Effects of Smoking on Bronchial Epithelium

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00849433
Recruitment Status : Completed
First Posted : February 23, 2009
Last Update Posted : January 16, 2015
Information provided by (Responsible Party):
Maarten van den Berge, University Medical Centre Groningen

Brief Summary:
Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases affecting millions of people worldwide. Inhaled corticosteroids (ICS) are by far the most effective treatment with a broad anti-inflammatory spectrum. Nevertheless, most COPD patients and a proportion of severe asthma patients are corticosteroid-resistant (CR) and to fail to respond to ICS even when higher doses are given. These corticosteroid-resistant patients suffer from persistent symptoms and repeated asthma exacerbations. It has been suggested that smoking and oxidative stress may induce corticosteroid-resistance. The reactive oxygen species (ROS) responsible for oxidative stress can be generated exogenously (air pollutants, cigarette smoke) and endogenously by metabolic reactions. After inhaling air pollutants or cigarette smoke, the bronchial epithelium is exposed. Preliminary data from our own lab suggest that smoking and oxidative stress may decrease epithelial cell-cell contact formation. This results not only in a decreased barrier function, but also in an increased production of pro-inflammatory mediators.

Condition or disease
Asthma Copd

Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effects of Smoking on Airway Remodeling and Phenotypic Changes of the Airway Epithelium in Asthma and COPD: Strategies to Restore the Epithelial Barrier, Repair and Steroid Sensitivity.
Study Start Date : April 2009
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Smoking
U.S. FDA Resources

30 patients with asthma
30 patients with COPD

Primary Outcome Measures :
  1. Epithelial integrity as measured with ECIS [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Inflammatory cells and mediators [ Time Frame: 2 years ]
  2. Production of inflammatory cytokines [ Time Frame: 2 years ]
  3. Markers of epithelial integrity [ Time Frame: 2 years ]

Biospecimen Retention:   Samples With DNA
Bronchial biopsies Bronchial brushes Blood

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
30 patients with asthma; 30 patients with COPD

Inclusion Criteria:

Inclusion criteria for patients with allergic asthma:

  • Age between 18 and 65 years.
  • < 10 packyears, no smoking in the last year.
  • The presence of allergy defined as at least one positive wheal/flare reaction (2 mm relative to control) to a skin prick test with sixteen common aero-allergens).
  • FEV1 > 80% predicted.
  • PC20 methacholine or PC20 histamine < 8 mg/ml.

Inclusion criteria for patients with COPD:

  • Age between 45-75 years.
  • ≥ 10 packyears.
  • FEV1 between 30% and 80% of predicted.

Exclusion criteria:

  • Any disease that, as judged by the Investigator, could have affected the outcome of this study.
  • A respiratory tract infection within 4 weeks of the start of the study.
  • A history of life-threatening asthma, defined as exacerbation of asthma or COPD that required intubation or was associated with hypercapnea.
  • History of myocardial infarction or documented myocardial ischemia.
  • Pregnancy, or the possibility of being pregnant (a pregnancy test will be performed in women of childbearing potential who do not use adequate anticonception as judged by the investigator).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00849433

University Medical Centre Groningen
Groningen, Netherlands, 9713 GZ
Sponsors and Collaborators
University Medical Center Groningen
Principal Investigator: Maarten van den Berge, MD, PhD University Medical Center Groningen
Study Director: Dirkje S Postma, Professor University Medical Center Groningen

Responsible Party: Maarten van den Berge, doctor, University Medical Centre Groningen Identifier: NCT00849433     History of Changes
Other Study ID Numbers: METc2009008
First Posted: February 23, 2009    Key Record Dates
Last Update Posted: January 16, 2015
Last Verified: January 2015

Keywords provided by Maarten van den Berge, University Medical Centre Groningen:

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases