Effects of Smoking on Bronchial Epithelium

NCT00849433 | Completed

• 1 other identifier: METc2009008
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Copd

Keywords

Inflammation; epithelial; integrity; ECIS

Outcome Measures

Primary Outcomes (1)

• Epithelial integrity as measured with ECIS

  2 years

Secondary Outcomes (3)

• Inflammatory cells and mediators

  2 years

• Production of inflammatory cytokines

  2 years

• Markers of epithelial integrity

  2 years

Study Arms (2)

1

30 patients with asthma

2

30 patients with COPD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

30 patients with asthma; 30 patients with COPD

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Centre Groningen

Groningen, Provincie Groningen, 9713 GZ, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Bronchial biopsies Bronchial brushes Blood

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive; Inflammation

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Maarten van den Berge, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Dirkje S Postma, Professor

  University Medical Center Groningen

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: doctor

Study Record Dates

• First Submitted: February 20, 2009
• First Posted: February 23, 2009
• Study Start: April 1, 2009
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2013
• Last Updated: January 16, 2015

Record last verified: 2015-01

Locations

NL (1)