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- Essai clinique NCT00279136
Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma
Aperçu de l'étude
Statut
Les conditions
Description détaillée
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.
Type d'étude
Inscription
Contacts et emplacements
Coordonnées de l'étude
- Nom: Peter J. Sterk, MD, PhD
- Numéro de téléphone: +31 71 526 3578
- E-mail: p.j.sterk@lumc.nl
Sauvegarde des contacts de l'étude
- Nom: Annelies M. Slats, MD
- Numéro de téléphone: +31 71 526 3734
- E-mail: a.m.slatts@lumc.nl
Lieux d'étude
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Leiden, Pays-Bas, NL-2300 RC
- Recrutement
- Leiden University Medical Center
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Contact:
- Peter J. Sterk, MD, PhD
- Numéro de téléphone: +31 71 526 3578
- E-mail: p.j.sterk@lumc.nl
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Contact:
- Annelies M. Slats, MD
- Numéro de téléphone: +31 71 526 3734
- E-mail: a.m.slats@lumc.nl
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Chercheur principal:
- Peter J. Sterk, MD, PhD
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Peter J. Sterk, MD, PhD, Leiden University Medical Center
Publications et liens utiles
Liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement de l'étude
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- AF 3.2.02.34, DIACON
- Grant AF 3.2.02.34
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