# Obese Allergic Asthma and the Impact of Weight Loss on Airway Epithelial Function

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $775,680

## Abstract

ABSTRACT
The majority of severe asthmatics in the U.S. are obese, and among obese asthmatics, those with early-onset
allergic (EOA) disease suffer with particularly severe disease. Relationships between metabolic, immunologic,
and physiologic alterations, and how they are affected by weight loss, remain poorly understood in EOA obese
asthma. Especially striking is a gap in knowledge of how adipose-derived mediators affect the lung to cause
alterations in airway epithelial mitochondrial function that augment baseline and allergen-induced cytokine
production to cause the structural and physiologic lung alterations characteristic of obese allergic asthma. We
hypothesize that circulating factors from visceral adipose tissue of early onset allergic (EOA) obese asthmatics
cause mitochondrial dysfunction in airway epithelial cells that increases sensitivity to allergenic triggers, and
the release of soluble factors that amplify EOA asthma in obesity, events that are reversed by weight loss. We
will address this hypothesis through a combination of studies using materials collected from subjects enrolled
in a longitudinal study of (EOA) asthmatics undergoing bariatric surgery, as well as by using novel mouse
models.
In Specific Aim #1, we will determine the effects of weight loss on the response to in vivo allergen challenge in
obese allergic asthmatic patients and how this relates to changes in mitochondrial reactive oxygen species and
calcium handling affecting cytokine response to allergen in airway epithelial cells.
In Specific Aim #2, we will determine which circulating mediators elevated in obese asthmatics, as well as
factors produced from visceral adipose tissue, induce cytokine secretion from airway epithelium. We will
quantitate specific proteins in the plasma and made by adipose tissue, then culture human bronchiolar
epithelial (HBE) cells and nasal epithelial cells with plasma or adipose tissue-conditioned media in the absence
and presence of HDM extract to identify secreted epithelial-derived cytokines. We will also analyze primary
nasal epithelial cells from normal weight and obese asthmatics prior to and following bariatric surgery to
determine differences in cytokine expression and production. Finally, we will neutralize airway epithelial-
activating mediators in the plasma to determine the impact on secretion of epithelial factors.
In Specific Aim #3, we will determine the consequences of adipose-activated airway epithelial cells on features
of asthma using novel mouse models of diet-induced obesity and surgical or dietary weight loss, as well as the
in vivo neutralization of adipose- and epithelial-derived factors, to examine the impact on allergic asthma
associated with obesity. Airway epithelial cells will be assessed for alterations in mitochondrial metabolism and
the impact of mediator inhibition on lung structure and methacholine responsiveness will be assessed.
These clinical and preclinical studies will provide a better understand...

## Key facts

- **NIH application ID:** 9991894
- **Project number:** 5R01HL133920-05
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Anne E Dixon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $775,680
- **Award type:** 5
- **Project period:** 2016-08-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991894

## Citation

> US National Institutes of Health, RePORTER application 9991894, Obese Allergic Asthma and the Impact of Weight Loss on Airway Epithelial Function (5R01HL133920-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9991894. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*