Overview

This trial is active, not recruiting.

Conditions chronic obstructive pulmonary disease (copd), smoking, smoking cessation, chronic bronchitis, emphysema
Sponsor Weill Medical College of Cornell University
Start date December 2009
End date March 2017
Trial size 210 participants
Trial identifier NCT00974064, 0905010391

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model case control
Time perspective prospective
Arm
Healthy nonsmokers. Defined as non-smokers by self report and urine cotinine levels consistent with a nonsmoker (urine cotinine <5 ng/mL).
Healthy current smokers. Subjects categorized as healthy according to criteria under "Collection" (#1204012331) protocol.
Healthy smokers willing to quit. Defined by self-report and urine cotinine levels consistent with an active smoker (urine cotinine >50 ng/mL).
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)
Current smokers with COPD willing to stop smoking. Subjects have COPD as defined by the GOLD criteria

Primary Outcomes

Measure
Evaluate gene expression over time
time frame: 12/31/2013

Secondary Outcomes

Measure
Quitters who return to smoking and the effects on gene expression
time frame: 12/31/2012

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Group A: Healthy nonsmokers - Enrolled in the "Normal" protocol #0005004439 "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy" - Healthy according to the "Normal" protocol #0005004439 - 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 - smoked < 100 cigarettes per lifetime and whose urine nicotine <2 ng/mL and urine cotinine <5 ng/mL, at entry into the study Group B: Healthy current smokers Inclusion: - Enrolled in the "Normal" protocol #0005004439 - Healthy according to the "Normal" protocol #0005004439 - 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 urine cotinine >50 ng/mL Group C: Healthy smokers who elect to stop smoking Inclusion: - Enrolled in the "Normal" protocol #0005004439 - Healthy according to the "Normal" protocol #0005004439 - 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 urine cotinine >50 ng/mL - Willing to stop smoking Group D - Current smokers with COPD Inclusion: - Enrolled in the "Lung Disease" protocol #0005004440 "Evaluation of the Lungs of Individuals with Lung Disease with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing and Bronchial Wall Biopsy" - Meets the "Lung Disease" protocol criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure - 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 urine cotinine >50 ng/mL Group E - Current smokers with COPD who elect to stop smoking Inclusion: - Enrolled in the "Lung Disease" protocol #0005004440 - Meets the "Lung Disease" protocol criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure • 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 urine cotinine >50 ng/mL - Willing to stop smoking Exclusion Criteria: Groups A - E - Unable to provide proper informed consent - Drug and/or alcohol abuse within the past six months - Individuals with asthma and with recurrent or recent (within three months) and/or acute pulmonary infection - 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 - Major depression or other significant psychiatric disorder - HIV+ - Subjects that have unstable coronary artery disease as evidenced by unstable angina, >Class II 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 - Any 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

Additional Information

Official title The Natural History of Gene Expression in Lung Cells of Non-Smokers, Smokers, and Ex-Smokers in Health and Disease
Principal investigator Ronald G. Crystal, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Weill Medical College of Cornell University.