Regulation of the Release of Inflammatory Mediators From Blood Leukocytes
Regulation of the Release of Inflammatory Mediators From Blood Leukocytes: A Comparison of Healthy Subjects, Healthy Smokers and Patients With COPD.
研究概览
详细说明
The aim of this study is to investigate the mechanisms that regulate the survival of blood leukocytes as well as the synthesis and release of inflammatory mediators from cells from normal individuals and subjects with COPD. The hypothesis is that in COPD the life-span of leukocytes, such as the neutrophil, is enhanced and this may contribute to inflammation, a prominent characteristic of this disease, by secreting and releasing inflammatory mediators. We also suggest that differences may exist in the sensitivity of the various leukocytes to different therapies.
Leukocytes will be purified from the peripheral venous blood of patients with COPD as well as healthy individuals. We will then investigate the effects of novel and existing therapeutic agents on leukocyte survival and inflammatory mediator synthesis and release. We will also examine the regulation and release of enzymes known to damage lung tissue. Further studies will be carried out to elucidate the signal transduction pathways that lead to the activation, altered longevity and function of leukocytes. In other experiments ribonucleic acids or RNA may be extracted form leukocytes to investigate which genes are involved. The primary objective is to identify the mechanisms that enhance leukocyte longevity and inflammatory mediator and/or enzyme synthesis and release with a view to identifying novel targets for drug therapy.
研究类型
联系人和位置
学习地点
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London
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Chelsea、London、英国、SW3 6LY
- National Heart & Lung Institute, Imperial College
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Healthy non-smoking subjects: All normal volunteers will meet the following criteria:
- Age 21-70 years.
- No history of respiratory or allergic disease.
- Normal baseline spirometry as predicted for age, sex and height.
- Non-smokers.
- No history of upper respiratory tract infection in the preceding six weeks.
- Not taking regular medication
COPD subjects: COPD is diagnosed according to American Thoracic Society, European Respiratory Society and British Thoracic Society guidelines by the doctors in Professor Barnes' COPD clinic. All COPD volunteers will meet the following criteria:
- Age between 40-75 years.
- A smoking history of at least 20 pack years. ( 1 pack year = 20 cigarettes per day for 1 year)
- FEV1:FVC ratio of <0.7, post-bronchodilator FEV1 of <85% predicted, reversibility with inhaled b2-agonist of <15% of predicted FEV1: all three criteria are required.
- Current smokers or smokers who had ceased smoking for at least 6 months.
- No history of exacerbation, oral steroid or antibiotic use within the preceding 6 weeks.
- Normal serum a-1 antitrypsin level.
- No history of other respiratory or allergic disease.
- No evidence of atopy on skin prick testing to common aeroallergens (grass pollen, cat hair, house dust mite or Aspergillus fumigatus
- These tests will have already been performed as part of routine assessment in Professor Barnes' COPD clinic and we will not need to repeat them for this study.
Healthy Smokers: All healthy smoking volunteers in trials will meet the following criteria:
- Age 21-70 years.
- Smoking history of at least 10 pack years (1 pack year = 20 cigarettes per day for 1 year).
- No history of respiratory or allergic disease.
- Normal baseline spirometry as predicted for age, sex and height.
- No history of upper respiratory tract infection in the preceding six weeks.
- Not taking regular medication.
Exclusion Criteria:
Subjects will not included in this study if they meet any of the following exclusion criteria:
- Clinically significant findings in the medical history or on physical examination other than those of COPD in the COPD group.
- Pregnant women or mothers who are breastfeeding.
- Subjects who are unable to give informed consent.
学习计划
研究是如何设计的？
设计细节
合作者和调查者
合作者
调查人员
- 首席研究员：Peter J Barnes, DSc、National Heart & Lung Institute, Imperial College
研究记录日期
研究主要日期
学习开始 (预期的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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