Implications and Stability of Clinical and Molecular Phenotypes of Severe Asthma

The longitudinal follow-up study is divided into a characterization and longitudinal phase.
During the characterization subjects will undergo a baseline evaluation that will include
will include answering questionnaires, lung function testing, and chest tomography.
Subsequently, to determine steroid responsiveness, all subjects will receive one
intramuscular dose of 40 mg in 1ml (1 mg/kg for children <18 years old, up to 40 mg maximum.
Participants at the University of Pittsburgh will undergo a bronchoscopy to provide airway
samples. The longitudinal phase will include a 36 month follow-up time with annual visits and
phone calls every 6 months. During it, participants will answer questionnaires and provide
sputum samples on two occasions, and will perform lung function testing.

The SARP III longitudinal follow up study (all centers) will determine the long term
stability and implications of clinical and molecular asthma phenotypes and identify potential
systemic biomarkers for these phenotypes

The University of Pittsburgh center will test the hypothesis that a) a mast cell signature is
present and longitudinally maintained in severe asthma; and b) That the persistent signature
determines short and long term outcomes through interactions with lung and inflammatory
cells.

Asthmatic Subjects

Inclusion Criteria:

- Previous asthma diagnosis

- FEV1 bronchodilator reversibility ≥12% or airway hyperresponsiveness reflected by a
methacholine PC20 ≤16 mg/mL (Historical methacholine data from previous NIH trial
[SARP I or II, AsthmaNet, ALA-ACRC, ACRN or CARE] will be allowed).

Exclusion Criteria:

- Exclusion criteria include any of the following:

- 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 (Note: if a subject has a smoking history, no smoking within the
past year),

- 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 18 and 65

- At least 3 of the 7 subjects per center should be aged 35 or older

Exclusion Criteria:

- History of chronic diseases that affect the lungs: Chronic airway disease (asthma,
cystic fibrosis, COPD, chronic bronchitis, bronchiectasis); Interstitial lung disease,
sarcoidosis, occupational lung disease; Obstructive sleep apnea; Vocal cord
dysfunction; Severe scoliosis or chest wall deformities.

- A history suggestive of allergic rhinitis (based on the best judgment of the physician
investigator).

- A history of eczema.

- Chronic sinusitis.

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

- Chronic systemic diseases requiring ongoing anti-inflammatory treatment.

- Current use of beta adrenergic blocking agent or a cholinesterase inhibitor (medicine
used to treat myasthenia gravis or Alzheimer's disease).

- 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).

- Respiratory tract infection within the past 4 weeks.

- Pregnancy.

- History of premature birth (<35 weeks).

- Any other criteria that place the subject at increased risk of complications from
study procedures, according to the judgment of the Principal Investigator and/or
attending physician(s) of record.