliminary findings indicate that the bronchodilatory effect is lost in subjects with COPD and in those with severe asthma. We now propose 3 specific aims: Specific aim 1 will test the hypothesis that nitric oxide (NO), which affects the airways smooth muscle by increasing the levels of cGMP, mediates the bronchoprotective effects of lung inflation and that the NO effect is impaired in AHR. This will be tested with the use of inhaled NO in healthy subjects and subjects with asthma with the intent to demonstrate that NO can mimic deep inspiration-induced bronchoprotection only in the former group. An analogous approach will be used by pre-treatment with sildenafil citrate, an approved inhibitor of PDE V, the enzyme responsible for cGMP degradation. Specific aim 2 will be devoted to the understanding of the mechanisms behind the absence of bronchoprotection against a respiratory allergic reaction. We will first examine whether an allergic reaction leads to the loss of bronchoprotection against other stimuli, such as methacholine. By using inhaled NO, we will examine whether the bronchoprotective action of this molecule is absent against an allergic reaction. With antagonists to products of the allergic reaction (primarily antileukotrienes and antihistamines), we will test whether we can restore the bronchoprotective effects of lung inflation against allergen. In specific aim 3 we will examine the reasons behind the loss of the bronchodilatory effect of lung inflation. Our hypothesis is that, in COPD, bronchodilation is lost as a result of impairment in lung elastic recoil, whereas in severe asthma, as a result of airway wall stiffness. To test this hypothesis, we will investigate these subject groups in comparison to healthy controls by simultaneously testing airways distensibility through high resolution computerized tomography imaging, recoil pressure at various lung volumes and bronchodilation by lung inflation.
描述(由申请人提供):气道高反应性(AHR)是哮喘的核心特征,与疾病的严重程度密切相关。但是,它的机制尚不清楚。在这笔赠款的第一阶段,我们研究了肺通胀(深度灵感)如何影响气道的反应。我们确定肺通货膨胀在健康人类中具有两个不同的有益作用:它是支气管保护剂,也是针对支气管收缩刺激的支气管扩张剂。我们还发现,AHR的个体中肺通胀的支气管保护作用损失,并且也没有因过敏反应引起的支气管收缩。初步发现表明,在患有COPD的受试者和严重哮喘患者中,支气管扩张作用丧失。现在,我们提出了3个特定目标:特定目标1将检验以下假设:一氧化氮(NO)通过增加CGMP的水平来影响气道平滑肌,介导肺通胀的支气管理效应,并且在AHR中无效。这将通过在健康受试者和患有哮喘的受试者中使用NO进行测试,目的是证明只能模仿以前组中的深层灵感引起的支气管造影。与CGMP降解的酶的PDE V的批准抑制剂Sildenafil柠檬酸盐(Sildenafil Citrate)预处理前进行了类似的方法。具体目标2将致力于理解缺乏呼吸过敏反应的支气管保护作用背后的机制。我们将首先检查过敏反应是否导致对其他刺激(例如甲基苯胺)的支气管施加丧失。通过使用吸入NO,我们将检查该分子的支气管保护作用是否不存在过敏反应。借助对过敏反应产物的拮抗剂(主要是抗胰甘油和抗组胺药),我们将测试是否可以恢复肺膨胀对过敏原的支气管理作用。在特定的目标3中,我们将研究肺通胀损失支气管扩张作用的原因。我们的假设是,在COPD中,由于肺弹性后坐力受损而导致支气管扩张降低,而在严重的哮喘中,由于气道壁刚度。为了检验这一假设,我们将通过高分辨率计算机断层扫描成像,各种肺体积的后坐压力以及通过肺通胀来调查这些主题组与健康对照组相比,通过高分辨率计算机断层扫描成像,后坐压力来扩大呼吸道。

项目成果

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N FRANKLIN ADKINSON其他文献

N FRANKLIN ADKINSON的其他文献

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{{ truncateString('N FRANKLIN ADKINSON', 18)}}的其他基金

CHILDHOOD ASTHMA MANAGEMENT PROGRAM - CONTINUATION STUDY - PHASE 2 (CAMP CS/2)
儿童哮喘管理计划 - 继续研究 - 第 2 阶段(CAMP CS/2)
  • 批准号:
    7375833
  • 财政年份:
    2005
  • 资助金额:
    $ 47.92万
  • 项目类别:
EFFECT OF SALICYLATE ON THE ALLERGIC PHENOTYPE
水杨酸盐对过敏表型的影响
  • 批准号:
    7375840
  • 财政年份:
    2005
  • 资助金额:
    $ 47.92万
  • 项目类别:
IRREVERSIBLE AIRWAY DISEASE IN ASTHMA: EXHALED BREATH
哮喘中的不可逆气道疾病:呼气
  • 批准号:
    7375832
  • 财政年份:
    2005
  • 资助金额:
    $ 47.92万
  • 项目类别:
LUNG CHANGES IN YOUNG ADULTS WITH MODERATE TO SEVERE ASTHMA-HRCT SCANS, METHACHS
患有中度至重度哮喘的年轻人的肺部变化-HRCT 扫描、方法
  • 批准号:
    7375837
  • 财政年份:
    2005
  • 资助金额:
    $ 47.92万
  • 项目类别:
CLINICAL TRIAL OF IMMUNOTHERAPY WITH A CANDIDATE EXTRACT OF NON-AMMONIATED LATEX
使用非氨化乳胶候选提取物进行免疫治疗的临床试验
  • 批准号:
    7375800
  • 财政年份:
    2005
  • 资助金额:
    $ 47.92万
  • 项目类别:
CLINICAL TRIAL OF IMMUNOTHERAPY WITH A CANDIDATE EXTRACT OF NON-AMMONIATED LATEX
使用非氨化乳胶候选提取物进行免疫治疗的临床试验
  • 批准号:
    7204431
  • 财政年份:
    2004
  • 资助金额:
    $ 47.92万
  • 项目类别:
IRREVERSIBLE AIRWAY DISEASE IN YOUNG ADULTS W/ MODERATE TO SEVERE ASTHMA
患有中度至重度哮喘的年轻人的不可逆气道疾病
  • 批准号:
    7204433
  • 财政年份:
    2004
  • 资助金额:
    $ 47.92万
  • 项目类别:
IRREVERSIBLE AIRWAY DISEASE IN ASTHMA: EXHALED BREATH
哮喘中的不可逆气道疾病:呼气
  • 批准号:
    7204467
  • 财政年份:
    2004
  • 资助金额:
    $ 47.92万
  • 项目类别:
CHILDHOOD ASTHMA MANAGEMENT PROGRAM - CONTINUATION STUDY
儿童哮喘管理计划 - 继续研究
  • 批准号:
    7204425
  • 财政年份:
    2004
  • 资助金额:
    $ 47.92万
  • 项目类别:
CHILDHOOD ASTHMA MANAGEMENT PROGRAM - CONTINUATION STUDY - PHASE 2 (CAMP CS/2)
儿童哮喘管理计划 - 继续研究 - 第 2 阶段(CAMP CS/2)
  • 批准号:
    7204468
  • 财政年份:
    2004
  • 资助金额:
    $ 47.92万
  • 项目类别:

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