Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics

This is a cross sectional pilot study comparing specific metabolic pathways in bronchial
airway epithelial cells and the nasal epithelium across the following patient groups:

1. Obese (Body Mass Index (BMI) ≥ 30) asthmatics without metabolic syndrome,

2. Obese asthmatics with metabolic syndrome,

3. Obese non-asthmatics, and

4. Non - obese (lean > 18 <= 25, Overweight (OW) > 25 - <30) asthmatics.

Participants in these groups will be matched by gender, age and asthma severity. To be
enrolled, participants must be non-current smokers and be controlled. After meeting screening
criteria, participants will undergo further evaluation to determine whether or not inclusion
and exclusion criteria are met. Participants will undergo a baseline evaluation, lung
function testing and a subsequent bronchoscopy and nasal epithelial brush sampling in those
that meet study enrollment.

Participants without a bronchodilator withhold will be scheduled to undergo a methacholine
test. Those that qualify will undergo a bronchoscopy to obtain bronchoalveolar lavage and
airway epithelial cells and nasal epithelial brush sampling for gene expression studies.
After the procedure is done and post bronchoscopy safety standards are met, participants will
be discharged from the inpatient Clinical Translational Research Center (CTRC) recovery area.
The research coordinator will call the participant on the night of the procedure and on the
next day to document post-procedure clinical stability.

Inclusion Criteria:

For ALL Groups

1. Adequate completion of informed consent process with written documentation

2. Male and female patients, ≥ 18 - 65 years old

3. Smoking history <10 pack years and no smoking in the last year

**Subjects can be included in the study if they are on blood pressure treatment and
are on a diet control/exercise only treatment of diabetes.

4. Specific to Asthma Groups

i. From all racial/ethnic backgrounds with a diagnosis of asthma based on physician
diagnosis for >6 months

1. Specific to Metabolic Syndrome Group. Metabolic syndrome diagnosis based on having at
least any three of: a. Triglycerides ≥ 150 mg/dl; b. High-density lipoproteins (HDL)
cholesterol ≤ 50 mg/dl for women and ≤ 40 mg/dl for men; c Fasting blood glucose ≥ 100
mg/dl; d. Waist circumference > 40 inches males and > 35 inches females); e.
Previously diagnosed hypertension or on antihypertensive medication; f. Blood pressure
greater than 130/85 on two consecutive measurements.

2. Specific to Non-Metabolic Syndrome Group a. Baseline pre-bronchodilator forced
expiratory volume (FEV1) of 50% or greater of predicted with a 12% or greater
bronchodilator (BD) response to 4 puffs of albuterol or PC20 methacholine (16 mg) if
no BD response; b. BMI ≥ 30

Metabolic syndrome diagnosis based on having at least any three of:

i. Triglycerides ≥ 150 mg/dl; ii. HDL cholesterol ≤ 50 mg/dl for women and ≤ 40 mg/dl
for men; iii. Fasting blood glucose ≥ 100 mg/dl; iv. Waist circumference > 40 inches
males and > 35 inches females); v. Previously diagnosed hypertension or on
antihypertensive medication; vi. Blood pressure greater than 130/85 on two consecutive
measurements.

3. Specific to Non-Obese Group a. Body Mass Index (BMI) < 30

b. Specific to Non-Asthma Group i. No history of asthma or any other airway diseases;
ii. Pulmonary function test within normal limits; iii. BMI ≥ 30.

Exclusion Criteria (all groups):

1. Significant or uncontrolled concomitant medical illness (PI discretion) including, but
not limited to heart disease, cancer, diabetes (HbAc1 > 6.5), renal disease
(creatinine > 2.0) at Visit 0, neurological (brain damage) or psychiatric disorder
(diagnosed by a mental health professional of behavioral or mental pattern that may
cause suffering or a poor ability to function in life);

2. Chronic renal failure (creatinine > 2.0) at screening (associated with higher
asymmetric dimethylarginine (ADMA) levels);

3. Current statins use (statins lower ADMA levels);

4. On diabetic medications;

5. Positive pregnancy test;

6. Positive urine cotinine and/or urine tetrahydrocannabinol (THC) test;

7. Current or recent (within 30 days) investigational treatment or participation in
another interventional research study (including non-pharmacologic interventions);

8. Unable or unlikely to complete study assessments or the study intervention (i.e.
bronchoscopy) poses undue risk to patient in the opinion of the investigator.

a. Specific to Asthma Groups i. Respiratory tract infection within the last 4 weeks;
ii. Oral or systemic corticosteroids (CS) burst within the last 4 weeks; iii.
Asthma-related hospitalization within the last 2 months; iv. Asthma-related ER visit
within the previous 4 weeks.