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.

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00849433

Enrollment

Registered

2009-02-23

Start date

2009-04-30

Completion date

2013-04-30

Last updated

2015-01-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma, Copd

Keywords

Inflammation, epithelial, integrity, ECIS

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame
Epithelial integrity as measured with ECIS	2 years

Secondary

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

Countries

Netherlands

Outcome results