# Examining Mechanisms of Synergy between Asthma Exacerbations and RV Infection

> **NIH NIH K08** · ARKANSAS CHILDREN'S HOSPITAL RES INST · 2020 · $193,320

## Abstract

PROJECT SUMMARY/ABSTRACT
 Dr. Kennedy is an Allergist/Immunologist at the University of Arkansas for Medical Sciences Departments
of Pediatrics and Internal Medicine and a young investigator at Arkansas Children's Hospital Research
Institute. A three-pronged mission to perform cutting-edge research, provide outstanding clinical care, and
pursue educational excellence summarizes his overarching academic career objectives. His training and
experience have enabled him to develop the skills and insight necessary to provide high-quality care to
patients with asthma and allergic disorders, as well as providing a foundation for human subjects research.
The primary objective for this mentored career development award proposal is to further Dr. Kennedy's
knowledge and abilities in basic and translational investigation. This objective will specifically enable him to
achieve my long-term research goals, including: 1) understanding the immune responses accounting for
synergy between asthma exacerbations and infection with RV, 2) developing biomarkers of asthma
disease severity and exacerbation following RV infection, and 3) translating this research into clinically
relevant prevention and intervention strategies for patients with asthma.
 Asthma is prevalent in ~12% of the US population, and RV is recognized as the most important virus
producing the common cold syndrome worldwide. Unlike patients without asthma who generally develop upper
respiratory symptoms during colds, asthmatics with an RV infection may exhibit lower respiratory symptoms
(e.g., cough, wheeze, shortness of breath). In fact, RV is associated with 60% to 80% of asthma exacerbations
in children requiring treatment in the emergency department9-11. Despite such strong relationships, a significant
knowledge gap exists with regards to the mechanisms whereby RV exacerbates asthma symptoms. Recent
developments in cytokine biology have increasingly emphasized the importance of respiratory epithelial-
derived cytokines in creating the milieu that promotes the evolution of allergic immune responses. The overall
goal of this proposal is to understand the association between RV infection and the epithelial immune
responses that bridge the allergic response to infection in asthmatics. We hypothesize that RV infection
modulates epithelial cytokine expression [Interleukin (IL)-25 and thymic stromal lymphopoietin (TSLP)]
in asthmatics with bias towards an allergic inflammatory response, and this underlies infection-
mediated increases airway hyper-responsiveness (AHR). To address this hypothesis, we have a unique
approach that brings together an in vivo study of epithelial-derived cytokines from subjects with asthma
exacerbations, primary epithelial cell cultures, and a novel precision cut lung slice (PCLS) explant system
allowing comparison of RV infections in asthmatic and non-asthmatic tissues. Using a cross-sectional design in
a pediatric emergency department, we will compare cytokine signatures withi...

## Key facts

- **NIH application ID:** 9914076
- **Project number:** 5K08AI121345-05
- **Recipient organization:** ARKANSAS CHILDREN'S HOSPITAL RES INST
- **Principal Investigator:** Joshua Kennedy
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,320
- **Award type:** 5
- **Project period:** 2016-05-15 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914076

## Citation

> US National Institutes of Health, RePORTER application 9914076, Examining Mechanisms of Synergy between Asthma Exacerbations and RV Infection (5K08AI121345-05). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9914076. Licensed CC0.

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