Clinical trial NCT00849433: Effects of Smoking on Bronchial Epithelium
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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Copd
Keywords: Inflammation
epithelial
integrity
ECIS
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2009-02-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 30 patients with asthma; 30 patients with COPD

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Epithelial integrity as measured with ECIS
timeFrame: 2 years
Secondary outcomes:
measure: Inflammatory cells and mediators
timeFrame: 2 years
measure: Production of inflammatory cytokines
timeFrame: 2 years
measure: Markers of epithelial integrity
timeFrame: 2 years
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Maarten van den Berge, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: Dirkje S Postma, Professor
role: STUDY_DIRECTOR
References: