Asthma Phenotypes in the Inner City

Asthma is a complex, heritable disease that affects more than 11.2% of the U.S. population,
which represents approximately 9 million children and 23 million adults. Although the
underlying characteristics of asthma exist in virtually all patients, the clinical
expression of the disease and response to treatment are highly variable.

The purpose of this study is to identify characteristics that will discriminate
Difficult-to-Treat from Easy-to-Treat asthma in a defined inner-city population adherent to
study-directed asthma treatment and management.

Inclusion Criteria:

Participants who meet all of the following criteria are eligible for enrollment.
Participants may be reassessed if not initially eligible. Participants are eligible if
they:

- Are male or female ages 6-17 years, inclusive, at recruitment;

- Have a physician diagnosis of asthma;

- Have had ≥ 2 episodes of short-acting beta-agonist administration within the past 12
months, exclusive of use associated with exercise-induced symptoms;

- Have a primary place of residence located in one of the pre-selected recruitment
census tracts as defined in the APIC Manual of Operations;

- Meet pretreatment eligibility requirements for study enrollment (acceptable medical
history and physical examination results);

- Have a parent or legal guardian who is willing to sign the written Informed Consent
prior to initiation of any study procedure;

- Are willing to sign the assent form, if age appropriate;

- Have medical insurance at the Screening Visit. Coverage must be in effect from
Screening through Enrollment in order to be enrolled.

Exclusion Criteria:

Participants who meet any of the following criteria are not eligible for enrollment but
may be reassessed. Participants are ineligible if they:

- Have had ≥ 2 life-threatening asthma exacerbations in the last 2 years requiring
intubation or mechanical ventilation, or resulting in a hypoxic seizure;

- Are pregnant or lactating. (Females of child-bearing potential must remain abstinent
or use a medically acceptable birth control method (e.g. oral, subcutaneous,
mechanical, or surgical contraception) throughout the study. This is not for safety,
but because it may be difficult to assess asthma control since lung function may
change, making it difficult to interpret outcome measures);

- Will not allow the study clinician to manage their disease for the duration of the
study or who are not willing to change their asthma medications to follow the
protocol;

- Are unable to use a metered-dose inhaler (MDI) for administration of a beta-agonist
rescue medication or use a dry powder inhaler (Diskus®) for the administration of
asthma controller regimens;

- Are currently receiving hyposensitization therapy or have received hyposensitization
therapy to any allergen in the past year prior to recruitment;

- Are currently participating in an asthma-related pharmaceutical study or intervention
study or who have participated in another asthma-related pharmaceutical study or
intervention study in the month prior to recruitment;

- Do not sleep at least 4 nights per week in the same home;

- Have a sibling or other person living in the same home enrolled in the study;

- Live with a foster parent; not applicable if participant is able to provide consent;

- Do not have access to a phone (needed for scheduling appointments);

- Who are currently taking, or who have taken any of the following medications within 4
weeks of the Screening Visit (Visit -1): Monoamine oxidase inhibitors (phenelzine,
tranylcypromine); Tricyclic and tetracyclic antidepressants; beta adrenergic blocker
drugs (both oral and topical); Anticonvulsants (carbamazepine, phenobarbital,
phenytoin, mephobarbital, primidone, ethosuximide, methsuximide, felbamate,
gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate,
valproic acid, divalproex sodium, zonisamide); Protease inhibitors (ritonavir,
indinavir, nelfinavir); Calcium channel blockers (verapamil, diltiazem); Modafinil;
Tamoxifen; non-nucleoside reverse transcriptase inhibitors; Macrolide antibiotics*
(erythromycin, clarithromycin, dirithromycin, troleandomycin); chloramphenicol;
nefazodone; aprepitant; St John's Wort; Rifampin*; Azole Antifungals* (ketoconazole,
fluconazole, itraconazole); Sibutramine* ; bergamottin (constituent of grapefruit
juice) (*may be rescreened if this therapy is short-lived);

- Should not be included in the study for any other reason, according to the
investigator's discretion. This would include when, in the judgment of the
investigator, the clinical care of the participant would be compromised by the
treatment algorithm;

- Are receiving treatment with omalizumab, or have had omalizumab treatment within
three months prior to screening;

- Are not able to perform spirometric pulmonary function tests (PFTs);

- Are not adherent to the controller medication between Visit 1 and Visit 0 (defined as
medication use less than 50%, (Ref: Section 6.6 in study protocol- determining
treatment adherence);

- Participants who meet any of the following criteria are not eligible for enrollment
and may not be reassessed. Participants are ineligible if they:

- Do not primarily speak English (or Spanish at centers with Spanish speaking
staff). Exclusion also applies to the child's caretaker;

- Plan to move from the area during the study period (13 months);

- Have any medical illnesses that in the opinion of the investigators would a.)
increase the risk the subject would incur by participating in the study; b.)
interfere with the measured outcomes of the study; or c.) interfere with the
performance of the study procedures.

Examples of such diseases are: phenylketonuria, cystic fibrosis, bronchiectasis, type 1
diabetes, hemophilia, Von Willebrand disease, sickle cell disease, cerebral palsy,
rheumatoid arthritis, lupus, psoriasis, hyperimmunoglobulin E syndrome, parasite
infection(s), Wiskott-Aldrich Syndrome or allergic bronchopulmonary aspergillosis;

- Have known hypersensitivity to any of the medications that will be used for the
treatment of asthma or rhinitis;

- Have a current, severe hypersensitivity to milk;

- Have a current diagnosis of cancer, are currently being investigated for possible
cancer, or who have a history of cancer.