Respiratory and Cardiovascular Effects in COPD (KOLIN)
2016年4月5日 更新者:Dr Annelie F Behndig, MD PhD
Respiratory and Cardiovascular Effects in COPD - Report From a Bronchoscopy Investigation Based on the Obstructive Lung Disease In the Northern Sweden (OLIN) Studies
The purpose of this study is to find out if subjects with chronic obstructive pulmonary disease have signs of accelerated ageing in their airways.
研究概览
详细说明
The age-related impairment of innate immunity and antioxidant defenses likely impacts on development and disease progression of chronic obstructive pulmonary disease, COPD.
It has been suggested that aging-related declines in function are accelerated in COPD due to recurrent cycles of inflammation, tissue injury and repair, associated with long-term exposure to cigarette smoke or other airway irritants.
Here, the investigators aim to follow up on previous observations of impaired antioxidant responses in the lung of COPD patients, to establish the extent to which this reflects an accelerated aging phenotype, to characterize the molecular mechanisms resulting in this functional deficiency.
The proposed studies will employ well-characterized patients with COPD of varying severity and smoking habits, as well as carefully age and smoking history-matched controls.
Accelerated aging within the COPD lung will be assessed in endobronchial mucosal biopsies and airway macrophages by assessment of established senescence markers using immunohistochemical, biochemical and PCR-based methods.
These markers of tissue age will then be related to the functional activation of transcription factors, known to be induced by oxidative stress and related to cytoprotection such as Nrf2 and AP1.
The investigators will also examine whether COPD is associated with an enhanced secretion of inflammatory mediators from senescent cells, consistent with the accelerated aging paradigm and establish how this influences cell function.
Deficiencies in metal handling, antioxidant defenses and diminished airway innate immune defenses at the air-lung interface will be assessed.
The aim is to identify biomarkers for the risk of rapid lung function deterioration in COPD patients.
研究类型
介入性
注册 (实际的)
52
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
-
Sverige
-
Umeå、Sverige、瑞典、SE-90185
- Department of Public Health and Clinical Medicine, Division of medicine, Pulmonary medicine
-
-
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
45年 至 75年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Clinical diagnosis of COPD, GOLD stage 2-3.
- Smoking history of at least 10 packyears.
Exclusion Criteria:
- Severe ischemic heart disease.
- Other severe disease.
- Respiratory infection within four weeks.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:基础科学
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
其他:Healthy controls
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
|
Sampling of airways
|
其他:Smokers
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
|
Sampling of airways
|
其他:COPD rapid decline
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
|
Sampling of airways
|
其他:COPD slow decline
Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness
|
Sampling of airways
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Cellular senescence marker - Ki67
大体时间:Baseline
|
Endobronchial mucosal biopsies collected by bronchoscopy.
Immunohistochemistry for the cellular senescence markers Ki67 will be performed.
|
Baseline
|
Matrix metalloproteinase 12 (MMP12) and the inhibitor TIMP1
大体时间:Baseline
|
Airway lavages collected by bronchoscopy and serum will be analysed for MMP and TIMP using ELISAs.
|
Baseline
|
Levels of oxidized proteins, 4 HNE
大体时间:Baseline
|
The accumulation of oxidized proteins, 4-Hydroxynonenal, will be assessed in bronchial biopsies.
|
Baseline
|
Antioxidant-related transcription factor Nrf2
大体时间:Baseline
|
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor known to be induced by oxidative stress and related to cytoprotection.
|
Baseline
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Metals in airway lavages
大体时间:Baseline
|
Airway lavages collected by bronchoscopy will be analysed for metals using mass spectrometry
|
Baseline
|
Lymphocyte subsets in bronchoalveolar lavage
大体时间:Baseline
|
Airway lavages collected by bronchoscopy will be analysed for lymphocyte subsets using flow cytometry.
|
Baseline
|
Arterial stiffness
大体时间:Baseline
|
Non-invasive measurement of arterial stiffness
|
Baseline
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Eriksson Ström J, Pourazar J, Linder R, Blomberg A, Lindberg A, Bucht A, Behndig AF. Airway regulatory T cells are decreased in COPD with a rapid decline in lung function. Respir Res. 2020 Dec 14;21(1):330. doi: 10.1186/s12931-020-01593-9.
- Eriksson Strom J, Pourazar J, Linder R, Blomberg A, Lindberg A, Bucht A, Behndig AF. Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking. Respir Res. 2018 Dec 7;19(1):244. doi: 10.1186/s12931-018-0940-7.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2012年1月1日
初级完成 (实际的)
2014年12月1日
研究注册日期
首次提交
2016年2月24日
首先提交符合 QC 标准的
2016年4月5日
首次发布 (估计)
2016年4月6日
研究记录更新
最后更新发布 (估计)
2016年4月6日
上次提交的符合 QC 标准的更新
2016年4月5日
最后验证
2016年3月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.