The Natural History of Gene Expression in the Lung Cells of Non-Smokers, Smokers and Ex-Smokers in Health and Disease
2020年7月24日 更新者：Weill Medical College of Cornell University
The Natural History of Gene Expression in Lung Cells of Non-Smokers, Smokers, and Ex-Smokers in Health and Disease
Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD, commonly known as chronic bronchitis and emphysema).
Despite this clear link, only 15-20% of smokers develop COPD suggesting that genetic factors affect the lung's susceptibility to the stress of cigarette smoke.
The cells lining the airways (epithelium) and cells that help defend the lung (alveolar macrophages) of smokers develop gene expression changes that are different from that of nonsmokers.
In the investigators' previous studies they have demonstrated that there are greater than 200 genes that are responsive to cigarette smoke in these cells.
But the investigators do not know whether the gene expression is static or changes as a function of time.
Genes that show significant changes over time may be relevant to the progression of the disease.
Even though quitting smoking reduces the rate at which the lungs decline, many-smokers still go on to develop COPD.
This study will provide insights into the natural history of smoking-related gene expression of the lung cells in health and disease.
研究概览
地位
完全的
条件
详细说明
Cigarette smoke is responsible for the majority of lung cancers and is the major cause of COPD, the fourth leading cause of death in the United States.
Despite the well established causal role of cigarette smoking in lung cancer and COPD, only 10-20% of smokers actually develop these diseases.
This suggests that there are genetic predisposing factors that place some individuals at greater risk.
Our prior work shows that healthy smokers (cigarette smokers with normal history, physical exam, lung function tests and chest x-rays) and smokers with COPD have marked up and down regulation of greater than 200 genes in the small airway epithelium and alveolar macrophages.
There is however, a varied response to smoking among individuals, with some individuals abnormally expressing far fewer genes.
The focus of this study is to evaluate the hypothesis that the response of the lung cells to the stress of smoking is unique to each individual but is consistent over time.
Furthermore, individuals that stop smoking will each have a unique response, but is constant over time for each individual.
By defining the patterns of biologic response over time among smoking, ex-smoking and nonsmoking subjects, we will be able to identify common biologic pathways as potential targets for intervention.
研究类型
观察性的
注册 (实际的)
171
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
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New York
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New York、New York、美国、10065-4870
- Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine
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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
18年 及以上 (成人、年长者)
接受健康志愿者
是的
有资格学习的性别
全部
取样方法
非概率样本
研究人群
New York Metropolitan area residents
描述
Inclusion Criteria:
Group A: Healthy nonsmokers
- All study individuals should be enrolled in the "Airway" protocol #1204012331 "Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies"
- Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Never smokers is defined as someone who has smoked < 100 cigarettes per lifetime and whose urine nicotine <2 ng/mL and/or urine cotinine <5 ng/mL, at entry into the study
Group B: Healthy current smokers Inclusion:
- All study individuals should be enrolled in the "Airway" protocol
- Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Active smoker as evidenced by self-report and urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL
Group C: Healthy smokers who elect to stop smoking Inclusion:
- All study individuals should be enrolled in the "Airway" protocol
- Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Current smoker as evidenced by self-report and urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL
- Be a current smoker willing to stop smoking
Group D - Current smokers with COPD Inclusion:
- All study subjects will be enrolled in the "Airway" protocol #1204012331 "Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies"
- All study subjects should meet the lung disease criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure
- All study subjects should be able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Active smokers as evidenced by urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL
Group E - Current smokers with COPD who elect to stop smoking Inclusion:
- All study subjects will be enrolled in the "Airway" protocol #1204012331 "Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies"
- All study subjects should meet the lung disease criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure
- All study subjects should be able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Active smokers as evidenced by urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL
- Be a current smoker willing to stop smoking
Exclusion Criteria:
Groups A - E
- Individuals unable to provide proper informed consent
- Habitual use of drugs and/or alcohol within the past six months (Acceptable: Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria)
- Individuals with asthma and with recurrent or recent (within three months) and/or acute pulmonary infection
- Individuals with allergy to lidocaine
- Significant kidney disease or subjects on dialysis
- Females who are pregnant or lactating or intending to become pregnant in the next 12 months
- Subjects who are HIV positive
- Subjects that have unstable coronary artery disease as evidenced by unstable angina, >Class II New York Heart Association (NYHA) cardiac status, history of congestive heart failure or MI within the last 12 months
- Subjects who are contraindicated for undergoing bronchoscopy
- Subjects having any medical condition that in the opinion of the investigator would preclude the subject from entering the study
Groups D and E
- Subjects may not have evidence of respiratory failure such as SpO2 <90% or PaO2 <60 mmHg
Groups C and E
- Current major depression or other significant psychiatric disorder
- Subjects currently taking anti-depressant medication
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
队列和干预
团体/队列 |
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A-Healthy Non smokers
Healthy nonsmokers.
Defined as non-smokers by self report and urine cotinine levels consistent with a nonsmoker (urine cotinine <5 ng/mL).
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B-Healthy smoker
Healthy current smokers.
Subjects categorized as healthy according to criteria under "Collection" (#1204012331) protocol.
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C-Healthy smoker to quit
Healthy smokers willing to quit.
Defined by self-report and urine cotinine levels consistent with an active smoker (urine cotinine >50 ng/mL).
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D-Current smoker w. COPD
Current smokers with COPD.
COPD as defined by the GOLD criteria and currently smoking as defined by self-report and urine cotinine levels consistent with an active smoker (urine cotinine >50 ng/mL)
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E-Current COPD smoker to quit
Current smokers with COPD willing to stop smoking.
Subjects have COPD as defined by the GOLD criteria
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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 |
|---|---|---|
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Evaluate gene expression over time
大体时间：12/31/2013
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To prospectively assess changes in lung cell gene expression over time in healthy nonsmokers, healthy smokers and smokers with COPD.
To examine what smoking-induced gene expression changes occur in the lung cells of healthy smokers and COPD smokers over time in response to cessation of smoking.
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12/31/2013
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Quitters who return to smoking and the effects on gene expression
大体时间：12/31/2012
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In individuals who quit but start smoking again despite the standard smoking cessation therapy, what are the effects on gene expression of returning to smoking.
To assess whether baseline gene expression determines what genes rapidly change to a more "normal" expression pattern with smoking cessation.
Does having established COPD determine the relative reversibility of the gene expression pattern with smoking cessation compared to healthy smokers.
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12/31/2012
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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
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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 (实际的)
2009年8月1日
初级完成 (实际的)
2013年6月1日
研究完成 (实际的)
2013年6月1日
研究注册日期
首次提交
2009年9月9日
首先提交符合 QC 标准的
2009年9月9日
首次发布 (估计)
2009年9月10日
研究记录更新
最后更新发布 (实际的)
2020年7月27日
上次提交的符合 QC 标准的更新
2020年7月24日
最后验证
2020年7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.