Effects of Smoking on Bronchial Epithelium

University Medical Center Groningen60 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

Conditions

Asthma Copd

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

Epithelial integrity as measured with ECIS

Time frame: 2 years

Secondary Outcomes

Inflammatory cells and mediators

Time frame: 2 years

Production of inflammatory cytokines

Time frame: 2 years

Markers of epithelial integrity

Time frame: 2 years

Effects of Smoking on Bronchial Epithelium

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes