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.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Epithelial integrity as measured with ECIS
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- 未提供
结局指标
主要结局
Epithelial integrity as measured with ECIS
时间窗: 2 years
次要结局
- Markers of epithelial integrity(2 years)
- Inflammatory cells and mediators(2 years)
- Production of inflammatory cytokines(2 years)
研究者
Maarten van den Berge
doctor
University Medical Center Groningen