Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2005 by Leiden University Medical Center.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
The Netherlands Asthma Foundation
Information provided by:
Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT00279136
First received: January 17, 2006
Last updated: NA
Last verified: September 2005
History: No changes posted
  Purpose

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
Asthma
Chronic Obstructive Pulmonary Disease

Study Type: Observational
Study Design: Observational Model: Defined Population
Time Perspective: Cross-Sectional
Official Title: Towards Restoring the Physiological Inhibition of Airway Narrowing in Asthma

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Estimated Enrollment: 36
Study Start Date: September 2004
Estimated Study Completion Date: March 2006
Detailed Description:

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:

  1. are associated with cellular and morphological features of airways inflammation,
  2. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00279136

Contacts
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

Locations
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         
Sponsors and Collaborators
Leiden University Medical Center
The Netherlands Asthma Foundation
Investigators
Study Chair: Peter J. Sterk, MD, PhD Leiden University Medical Center
  More Information

Additional Information:
No publications provided by Leiden University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00279136     History of Changes
Other 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
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
Bronchial hyperresponsiveness,
lung function,
airway inflammation,
deep inspiration,
bronchial biopsies
airway smooth muscle

Additional relevant MeSH terms:
Asthma
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014