Step-up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations

The study design is a double-blind, parallel-group trial, including a total of 250
participants, ages 5-11 years, with a diagnosis of asthma and a history of at least 1 asthma
exacerbation treated with oral corticosteroids in the prior year. All participants will be
treated for 48 weeks with open-label fluticasone 44 mcg 2 puffs twice daily. During the
48-week treatment period, participants will receive randomized blinded therapy for 7 days
each time they enter the "yellow zone" (at the onset of symptoms previously associated with
upper respiratory illnesses and subsequent asthma exacerbations). Yellow zone therapy will be
fluticasone 44 or 220 mcg 2 puffs twice daily.

Inclusion Criteria:

- Physician-diagnosed asthma

- At least 1 exacerbation treated with systemic (oral or injectable) corticosteroids in
the past 12 months

- Able to perform reproducible spirometry

- Current treatment with step 2 controller therapy [low-dose ICS, leukotriene receptor
antagonist (LTRA)] OR current treatment with step 3 controller therapy [low-dose ICS +
long-acting beta agonist (LABA), low-dose ICS + LTRA, or medium dose ICS] with a
childhood Asthma Control Test (c-ACT) score of >19, no more than 2 prednisone treated
exacerbations in the past 6 months, prebronchodilator Forced Expiratory Volume at 1
second (FEV1) ≥ 80% predicted and willing to step down therapy OR controller naïve and
qualifying for step 2 controller therapy [asthma symptoms or short acting beta agonist
(SABA) use > 2 days per week or night-time awakenings due to asthma > 2 nights per
month]

- Prebronchodilator FEV1 ≥ 60% predicted

- Ability and willingness to provide informed assent

- For females of childbearing potential: not pregnant, non-lactating, and agree to
practice an adequate birth control method.

- History of clinical varicella or varicella vaccine

Exclusion Criteria:

- Systemic (oral or injectable) corticosteroids within previous 2-week period

- Current or recent (previous 2-weeks) use of medications known to significantly
interact with corticosteroid disposition, including but not limited to carbamazepine,
erythromycin, phenobarbital, phenytoin, rifampin, and ketoconazole

- Presence of chronic or active lung disease other than asthma

- Significant medical illness other than asthma, including thyroid disease, diabetes
mellitus, Cushing's disease, Addison's disease, hepatic disease, or concurrent medical
problems that could require oral corticosteroids during the study

- A history of cataracts, glaucoma, or any other medical disorder associated with an
adverse effect to corticosteroids

- History of a life-threatening asthma exacerbation requiring intubation, mechanical
ventilation, or resulting in a hypoxic seizure

- More than 5 prednisone treated exacerbations in the past 12 months

- More than 1 hospitalizations lasting >24 hours for asthma in the past 12 months

- History of adverse reactions to ICS preparations or any of their ingredients

- Receiving hyposensitization therapy other than an established maintenance regimen (On
maintenance regimen for ≥ 3 months)

- History of premature birth before 35 weeks gestation