Analyzing Lung Tissue in People With and Without Chronic Obstructive Pulmonary Disease Who Are Undergoing Lung Transplantation

COPD is a common lung disease and is the fourth most common cause of death in the United
States. Symptoms include coughing, excess mucus production, shortness of breath,and wheezing.
There is no cure for COPD, and the disease worsens over time. Treatment can include stopping
smoking, taking medications, receiving supplemental oxygen, and in severe cases, undergoing
lung transplantation. COPD is usually the result of many years of cigarette smoking, but it
remains unknown exactly how cigarette smoking causes this disease.

One reason that people with COPD experience shortness of breath and cough is because the lung
airways are partly damaged and obstructed. In healthy people, oxygen is breathed in and then
passes easily into the bloodstream through bunches of small air sacs that fill the lungs. In
people with COPD, these air sacs are damaged, making it difficult for oxygen to pass into the
bloodstream. However, even in people with severe COPD, the air sacs in some areas of the
lungs continue to work, even though neighboring air sacs are damaged. It is possible that an
overactive immune response may cause the air sac damage and that some people with COPD are
more prone than others to such immune system abnormalities. By examining the differences in
lung tissue in people with and without COPD who are undergoing a lung transplant, this study
will investigate why some people's immune systems cause lung damage and others do not and how
and why some air sacs are damaged while other nearby air sacs are not. Study researchers will
also examine whether genetic factors play a role in the development and severity of COPD.

This study will enroll people with COPD who are undergoing lung transplantation. Before the
lung transplantation surgery, participants will attend one study visit, which will include a
medical history review, height and weight measurements, and a blood collection. A portion of
blood will be stored for future genetic research. Participants will also complete
questionnaires to collect information on activities, health, and quality of life. Some
participants will undergo a 3-Helium magnetic resonance imaging (MRI) procedure, which is an
imaging technique that allows doctors to see the air spaces inside of the lungs. After the
lung transplantation surgery, study researchers will collect lung tissue from surgery. Study
researchers will contact participants at the end of the study to collect follow-up medical
information.

Inclusion Criteria:

- Age equal to or greater than 18 years

- Ability to read and write in English

- Able to participate in the informed consent process

- Listed at Barnes-Jewish Hospital for lung transplantation for COPD (with
alpha-1-antitrypsin deficiency [A1ATD] or non-1ATD)

- Global Initiative for Chronic Obstructive Lung Disease (GOLD) class IV COPD

- Acceptable chest computed tomography (CT) exam completed at Barnes-Jewish Hospital in
the 3 years before study entry

Exclusion Criteria:

- Pregnant

- Prisoner

- Vulnerable populations

- Coexisting active chronic inflammatory or collagen vascular disease, immunodeficiency
of any kind, non-cutaneous malignancy (melanoma is an exclusion), or previous organ
transplant

- Coexisting (other than COPD / emphysema / chronic bronchitis)significant pulmonary
parenchymal disorder (e.g., pulmonary fibrosis)

Exclusion Criteria for 3-Helium MRI Procedure:

- Inability to perform 10 to 15 second breath hold for 3-Helium MRI scan.

- Contraindications to MRI (including pacemaker, metal implants, other devices affected
by the magnet).

- Contraindications to 3-Helium MRI (including significant anemia [hemoglobin less than
or equal to 12 g/dL, with the last testing within 1 month of the MRI scan] or marked
oxyhemoglobin desaturation at rest when breathing room air [requiring more than 4
liters per minute of supplemental oxygen to keep saturation of oxygen (SaO2) at least
90%]).However, patients deemed to be low risk kfor complications of cerebrovascular
disease, cardiovascular disease, heart dysrhythmias, and seizures through the thorough
lung transplant evaluation will be eligible for testing. Since most of the patients
with these contraindications to 3-Helium MRI will be ineligible for lung
transplantation, we expect few patients to have such contraindications to testing.