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Principal Investigator: William James Sheehan
Organization: CHILDREN'S RESEARCH INSTITUTE
Fiscal Year: 2024
Award: $432,791
Funding agency: National Institute of Allergy and Infectious Diseases
Leveraging our institution’s diverse and experienced investigator base, our success in leading collaborative
and single-site randomized clinical trials (RCTs) and mechanistic and observational studies, and our access to
a large population of urban, disadvantaged, and largely minority youth with asthma, we propose the District of
Columbia’s Childhood Asthma in Urban Settings Clinical Research Center (DC CAUSE-CRC). It will implement
network-wide research projects with a multi-disciplinary team of senior and junior investigators bringing diverse
backgrounds in pediatric asthma, allergy and immunology, airway multi-omics, and computational biology. The
proposed clinical leadership has repeatedly succeeded as top enrollers in multi-site asthma research
collaboratives, and our institution houses the required infrastructure to facilitate CAUSE’s collaborative studies.
For our site-specific project, we will build on the prior work of the Inner City Asthma Consortium (ICAC) and
explore the mechanistic and clinical aspects of the paradigm-shifting use of a single dose of omalizumab in the
fall season to prevent exacerbations. Specifically, while providing pilot clinical data for a possible future RCT,
we will examine the interaction of the nasal microbiome and the nasal inflammatory responses during viral
upper respiratory infections (URIs) with and without a single dose of anti-IgE. Working synergistically in
exacerbation-prone urban youth, allergic sensitization, allergen exposure, and rhinovirus (and other viral) URIs
trigger a strong Th2 response and asthma exacerbations that occur most frequently after school begins (the
“September epidemic”). The ICAC has demonstrated that when administered across the entire fall season,
omalizumab reduces the odds of exacerbations by >50%. Given the cost and complexity of this approach,
however, and noting that serum levels of omalizumab rise following subcutaneous injection within a time frame
sufficient to prevent a virally induced exacerbation (7-8 days), we propose an entirely new strategy:
Omalizumab Before Onset of Exacerbations (OBOE). It is a pilot, non-therapeutic, mechanistic RCT of
omalizumab or placebo administered within 72 hours of onset of an URI. Over three fall seasons, OBOE will
randomize at least 100 youth aged 6-17 years with persistent asthma, high atopy, and a recent exacerbation.
We will “capture” their URIs for 90 days after school starts, sampling their nasal airways twice (within 72 hours
of URI onset and again in a window between 7-10 days after URI onset). Our specific aims are: (1) to be
leaders in the collaborative studies of the CAUSE network while fostering the next generation of local
institutional leadership for DC CAUSE-CRC; (2) to determine the relationship among the nasal airway
microbiome, host transcriptome, and Th2 responses in children treated with single dose omalizumab or
placebo at the onset of viral URIs; (3) to determine the relationship between host nasal airway antiviral
interferon-α response with and without omalizumab given at the onset of a viral URI; and (4-exploratory): to
determine the differences in clinical outcomes between intervention and control participants.
Terms: <(IFN) α><(IFN)-α><(IFN)α><0-11 years old><Airway infections><Alferon><Allergens><Allergic><Allergy><Asthma><Asthma in Children><Atopic Allergy><Bacteria><Basic Research><Basic Science><Bio-Informatics><Bioinformatics><Biometrics><Biometry><Biostatistics><Blood><Blood Reticuloendothelial System><Blood Serum><Bronchial Asthma><Caring><Child><Child Youth><Childhood Asthma><Children (0-21)><Clinical><Clinical Data><Clinical Research><Clinical Study><Computational Biology><D.C. Washington><DC Washington><Data><Disadvantaged><Disease><Disorder><District of Columbia><Dose><Ecologic Systems><Ecological Systems><Ecosystem><Epidemic><Event><Fostering><Future><Hour><Hypersensitivity><IFN Alpha><IFN α><IFN-α><IFNa><IFNα><IRB><IRBs><Immune response><Immunological response><Immunology><Infection><Inflammatory Response><Infrastructure><Institution><Institutional Review Boards><Interferon Alfa-n3><Interferon alpha><Interferon-α><Intervention><Intervention Strategies><Investigational Drugs><Investigational New Drugs><Investigators><Laboratories><Leadership><Leukocyte Interferon><Lymphoblast Interferon><Lymphoblastoid Interferon><Microbe><Modeling><Molecular><Moraxella><Morbidity><Morbidity - disease rate><Nasal><Nasal Passages Nose><Nose><Obesity><Observation research><Observation study><Observational Study><Observational research><Oral><Outcome><Participant><Patients><Pediatric asthma><Pharmacies><Pharmacy facility><Placebos><Production><Protocol><Protocols documentation><R-Series Research Projects><R01 Mechanism><R01 Program><RNA Seq><RNA sequencing><RNAseq><Randomized><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Researchers><Respiratory Infections><Respiratory System, Nose, Nasal Passages><Respiratory Tract Infections><Rhinovirus><Risk><Role><Sampling><Schools><Seasons><Secure><Serum><Severities><Sham Treatment><Site><Streptococcus><Subcutaneous Injections><System><Time><Up-Regulation><Upper Respiratory Infections><Upper Respiratory Tract Infection><Upregulation><Urban Community><Urban Population><Viral><Viral Diseases><Virus><Virus Diseases><Wheezing><Work><Youth><Youth 10-21><adiposity><adolescent minority><aged><airway microbiome><allergen response><allergic response><allergy response><anti-IgE><anti-IgEid><asthma attack><asthma exacerbation><asthma prevention><atopic triad><atopy><base><bases><computer biology><corpulence><cost><cytokine><data management><exacerbation in asthma><exacerbation prone asthma><exacerbation prone asthmatic><experience><falls><global gene expression><global transcription profile><healthy volunteer><high risk><host response><immune system response><immunoresponse><improved><inner city><innovate><innovation><innovative><interventional strategy><kids><metatranscriptome><microbiome><minority children><minority youth><multidisciplinary><multiomics><multiple omics><nasal microbiome><next generation><omalizumab><panomics><participant retention><pediatric minority><prevent><preventing><randomisation><randomization><randomized, clinical trials><randomly assigned><recruit><research study><respiratory microbiome><respiratory tract microbiome><response><sham therapy><sinonasal microbiome><social role><subdermal injection><success><transcriptome><transcriptome sequencing><transcriptomic sequencing><transcriptomics><urban children><urban environment><urban group><urban individual><urban people><urban setting><viral infection><virus infection><virus-induced disease><wheeze><young minority><youngster>