Acute and Chronic Inflammatory Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD: From Specific Disease Phenotyping Towards Novel Therapy (Study 2).
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Systemic inflammation assessed by measurement of expression of established and newly developed markers on innate immune cells; genomic and proteomic analysis of innate immune cells and measurement of pro- and anti-inflammatory cytokines in plasma/serum
研究概览
简要总结
COPD is ranked number 3 by the WHO list of important diseases worldwide and is the only disease with increasing mortality. The pathogenesis of cigarette smoke-induced COPD is obscure, therefore more insight is needed to design effective anti-inflammatory agents. Recently it has become clear that cigarette smoke-induced inflammation is not only present in the lungs but also in the blood, and that this systemic inflammation has important consequences for the clinical expression of COPD. The investigators hypothesize that healthy individuals who are susceptible to cigarette smoking demonstrate a higher and aberrant systemic inflammatory response to cigarette smoke. This susceptibility is caused by heterogeneous factors and is associated with various polymorphic genes that interact with each other and with the environment.
Objective:
- To study systemic inflammation in individuals who are or are not susceptible to develop COPD.
- To characterize the switch to chronicity of the systemic inflmmatory response in COPD
- To determine whether the type and severity of the systemic inflammation contributes to the clinical outcome of COPD
- To compare between subjects who are or are not susceptible to develop COPD in peripheral blood, the corticosteroid responsiveness in vitro, and to unravel underlying mechanisms.
- To study the role of candidate genes that may play a role in the development of fixed airway obstruction, and to identify clues for patient's responsiveness to specific drugs
- To develop new biological and clinical markers for the early diagnosis and monitoring of COPD
- To define possible mediators involved in the early induction of COPD in susceptible smokers, and to define new drug targets
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 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
- 是
入选标准
- •Age ≥18 and ≤75 years
- •Age, pack years, FEV1/FVC and FEV1% predicted must fit in one of the 9 groups of the study population
- •Physically and mentally able to undergo the total study protocol
- •Written informed consent
排除标准
- •Participation in another study
- •Alpha-1-antitrypsin deficiency
- •Selected grade 1-3 co-morbidity listed in the ACE-27
- •Active pulmonary infection like tuberculosis, pneumonia, flue, tracheobronchitis
- •Active extra-pulmonary infection like hepatitis A-C, cystitis, gastro-enteritis etc
- •Pulmonary diseases like sarcoidosis, pulmonary fibrosis, silicosis, hypersensitivity pneumonitis, asthma
- •Life threatening diseases like carcinoma, AIDS (including HIV+), acute leukaemia etc
- •Medication that may affect the results of the study: NSAID's, immunosuppressive agents like prednisolon, metotrexate, azathioprine
结局指标
主要结局
Systemic inflammation assessed by measurement of expression of established and newly developed markers on innate immune cells; genomic and proteomic analysis of innate immune cells and measurement of pro- and anti-inflammatory cytokines in plasma/serum
时间窗: 4 years
次要结局
- Extensive clinical characterisation of: a) young healthy individuals with low number of pack years who have a high and low familial risk to develop COPD; b) older individuals with higher number of pack years with either a normal lung function or COPD.(4 years)
- Important clinical endpoints include symptoms, lung function, Bode-index, CT-scanning of the lung.(4 years)
- Distribution of candidate genes (SNPs) for COPD between the different groups and relations with systemic inflammation.(4 years)