Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma
研究概览
详细说明
Rationale. Asthma is associated with variable airways obstruction and airways inflammation. It is generally assumed that inflammatory mechanisms are promoting airway narrowing, by stimulating airway smooth muscle and by geometrical changes of the airway wall. Healthy subjects are very effectively protected against stimuli of airway narrowing, by mechanisms that are apparently failing in asthma. The most potent inhibitor of airway narrowing in healthy subjects is taking a deep inspiration. This prevents and reverses bronchoconstriction (DI-induced bronchoprotection and -bronchodilation, respectively), which is less effective or absent in asthma. The DI-induced inhibition of airway narrowing in normal subjects is presumably due to relaxation of smooth muscle after mechanical stretch or to the release of relaxant mediators (such as endogenous NO). Such mechanisms might have become impaired in asthma, secondary to e.g. mechanical uncoupling of smooth muscle from the surrounding parenchyma (e.g. by congestion or edema), by altered structure and function of airway smooth muscle, and/or by reduced inhibitory mediator release.
It can be postulated that the impaired response to deep inspiration is a central pathophysiological feature of asthma at all ages. Therefore, we believe that it is imperative to address this, by identifying and restoring these inhibitory pathways in patients with asthma.
Hypotheses.
We hypothesize that DI-induced bronchoprotection and -broncho¬dilation:
- are associated with cellular and morphological features of airways inflammation,
- can be restored by deep insufflation rather than deep inspiration, and by pharmacological interventions aimed to reduce microvascular congestion or to increase endogenous nitric oxide synthesis..
Design and methods. To examine to what extent DI-responses differ between asthma and COPD in adulthood, and whether this is associated with features of airways inflammation and changes in smooth muscle function. 12 Adult patients with asthma and 12 with COPD will undergo single-dose methacholine challenge, with prohibition of DI's or 5 DI's prior to challenge in a cross-over design, measuring airways resistance. On a separate day bronchial biopsies will obtained with immunohistochemistry for inflammatory cell markers, vascularity, microvascular leakage, myosin light chain kinase, NO-synthases, and arginase.
研究类型
注册
联系人和位置
学习联系方式
- 姓名:Peter J. Sterk, MD, PhD
- 电话号码:+31 71 526 3578
- 邮箱:p.j.sterk@lumc.nl
研究联系人备份
- 姓名:Annelies M. Slats, MD
- 电话号码:+31 71 526 3734
- 邮箱:a.m.slatts@lumc.nl
学习地点
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Leiden、荷兰、NL-2300 RC
- 招聘中
- Leiden University Medical Center
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接触:
- Peter J. Sterk, MD, PhD
- 电话号码:+31 71 526 3578
- 邮箱:p.j.sterk@lumc.nl
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接触:
- Annelies M. Slats, MD
- 电话号码:+31 71 526 3734
- 邮箱:a.m.slats@lumc.nl
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首席研究员:
- Peter J. Sterk, MD, PhD
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Asthma according to GINA criteria (www.ginasthma.org)
- COPD according to GOLD criteria (www.goldcopd.org)
Exclusion Criteria:
- nonsmoking
- inhaled or oral steroid therapy
学习计划
研究是如何设计的?
设计细节
合作者和调查者
调查人员
- 学习椅:Peter J. Sterk, MD, PhD、Leiden University Medical Center
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
研究完成
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- AF 3.2.02.34, DIACON
- Grant AF 3.2.02.34
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