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Multi-omics of the Frequent Exacerbator Asthmatic

Award Number: U01AI159087
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/09/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Multi-omics of the Frequent Exacerbator Asthmatic - ABSTRACT Asthma is a common, complex and costly pediatric chronic condition in the U.S., resulting in nearly 2 million acute-care visits and $82 billion in overall costs each year. Children of low-income families in urban communities have the highest prevalence of asthma and the greatest disparities in asthma morbidity and mortality. In Hamilton County, OH, over 36,000 children have asthma, >14,000 of whom are Medicaid- insured with a 10-fold higher rate of hospitalization. Asthma exacerbations, acute episodes of increased asthma symptoms and deteriorations in lung function, are a major cause of stress for patients and families. While exacerbations are a prominent feature of poorly controlled and severe asthma, exacerbation rates can be high even in patients with mild asthma and asthma exacerbation frequency can remain unchanged despite intensive controller therapy. Indeed, pediatric studies have revealed that exacerbations continue to occur despite good baseline symptom control. A frequent exacerbator phenotype of asthma (defined by 2 or more exacerbations/year), has been described, but little is known about this asthma subgroup, which disproportionately affects urban populations and is responsible for considerable asthma morbidity and healthcare costs. No specific clinical characteristics can reliably discriminate between frequent and nonfrequent exacerbators highlighting the need for systems level approaches. Our center-specific project will fill this gap in understanding. Our preliminary data reveal differentially expressed and differentially methylated genes in the nasal epithelial of children who are frequent exacerbators and highlight biologic pathways that implicate distinct mechanisms that underlie the frequent exacerbator phenotype. We will test the hypothesis: the frequent exacerbator is a distinct endotype of asthma that is characterized by host nasal epithelial transcriptomic and/or DNA methylomic patterns that distinguish the frequent exacerbator from asthmatic children who are not frequent exacerbators, and that these patterns are, in part, triggered by distinct nasal microbial patterns. We propose an innovative strategy utilizing multiple systems-based approaches that layer host nasal biome and methylome patterns with nasal epithelial transcriptomics taken during an acute exacerbation (before administration of steroids). We are uniquely poised to conduct this study due to the tremendous infrastructure that we have established as part of the Ohio Pediatric Asthma Repository, and our multidisciplinary team. The overall objective of our studies is to improve the lives of children with asthma from low-income families who live in urban communities. We propose to 2 aims: (1) To contribute to the overall CAUSE goals by conducting network-wide CAUSE clinical research projects and participating in the CAUSE Steering Committee and other network functions; (2) To conduct a center- specific project aligned with CAUSE goals focused on the frequent exacerbator asthma phenotype.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $452,000 )
2025	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	5	4/14/2025	NON-COMPETING CONTINUATION	$452,000
														Subtotal = $452,000

Issue Date FY: 2024 ( Subtotal = $452,000 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	4	2/14/2024	NON-COMPETING CONTINUATION	$406,800
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	001	4	4/16/2024	NON-COMPETING CONTINUATION	$45,200
														Subtotal = $452,000

Issue Date FY: 2023 ( Subtotal = $452,000 )
2023	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	3	3/17/2023	NON-COMPETING CONTINUATION	$452,000
2023	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	001	3	4/10/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $452,000

Issue Date FY: 2022 ( Subtotal = $452,000 )
2022	2022	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	2	3/23/2022	NON-COMPETING CONTINUATION	$452,000
														Subtotal = $452,000

Issue Date FY: 2021 ( Subtotal = $452,000 )
2021	2021	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	1	4/9/2021	NEW	$452,000
														Subtotal = $452,000

Grand Total All Awards = $2,260,000

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Multi-omics of the Frequent Exacerbator Asthmatic

Award Number: U01AI159087

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/09/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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