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

NCT00974064 | Completed

• 1 other identifier: 0905010391
• Study Type: observational
• Target: 171
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

COPD; Lung disease; Chronic bronchitis; Emphysema; Smoking; Smoking cessation; Quit smoking; Healthy smoker; Smoker; Non-smoker

Outcome Measures

Primary Outcomes (1)

• Evaluate gene expression over time

  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.

  12/31/2013

Secondary Outcomes (1)

• Quitters who return to smoking and the effects on gene expression

  12/31/2012

Study Arms (5)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

New York Metropolitan area residents

You may qualify if:

• 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
• 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
• 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
• All study subjects will be enrolled in the "Airway" protocol #1204012331 "Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies"

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine

New York, New York, 10065-4870, United States

Location

Related Publications (1)

• Strulovici-Barel Y, Staudt MR, Krause A, Gordon C, Tilley AE, Harvey BG, Kaner RJ, Hollmann C, Mezey JG, Bitter H, Pillai SG, Hilton H, Wolff G, Stevenson CS, Visvanathan S, Fine JS, Crystal RG. Persistence of circulating endothelial microparticles in COPD despite smoking cessation. Thorax. 2016 Dec;71(12):1137-1144. doi: 10.1136/thoraxjnl-2015-208274. Epub 2016 Jul 26.

  PMID: 27462120 DERIVED

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.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Smoking; Smoking Cessation; Bronchitis, Chronic; Emphysema; Lung Diseases

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior; Health Behavior; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases

Study Officials

• Ronald G. Crystal, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2009
• First Posted: September 10, 2009
• Study Start: August 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 27, 2020

Record last verified: 2020-07

Locations

US (1)