Severe Asthma Research Program (SARP)- San Francisco Clinical Site

The mission of the SARP is to improve the understanding of severe asthma to develop better
treatments. The SARP will gain a better understanding of asthma and its endotypes, in
children and adults, by defining the disease at the molecular and cellular levels in the
context of the temporal phenotypic expression of the disease. To this end, the SARP
investigators will utilize both mechanistic and evoked phenotype approaches to: 1)
characterize developmental molecular, cellular and physiologic phenotypes in children and
adults with mild to severe asthma, and 2) to further elucidate the evolving pathobiology and
pathogenesis of severe asthma and its sub-phenotypes and 3) compare these features over time.

This approach involves a shared longitudinal protocol conducted across all participating
centers which includes common information on all SARP participants. Additionally, the SARP-SF
has identified mechanistic research questions to be included in the shared longitudinal
protocol. This will be explored through additional sample collections of sputum and fluids
and biopsied tissue collected by bronchoscopy. Together, these longitudinal and mechanistic
approaches will enable prediction of phenotype stability/fluctuation and pharmacologic
responses and identification of novel, disease-modifying targets for treatment.

Inclusion Criteria:

- FEV1 bronchodilator reversibility ≥12% or airway hyperresponsiveness reflected by a
methacholine PC20 ≤16 mg/mL

- An exception will be made for enrollees whose FEV1 is < 50% predicted (<70% in
children aged 6 to 17 years), precluding methacholine challenge testing. If
bronchodilator reversibility is <12% in these participants, a diagnosis of asthma
acceptable to the investigator is sufficient for inclusion in SARP.

Exclusion Criteria:

- Pregnancy during the characterization phase,

- Current smoking,

- Smoking history > 10 pack years if ≥30 years of age, or smoking history > 5 pack years
if <30 years of age,

- 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,

- History of premature birth before 35 weeks gestation,

- Unwillingness to receive an intramuscular triamcinolone acetonide injection

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

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

- 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

- Currently participating in an investigational drug trial.

Healthy Controls:

Inclusion criteria: Healthy subjects between the age of 18y and 65y. At least 3 of the 7
subjects per center should be aged 35y or older.

Exclusion criteria

- History of chronic diseases that affect the lungs.

- A history suggestive of allergic rhinitis, eczema or chronic sinusitis.

- An improvement in FEV1 of more than 12% following 4 puffs of albuterol.

- Smoking history > 10 pack years if ≥30 years of age, or smoking history > 5 pack years
if <30 years of age, or any smoking within the past year.

- Respiratory tract infection within the past 4 weeks.

- Pregnancy.

- History of premature birth (<35 weeks).