Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy
Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy
Asthma is a growing problem, especially in children. It causes frequent wheezing, shortness
 of breath, chest tightness, and cough. A cold that is caused by a virus (viral cold) can
 sometimes make asthma symptoms worse. This study will help investigators learn about the way
 colds are related to asthma attacks among children who need higher amounts of medications to
 control their asthma. Investigators want to learn why viral colds sometimes cause asthma
 attacks and other times do not by studying the immune system response in samples taken from
 the nose and blood.
This study is a prospective, longitudinal, nested case-control study designed to identify
 changes in gene transcription predictive of and associated with asthma exacerbations in
 children ages 6 to 17 years with difficult-to-control, exacerbation-prone asthma.

 Participants will be followed prospectively for the onset of a cold and a subsequent asthma
 exacerbation. An internet-based asthma and cold symptom diary will be accessed by
 participants using a hand-held device. When the participant reports development of a cold, a
 clinic visit will be scheduled as soon as possible (within 48 hours of cold symptom onset) to
 collect blood and nasal samples. A second clinic visit will occur 4-6 days from the onset of
 cold symptoms to obtain samples after the initial cold, but prior to the use of systemic
 corticosteroids. Participants will be followed for up to two colds or approximately 6 months
 after Visit 0, whichever comes first.
Inclusion Criteria:

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

 -  Have a primary place of residence in one of the pre-selected recruitment census tracts
 as outlined in the Inner City Asthma Consortium (ICAC) Manual of Procedures (MOP);

 -  Have a diagnosis of asthma made by a clinician >1 year prior to recruitment;

 -  Have had at least 2 asthma exacerbations in the prior year, defined as a requirement
 for systemic corticosteroids and/or hospitalization;

 -  Have the following requirement for asthma controller medication at the Screening and
 Enrollment Visit (Visit 0) according to the MEDS program[4, 2]:

 -  For participants aged 6 to 11 years, treatment with at least fluticasone 250 mcg
 1 puff twice daily or its equivalent;

 -  For participants ages12 years and older, treatment with at least Advair 250/50
 mcg 1 puff twice daily or its equivalent.

 -  Have peripheral blood eosinophils >=150 per mm^3. Results can be obtained from
 participation in a previous ICAC study if obtained within 6 months of the Screening
 and Enrollment Visit (Visit 0);

 -  Currently a non-smoker;

 -  Parent/legal guardian is willing to sign the written informed consent;

 -  Participant is willing to sign the assent form as per central Institutional Review
 Board (IRB) guidelines;

 -  Has some form of insurance that covers costs of usual care asthma control and rescue
 medications at the Screening and Enrollment Visit (Visit 0).

 Exclusion Criteria:

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

 -  Are currently pregnant or lactating;

 -  Are currently receiving treatment with anti-immunoglobulin E (anti-IgE) therapy or
 have had anti-IgE therapy in the previous 3 months prior to screening;

 -  Are currently receiving immunotherapy;

 -  Have clinically significant abnormalities on complete blood count (CBC) with
 differential as determined by the site study clinician. Results can be obtained from
 participation in a previous ICAC study [including Registry for Asthma Characterization
 and Recruitment 2 (RACR2), NCT02513264} if obtained within the last 6 months of Visit
 0;

 -  Was treated with systemic corticosteroids for any medical condition including an
 asthma exacerbation within the 2 weeks prior to Visit 0;

 -  Have had a cold in the previous 7 days;

 -  Are currently participating in an asthma-related pharmaceutical study or intervention
 study or has participated in another asthma-related pharmaceutical study or
 intervention study in the previous 4 weeks prior to recruitment;

 -  Are currently requiring greater than fluticasone 500 mcg bid plus long-acting beta
 agonist (LABA) 1 puff twice daily or its equivalent and\or individuals using oral
 corticosteroids daily or every other day at Visit 0.

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

 -  Have any medical illnesses that in the opinion of the investigators would a.) increase
 the risk the participant 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 Willebrands disease, sickle cell
 disease, cerebral palsy, rheumatoid arthritis, lupus, psoriasis, hyperimmunoglobulin E
 syndrome, parasite infections, Wiskott-Aldrich syndrome, or allergic bronchopulmonary
 aspergillosis.

 -  Have concurrent medical problems that would require systemic corticosteroids (other
 than for treatment of an asthma exacerbation) or other immunomodulators during the
 study;

 -  Currently have diagnosed cancer, are currently being investigated for possible cancer,
 or have a history of cancer;

 -  Have plans to move from the area during the study period;

 -  Do not primarily speak English (or Spanish at clinical sites with Spanish speaking
 staff);

 -  Have a primary caretaker who does not speak English (or Spanish at clinical sites with
 Spanish-speaking staff; not applicable if participant is able to provide consent);

 -  Are a foster child;

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

 -  Are not able to perform pulmonary function tests;

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

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