Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma
調査の概要
詳細な説明
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.
研究の種類
入学
連絡先と場所
研究連絡先
- 名前:Peter J. Sterk, MD, PhD
- 電話番号:+31 71 526 3578
- メール:p.j.sterk@lumc.nl
研究連絡先のバックアップ
- 名前:Annelies M. Slats, MD
- 電話番号:+31 71 526 3734
- メール:a.m.slatts@lumc.nl
研究場所
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Leiden、オランダ、NL-2300 RC
- 募集
- Leiden University Medical Center
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コンタクト:
- Peter J. Sterk, MD, PhD
- 電話番号:+31 71 526 3578
- メール:p.j.sterk@lumc.nl
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コンタクト:
- Annelies M. Slats, MD
- 電話番号:+31 71 526 3734
- メール:a.m.slats@lumc.nl
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主任研究者:
- Peter J. Sterk, MD, PhD
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
協力者と研究者
捜査官
- スタディチェア:Peter J. Sterk, MD, PhD、Leiden University Medical Center
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
研究の完了
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- AF 3.2.02.34, DIACON
- Grant AF 3.2.02.34
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