Effects of Smoking on Bronchial Epithelium

Asthma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00849433
• Other study ID #: METc2009008
• Status: Completed
• Phase: N/A
• First received: February 20, 2009
• Last updated: January 15, 2015
• Start date: April 2009
• Est. completion date: April 2013

Study information

• Verified date: January 2015
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: Dutch Health Care Inspectorate
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2013
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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).

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Asthma
• Copd

Locations

Country	Name	City	State
Netherlands	University Medical Centre Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epithelial integrity as measured with ECIS		2 years	Yes
Secondary	Inflammatory cells and mediators		2 years	Yes
Secondary	Production of inflammatory cytokines		2 years	Yes
Secondary	Markers of epithelial integrity		2 years	Yes