Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma
|ClinicalTrials.gov Identifier: NCT00279136|
Recruitment Status : Unknown
Verified September 2005 by Leiden University Medical Center.
Recruitment status was: Recruiting
First Posted : January 19, 2006
Last Update Posted : January 19, 2006
|Condition or disease|
|Asthma Chronic Obstructive Pulmonary Disease|
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.
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.
|Study Type :||Observational|
|Estimated Enrollment :||36 participants|
|Observational Model:||Defined Population|
|Observational Model:||Natural History|
|Official Title:||Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma|
|Study Start Date :||September 2004|
|Estimated Study Completion Date :||March 2006|
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00279136
|Contact: Peter J. Sterk, MD, PhD||+31 71 526 email@example.com|
|Contact: Annelies M. Slats, MD||+31 71 526 firstname.lastname@example.org|
|Leiden University Medical Center||Recruiting|
|Leiden, Netherlands, NL-2300 RC|
|Contact: Peter J. Sterk, MD, PhD +31 71 526 3578 email@example.com|
|Contact: Annelies M. Slats, MD +31 71 526 3734 firstname.lastname@example.org|
|Principal Investigator: Peter J. Sterk, MD, PhD|
|Study Chair:||Peter J. Sterk, MD, PhD||Leiden University Medical Center|