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The Natural History of Gene Expression in the Lung Cells of Non-Smokers, Smokers and Ex-Smokers in Health and Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00974064
First received: September 9, 2009
Last updated: May 23, 2017
Last verified: May 2017
  Purpose
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.

Condition
Chronic Obstructive Pulmonary Disease (COPD) Smoking Smoking Cessation Chronic Bronchitis Emphysema

Study Type: Observational
Study Design: Observational Model: Case-Control
Time Perspective: Prospective
Official Title: The Natural History of Gene Expression in Lung Cells of Non-Smokers, Smokers, and Ex-Smokers in Health and Disease

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Evaluate gene expression over time [ Time Frame: 12/31/2013 ]
    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.


Secondary Outcome Measures:
  • Quitters who return to smoking and the effects on gene expression [ Time Frame: 12/31/2012 ]
    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.


Biospecimen Retention:   Samples With DNA
Subjects will not have more than 550 mL of blood drawn over a period of 8 weeks. Airway epithelium from airway brushing samples and alveolar macrophages from bronchoalveolar lavage is processed to yield high quality RNA. Complimentary DNA (cDNA) is transcribed from the RNA in vitro and the product is hybridized onto gene microarray chips.

Estimated Enrollment: 210
Study Start Date: December 2009
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
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).
B-Healthy smoker
Healthy current smokers. Subjects categorized as healthy according to criteria under "Collection" (#1204012331) protocol.
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).
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)
E-Current COPD smoker to quit
Current smokers with COPD willing to stop smoking. Subjects have COPD as defined by the GOLD criteria

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
New York Metropolitan area residents
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00974064

Locations
United States, New York
Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine
New York, New York, United States, 10065-4870
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: Ronald G. Crystal, M.D. Weill Medical College of Cornell University
  More Information

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00974064     History of Changes
Other Study ID Numbers: 0905010391
Study First Received: September 9, 2009
Last Updated: May 23, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Weill Medical College of Cornell University:
COPD
Lung disease
Chronic bronchitis
Emphysema
Smoking
Smoking cessation
Quit smoking
Healthy smoker
Smoker
Non-smoker

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Emphysema
Pulmonary Emphysema
Bronchitis
Bronchitis, Chronic
Respiratory Tract Diseases
Pathologic Processes
Bronchial Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on August 17, 2017