Effects of Smoking on Bronchial Epithelium

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.

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Copd

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Centre Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

30 patients with asthma; 30 patients with COPD

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; 30 patients with asthma
2; 30 patients with COPD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Epithelial integrity as measured with ECIS	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Inflammatory cells and mediators	2 years
Production of inflammatory cytokines	2 years
Markers of epithelial integrity	2 years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Maarten van den Berge, MD, PhD, University Medical Center Groningen; Study Director: Dirkje S Postma, Professor, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: February 20, 2009
• First Submitted That Met QC Criteria: February 20, 2009
• First Posted (Estimate): February 23, 2009

Study Record Updates

• Last Update Posted (Estimate): January 16, 2015
• Last Update Submitted That Met QC Criteria: January 15, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Inflammation; epithelial; integrity; ECIS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: METc2009008