Phase I Assessment of Hypertonic Saline in Moderate to Severe Asthmatics

Participants: Non-smoking adults with well controlled moderate to severe asthma

Procedures (methods): After undergoing a general health screen, participants will undergo a
lung transmission scan to create an image of the lungs. Participants will then inhale
nebulized radiolabeled aerosol and sit in front of a gamma camera for 2 hours to measure
clearance of radiolabeled particles from the lungs (procedure called gamma scintigraphy),
which will be used to calculate baseline MCC. Participants will then inhale HS, with
spirometry performed before and at regular intervals after HS to assess for clinically
significant reductions in lung function. Vital signs and symptom questionnaires will be
administered as well. If they are deemed tolerant to HS (i.e. no clinically significant
deterioration in lung function, vital signs, or symptom questionnaire scores), participants
will move forward to the next study visit. At the next visit, participants will again inhale
nebulized HS and will undergo a gamma scintigraphy scan immediately after to measure the
acute effects of HS on MCC. At a separate visit, participants will inhale nebulized HS and
undergo gamma scintigraphy scan 4 hours later to measure prolonged effects of HS on MCC.

Inclusion Criteria:

- Age 18-60 of both genders-

- Moderate to severe asthma at baseline (determined by Step 3 therapy or greater or by
asthma impairment) and well-controlled asthma at the time of enrollment, as determined
by NHLBI Expert Panel Report 3 guidelines for diagnosis and treatment of asthma.

- Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy.

- FEV1 (forced expiratory volume 1 sec) of at least 70% of predicted for age, sex,
height, and race/ethnicity (without use of bronchodilating medications for 12 hours or
long acting beta agonists for 24 hours).

Exclusion Criteria:

Subjects who meet any of these criteria are not eligible for enrollment as study
participants:

1. Clinical Contraindications:

Any chronic medical condition considered by the PI as a contraindication to the study
including significant cardiovascular disease, diabetes, chronic renal disease, chronic
thyroid disease, history of chronic infections/immunodeficiency, or history of
tuberculosis Any acute infection requiring antibiotics within 4 weeks of study. Mental
illness or history of drug or alcohol abuse that, in the opinion of the investigator,
would interfere with the participant's ability to comply with study requirements.

Medications which may impact the results of the study treatment, or may interfere with
any other medications potentially used in the study (to include steroids, beta
antagonists, non-steroidal anti-inflammatory agents) Active smoking to include
e-cigarettes within 1 year of the study, or lifetime of > 10 pack-years of smoking
Allergy/sensitivity to study drugs, or their formulations. History of intubation for
asthma Unwillingness to use reliable contraception if sexually active (birth control
pills/patch, condoms).

Viral upper respiratory tract infection within 4 weeks of challenge. Radiation
exposure history in the past year that would cause the participant to exceed Federal
radiation safety guidelines.

2. Pregnant women and children (< 18 years as this is age of majority in NC) will also be
excluded since the risks associated with hypertonic saline inhalation to the fetus or
child and the risk of radiation are unknown and cannot be justified.

3. Use of the following medications:

1. Systemic corticosteroids; subjects with systemic corticosteroid-dependent asthma
will be excluded. All use of systemic steroids in the last year will be reviewed
by a study physician.

2. Use of daily theophylline within the past month

3. Use of any immunosuppressant/immunomodulatory therapy within the preceding 12
months

4. Use of beta blocking medications

5. Receipt of LAIV (Live Attenuated Influenza Vaccine), also known as FluMist®,
within the prior 30 days, or any vaccine within the prior 5 days

6. Multivitamins, Vitamin C or E or herbal medications in the 4 days prior to the
treatment visit

7. Non-steroidal anti-inflammatory drugs in the 4 days prior to the treatment visit

8. Subjects must be able to withhold morning doses of maintenance inhalers on the
treatment days, including long acting bronchodilators and inhaled
corticosteroids.

4. Allergy/sensitivity to study drugs or their formulations: Known IgE-(Immunoglobulin E)
mediated hypersensitivity to albuterol, diphenhydramine or corticosteroids.

5. Physical/laboratory indications:

1. Abnormalities on lung auscultation

2. Temperature > 37.8

3. Systolic BP >150 mm Hg or < 90 mm Hg or diastolic BP> 90 mm Hg or < 50

4. Oxygen saturation of < 93%

6. Inability or unwillingness of a participant to give written informed consent.