Severe Asthma Research Program - University of Virginia

Through innovative metabolomics and redox biochemistry, methodologies that are a strength
and unique to our collaborative efforts, the investigators identified clinically relevant
phenotypes of asthma. The phenotypes are defined by biomarkers specific to underlying
biochemical mechanistic abnormalities, including eosinophil-mediated oxidation, depletion of
antioxidants and protective airway S-nitrosothiols, and airway acidification. Here,the
investigators propose to study a new component that is informative for longitudinal
assessment of severe asthma phenotypes: gender effects. The investigators reason that
identification of the metabolic mechanism(s) underlying onset of severe asthma in young
women during adolescence, and resolution of severe asthma in boys, will reveal fundamental
pathophysiology of severe asthma. Importantly, we aim to develop clinical testing procedures
to accurately assign metabolic asthma phenotypes; and to follow patients in each phenotype
to uncover clinical longitudinal outcomes. At the conclusion of the project, we anticipate
that we will have 1) developed clinically relevant tests to identify severe asthma
phenotypes; 2) determined the longitudinal outcome of the phenotypes; and 3) identified the
mechanisms underlying the preponderance of women in the severe asthma population. This
application will focus on the development or clinically relevant metabolic tests to identify
subphenotypes of adults and children with severe asthma and will lead to new targeted
innovative treatments.

Inclusion Criteria:

Physician diagnosis of asthma

• Age 6 years to 17 years old Evidence of historical reversibility, including either;

1. FEV1 bronchodilator reversibility greater than or equal to 12%, or

2. Airway hyperresponsivesness reflected by a methacholine PC20 less than or equal to 16
mg/ml.

Exclusion Criteria:

- Exclusion criteria include any of the following:

1. Pregnancy during the characterization phase*,

2. Current smoking,

3. Smoking history > 10 pack years if ≥30 years of age, or smoking history > 5 pack
years if <30 years of age (Note: if a subject has a smoking history, no smoking
within the past year),

4. Other chronic pulmonary disorders associated with asthma-like symptoms,
including (but not limited to) cystic fibrosis, chronic obstructive pulmonary
disease, chronic bronchitis, vocal cord dysfunction (that is the sole cause of
respiratory symptoms and at the PI's discretion), severe scoliosis or chest wall
deformities that affect lung function, or congenital disorders of the lungs or
airways,

5. History of premature birth before 35 weeks gestation,

6. Unwillingness to receive an intramuscular triamcinolone acetonide injection.

7. Evidence that the participant or family may be unreliable or poorly adherent to
their asthma treatment or study procedures,

8. Planning to relocate from the clinical center area before study completion,

9. Any other criteria that place the subject at unnecessary risk according to the
judgment of the Principal Investigator and/or attending physician(s) of record,
or

10. Currently participating in an investigational drug trial.