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Atopic dermatitis: mechanisms of disease progression

Award Number: U01AI152034
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: 04/20/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Atopic dermatitis: mechanisms of disease progression - PROJECT SUMMARY Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that affects up to 20% of children worldwide. AD has been highlighted as the first step in the “atopic march”, whereby AD typically predates the development of other allergic disorders. Atopic sensitization and food allergy have been reported to be precursors of AD progression to respiratory allergy, however recent data indicate that the mechanisms are far more complex. The National Institute of Allergy and Infectious Diseases recently convened a workshop titled ``Atopic dermatitis and the atopic march: mechanisms and interventions''6 and they concluded that only about 3% of children follow what has been conventionally referred to as the atopic march. They stated that a new prospective cohort study that uses multiparameter approaches to define phenotypic/endotypic subgroups of AD and to predict AD outcomes is needed. As part of our U19 Asthma and Allergic Diseases Cooperative Research Center (AADCRC) funded by the National Institute of Allergy and Infectious Diseases, we have built the first mechanistic longitudinal cohort study of pediatric atopic dermatitis (AD), the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH). MPAACH is the first early life prospective cohort of children with AD in the US and incorporates extensive evaluations of skin, gut, airway and peripheral blood, as well as the use of multiparameter approaches to define phenotypic and endotypic subgroups of AD. Thus far, we have enrolled 537 children. The goals of the MPAACH cohort are to define AD phenotypes and endotypes, dissect the mechanisms that contribute to the progression of AD to other allergic disorders (food allergy, allergic rhinitis, asthma), and delineate the immunologic, skin, biome, genetic/epigenetic/genomic, physiologic, and environmental factors that promote the development of allergic comorbidities in children with AD. To enable mechanistic studies, extensive biospecimens are collected from lesional and non-lesional skin. We have 20 years of experience and expertise in conducting large cohort studies and are uniquely positioned to contribute to ADRN and SUNBEAM due to our current cohorts and clinical research infrastructure, as well as our experienced and diverse large staff, who are experts in recruitment, regulatory affairs, conducting visits, collection and processing of biospecimens, and execution and reporting of studies. Based on our strong preliminary data from MPAACH, we are proposing 3 CRC-specific research projects to address our overarching hypothesis is that visually normal skin may have skin barrier dysfunction that becomes clinically evident (lesional) or remains subclinical (no lesions), but in both cases the skin barrier dysfunction coupled with dysbiosis of skin microbiome triggers alarmins, which initiates an immunologic cascade that promotes the subsequent development of allergic disease including food allergy, asthma and allergic rhinitis.


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: 2026 ( Subtotal = $224,999 )
2026	2026	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	001	7	4/1/2026	NON-COMPETING CONTINUATION	$224,999
2026	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	6	3/24/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $224,999

Issue Date FY: 2025 ( Subtotal = $224,999 )
2025	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	6	3/24/2025	NON-COMPETING CONTINUATION	$224,999
														Subtotal = $224,999

Issue Date FY: 2024 ( Subtotal = $224,999 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	5	3/29/2024	NON-COMPETING CONTINUATION	$224,999
														Subtotal = $224,999

Issue Date FY: 2023 ( Subtotal = $224,999 )
2023	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	4	3/24/2023	NON-COMPETING CONTINUATION	$224,999
														Subtotal = $224,999

Issue Date FY: 2022 ( Subtotal = $539,133 )
2022	2022	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	001	3	7/20/2022	NON-COMPETING CONTINUATION	$314,134
2022	2022	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	3	3/24/2022	NON-COMPETING CONTINUATION	$224,999
														Subtotal = $539,133

Issue Date FY: 2021 ( Subtotal = $224,999 )
2021	2021	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	2	3/30/2021	NON-COMPETING CONTINUATION	$224,999
														Subtotal = $224,999

Issue Date FY: 2020 ( Subtotal = $224,999 )
2020	2020	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Allergy and Infectious Diseases Research	000	1	4/20/2020	NEW	$224,999
														Subtotal = $224,999

Grand Total All Awards = $1,889,127

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Atopic dermatitis: mechanisms of disease progression

Award Number: U01AI152034

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: 04/20/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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