Modulation of Genes Responsible for Cilia Length by Exposure to Cigarette Smoke

Study Overview
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Brief Summary
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Cigarette smoking is the major risk factor for developing chronic obstructive pulmonary disease (COPD). Patients with COPD have difficulty clearing mucus and debris from their airways. Even smokers who have not developed COPD may have difficulty clearing the airways. This is partly because smoking impairs the function of cilia, tiny hairs lining the airways that sweep out mucus to keep the airways clean. The investigators have found that smoking reduces the length of cilia, which may contribute to the worsened cilia function in smoking and COPD. This is true even in smokers who show no signs of lung disease. The investigators believe that smoking affects levels of genes in lung cells, resulting in shorter cilia.

Detailed Description
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In this study, we will use bronchoscopy (inserting a scope into the lungs) to obtain lung cells by brushing cells from the airways and we will study genes that may be related to cilia length. Our goals are (1) to prove that exposure to cigarette smoke results in shorter cilia, (2) to learn which specific genes control cilia length, and (3) to learn how smoking affects the gene ODF2 and what effect this has on cilia. Understanding how smoking affects cilia may help us identify new ways to treat patients with COPD.

Official Title
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Modulation of Genes Responsible for Cilia Length by Exposure to Cigarette Smoke

Conditions
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COPD, Smoking

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be capable of providing informed consent Males and females, age 18 or older Nonsmoking, validated by venous carboxyhemoglobin and urine nicotine and cotinine within range for nonsmoker without smoke exposure, matched with smoker group by age, sex, ethnic/racial group 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, hepatitis B and C 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 Exclusion Criteria: Unable to meet the inclusion criteria Pregnancy Current active infection or acute illness of any kind 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) Evidence of malignancy within the past 5 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Healthy non-smokers | |
| Group 2<br>Healthy non-smokers | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence that exposure to cigarette smoke will result in shorter cilia length in human airway epithelial | Cilia length will be measured using three preparation techniques: air-dried cytospins, detached cilia on cytospins, and mounted hydrated aliquots of cells. | One Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Cigarette Smoke, Smoker, Nonsmoker, ODF2, Cilia