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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

24 juli 2020 bijgewerkt door: 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.

Studie Overzicht

Toestand

Voltooid

Conditie

Gedetailleerde beschrijving

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.

Studietype

Observationeel

Inschrijving (Werkelijk)

171

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • New York
      • New York, New York, Verenigde Staten, 10065-4870
        • Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Allemaal

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

New York Metropolitan area residents

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Cohorten en interventies

Groep / Cohort
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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Evaluate gene expression over time
Tijdsspanne: 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.
12/31/2013

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Quitters who return to smoking and the effects on gene expression
Tijdsspanne: 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.
12/31/2012

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Weill Medical College of Cornell University

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 augustus 2009

Primaire voltooiing (Werkelijk)

1 juni 2013

Studie voltooiing (Werkelijk)

1 juni 2013

Studieregistratiedata

Eerst ingediend

9 september 2009

Eerst ingediend dat voldeed aan de QC-criteria

9 september 2009

Eerst geplaatst (Schatting)

10 september 2009

Updates van studierecords

Laatste update geplaatst (Werkelijk)

27 juli 2020

Laatste update ingediend die voldeed aan QC-criteria

24 juli 2020

Laatst geverifieerd

1 juli 2020

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 0905010391

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

ONBESLIST

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