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



Status:Completed
Conditions:Chronic Obstructive Pulmonary Disease, Smoking Cessation
Therapuetic Areas:Pulmonary / Respiratory Diseases
Healthy:No
Age Range:18 - Any
Updated:4/13/2015
Start Date:April 2011
End Date:March 2015
Contact:Charleen Hollmann, PhD
Email:chollmann@med.cornell.edu
Phone:646-962-2672

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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.

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.

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
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