Smoking-induced EGF-dependent Reprogramming of Airway Basal Cell Function

NCT01974180 | Terminated

• 2 other identifiers: 1305013972Weill Cornell Medical College
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Early changes associated with the development of smoking-induced diseases, e.g., COPD and lung cancer (the two commonest causes of death in U.S.) are often characterized by abnormal airway epithelial differentiation. Airway basal cells (BC) are stem/progenitor cells necessary for generation of differentiated airway epithelium. Based on our preliminary observations that epidermal growth factor receptor, known to regulate airway epithelial differentiation, is enriched in BC and its ligand EGF is induced by smoking, we hypothesized that smoking-induced EGF alters the ability of BC to form normally differentiated airway epithelium. To test this, airway BC will be purified using a cell-culture method established in our laboratory and responses to EGF will be analyzed using genome-wide microarrays and an in vitro air-liquid interface model of airway epithelial differentiation.

Conditions

Smoking; COPD; Chronic Obstructive Pulmonary Disease

Keywords

Smoking; COPD; Chronic Obstructive Pulmonary Disease; Healthy Smoker; Non-smoker

Outcome Measures

Primary Outcomes (1)

• EGF induced gene expression changes related to smoking-associated phenotypes

  To determine whether stimulation of airway BC from healthy nonsmokers with EGF induces genes and pathways related to smoking-associated phenotypes, e.g. BC hyperplasia, squamous metaplasia, mucous metaplasia, abnormal cilia, decreased Clara cell number and compromised junctional integrity.

  One year

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:

• Must be capable of providing informed consent
• Males and females, age 18 or older
• Good overall health without history of chronic lung disease, including asthma, and without recurrent or recent (within 3 months) acute pulmonary disease
• Normal physical examination
• Normal routine laboratory evaluation, including general hematologic studies, general serologic/ immunologic studies, general biochemical analyses, and urine analysis
• Negative HIV serology
• Normal chest X-ray (PA and lateral)
• Normal electrocardiogram
• Females - not pregnant
• No history of allergies to medications to be used in the bronchoscopy procedure
• Not taking any medications relevant to lung disease or having an effect on the airway epithelium Willingness to participate in the study

You may not qualify if:

• Pregnancy
• Current active infection or acute illness of any kind
• Current alcohol or drug abuse
• Evidence of malignancy within the past 5 years

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, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Airway epithelial samples collected under IRB protocol #1204012331 will be used.

MeSH Terms

Conditions

Smoking; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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

Study Officials

• Renat Shaykhiev, MD, PHD

  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: October 25, 2013
• First Posted: November 1, 2013
• Study Start: December 3, 2013
• Primary Completion: April 16, 2015
• Study Completion: April 23, 2015
• Last Updated: December 26, 2017

Record last verified: 2017-12

Locations

US (1)