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Sponsors and Collaborators: |
Leiden University Medical Center The Netherlands Asthma Foundation |
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Information provided by: | Leiden University Medical Center |
ClinicalTrials.gov Identifier: | NCT00279136 |
Asthma and COPD are characterized by airway narrowing. The most potent, physiological mechanism leading to bronchodilation is taking a deep inspiration. This protects healthy subjects against bronchoconstrictive stimuli, and reverses pre-existing bronchoconstriction. However, the deep breath-induced bronchoprotection and -bronchodilation is impaired in asthma. We questioned whether this is specific for asthma (in comparison to COPD), and whether this is associated with bronchial inflammation and -remodelling. The study is a two-groups comparison, of physiological and pathological disease markers, obtained by methacholine challenges, monitoring airways resistance, and by taking bronchial biopsies.
Condition |
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Asthma Chronic Obstructive Pulmonary Disease |
Study Type: | Observational |
Study Design: | Natural History, Cross-Sectional, Defined Population, Prospective Study |
Official Title: | Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma |
Estimated Enrollment: | 36 |
Study Start Date: | September 2004 |
Estimated Study Completion Date: | March 2006 |
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:
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.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contact: Peter J. Sterk, MD, PhD | +31 71 526 3578 | p.j.sterk@lumc.nl |
Contact: Annelies M. Slats, MD | +31 71 526 3734 | a.m.slatts@lumc.nl |
Netherlands | |
Leiden University Medical Center | Recruiting |
Leiden, Netherlands, NL-2300 RC | |
Contact: Peter J. Sterk, MD, PhD +31 71 526 3578 p.j.sterk@lumc.nl | |
Contact: Annelies M. Slats, MD +31 71 526 3734 a.m.slats@lumc.nl | |
Principal Investigator: Peter J. Sterk, MD, PhD | |
Principal Investigator: Peter J. Sterk, MD, PhD |
Study Chair: | Peter J. Sterk, MD, PhD | Leiden University Medical Center |
Study ID Numbers: | AF 3.2.02.34, DIACON, Grant AF 3.2.02.34 |
Study First Received: | January 17, 2006 |
Last Updated: | January 17, 2006 |
ClinicalTrials.gov Identifier: | NCT00279136 |
Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Bronchial hyperresponsiveness, lung function, airway inflammation, |
deep inspiration, bronchial biopsies airway smooth muscle |
Hypersensitivity Lung Diseases, Obstructive Respiratory Tract Diseases Lung Diseases Hypersensitivity, Immediate |
Asthma Bronchial Hyperreactivity Respiratory Hypersensitivity Inflammation Pulmonary Disease, Chronic Obstructive |
Immune System Diseases Bronchial Diseases |