Effects of Smoking on Bronchial Epithelium

Completed

• Conditions: Asthma; Copd

• Registration Number: NCT00849433
• Lead Sponsor: University Medical Center 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-02-20
• Study First Submitted QC: 2009-02-20
• Study First Posted: 2009-02-23
• Study Start: 2009-04
• Primary Completion: 2012-04
• Study Completion: 2013-04
• Status Verified: 2015-01
• Last Update Submitted: 2015-01-15
• Last Update Posted: 2015-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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).

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Epithelial integrity as measured with ECIS	2 years

Secondary Outcome Measures

Name	Time	Method
Markers of epithelial integrity	2 years
Inflammatory cells and mediators	2 years
Production of inflammatory cytokines	2 years

Trial Locations

Locations (1)

University Medical Centre Groningen; 🇳🇱 Groningen, Netherlands