# Atopic dermatitis: mechanisms of disease progression

> **NIH NIH U01** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $539,133

## Abstract

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 rhini...

## Key facts

- **NIH application ID:** 10379962
- **Project number:** 5U01AI152034-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Gurjit K. Khurana Hershey
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $539,133
- **Award type:** 5
- **Project period:** 2020-04-20 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10379962

## Citation

> US National Institutes of Health, RePORTER application 10379962, Atopic dermatitis: mechanisms of disease progression (5U01AI152034-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10379962. Licensed CC0.

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