The Natural History of Gene Expression in the Lung Cells of Non-Smokers, Smokers and Ex-Smokers in Health and Disease
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Bronchitis, Bronchitis, Chronic Obstructive Pulmonary Disease, Smoking Cessation, Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/3/2018 |
| Start Date: | December 2009 |
| End Date: | March 2020 |
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.
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.
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.
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.
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
We found this trial at
1
site
New York, New York 10065
Click here to add this to my saved trials
