Adiposity and Airway Inflammation in HIV-Associated Airway Disease

The proposed study involves the recruitment of participant population and the use of data
from the existing research study cohorts that have been recruited and have provided informed
consent for participation. Participants meet all inclusion/exclusion criteria will be
enrolled into the study. Participants in the existing research study cohorts have pulmonary
function testing, chest CT scans, and blood draws at each study visit which occurs every 18
months for 3 visits. Some of the study procedures may not be repeated if they were done as
part of other research projects.

1. Main study visit

The following research procedures may be performed over the course of one or more visits
to accommodate scheduling needs. The study visit will take place at the Montefiore
Clinical and Translational Research Center and the University of Pittsburgh Asthma
Institute in the University of Pittsburgh Medical Center - Montefiore Hospital and may
take up to 4 hours to complete.

- Informed consent

- Medical history review and demographics

- Review of inclusion/exclusion criteria

- Physical examination to include vital signs, weight and height, waist, hip, and
thigh circumferences.

- Urine pregnancy test for female of childbearing potential

- Asthma-focused and quality of life questionnaire

- Exhaled Nitric Oxide (eNO) measurement

- Spirometry

- Methacholine challenge testing - will not need to be repeated if the participant
had done this as part of another study in the past 6 months.

- Chest/Abdominal CT scans (If the participant has had the Chest CT scan done within
6 months as part of other research study, they will not be repeated for study
purposes. Only the Abdominal CT will be performed)

- Research blood sampling for biomarker analyses - some of this blood will also be
used for pre-bronchoscopy testing in the case that the participant qualifies and is
interested in undergoing part 2, the bronchoscopy visit.

- Adipose tissue biopsy (Fat Biopsy): performed on participants with a BMI≥25). This
will be repeated if done previously because testing to be done on the fat will be
different than what had been tested on the fat previously.

2. Optional sub-study

On a separate visit, only a subset of 60 selected participants will be asked to undergo the
following procedures to obtain additional lung biological samples. This visit is optional for
participants who are willing to participate in the bronchoscopy portion. The investigators
will try to recruit an equal number (n=15 per group) of obese asthmatics, obese
non-asthmatics, non-obese asthmatics, and non-obese non-asthmatics. The visit will take place
in the Montefiore Clinical Translational Research Center (MUH-CTRC). The bronchoscopy
procedure will take about 30-45 minutes, but the preparation and recovery time will usually
make the visit about 4-8 hours total.

Participants will be expected to fast for 8 hours prior to the bronchoscopy procedure and
refrain from drinking any liquids the day of the procedure. Participants may take their usual
medicines with sips of water.

• Clinical laboratory testing to include complete blood count/differential/platelet count,
prothrombin time/partial thromboplastin time, international Normalized Ratio, blood urea
nitrogen, and creatinine prior to bronchoscopy. If the patient refuses the first blood draw,
the sample is inadequate, or the labs were run more than 30 days prior to the bronchoscopy
visit, a second blood sample of up to 1 tablespoon may be drawn prior to the bronchoscopy
procedure to ensure the patient is healthy enough for the procedure.

If Methacholine challenge was done more than 30 days prior to the visit two date, pulmonary
function tests will be repeated.

- Oral Wash: participants will be asked to gargle with salt water for 1 minute and then
spit into a container to provide a sample of approximately 10mls (2 teaspoons) at this
study visit.

- Tongue Scraping: tongue blade or similar object will be used to scrape the participant's
tongue. This sample will be used to determine what bacteria are on the participant's
tongue. This procedure should only take minutes and is not painful.

- Participants will then rinse with 10cc's of Listerine. This is to assure that there are
no bacteria left behind in the participant's mouth prior to the bronchoscopy.

- Bronchoscopy with bronchoalveolar lavage (BAL), endobronchial brushing and biopsy

Under local anesthesia, participants will undergo bronchoscopy with BAL for microbiologic
specimens. A light intravenous anesthetic will be titrated to provide participant comfort if
necessary. Vitals signs will be monitored continuously before, during, and after the
procedure. This procedure consists of 3 stages.

1. Pulmonary Lavage: During pulmonary lavage, five 50 mL washes of sterile salt-water
solution will be injected through the bronchoscope. Fluid will be collected with gentle
suctioning for research studies.

2. Bronchial Brushing: A small brush will be introduced through the bronchoscope and gently
rubbed over a very small part of the surface of the lungs. Approximately 10 brushes will
be performed to collect epithelial cells.

3. Endobronchial Biopsy: While the bronchoscope is inserted, another small instrument will
be passed through the bronchoscope to take small samples (biopsies) of tissue from the
walls of the airways. Up to 5 samples may be taken during this procedure.

Following the bronchoscopy procedure, participants will be closely monitored in the
bronchoscopy recovery area or return to the CTRC. Rarely, the participant's asthma may worsen
during or after the procedure. Appropriate medical treatments or overnight observation will
be provided if needed. Participants will not be allowed to drive home after the bronchoscopy.
This is because the sedatives used during the procedure may decrease driving ability. The
investigators will ask for the contact name and number of the person that will pick up the
participant after the bronchoscopy

Inclusion Criteria:

1. 18 years of age or older

2. Subject who have been previously determined to be HIV positive through testing

Exclusion Criteria:

1. Pregnancy or breast-feeding

2. Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery
within 3 months, recent myocardial infarction, etc.)

3. Heart condition such as tachycardia, angina or arrhythmias

4. Acute respiratory infection: increasing respiratory symptoms or fever (temperature
>100.4°F [38°C]) within 4 weeks of study entry

5. Hospitalization within 4 weeks of study entry

6. Uncontrolled hypertension at screening visit (systolic > 160 mm Hg or diastolic > 100
mm Hg) from an average of two or more readings (participant may return for screening
after blood pressure is controlled)

7. Active cancer requiring systemic chemotherapy or radiation

8. Active infection of lungs, brain, or abdomen; or intravenous drug use or alcohol use
that will impair ability to complete study investigations in the opinion of the
investigator

9. History of prior lung resection