# Mechanisms that Direct Airway Remodeling in Obese Asthma

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $161,000

## Abstract

Project Summary
Asthma is more prevalent in adult females than males. In addition, nearly 40% of patients with asthma in the US
are obese. Adult female obese asthma patients experience increased asthma severity with diminished
responsiveness to standard medications compared to male and lean asthma patients. Obesity is associated
with inflammatory and metabolic changes that contribute to asthma pathobiology. Specifically, systemic
metabolic changes in the obese patient, including increased levels of leptin, a pro-inflammatory mediator
secreted by adipose tissue, augments pathogenic processes in asthma by acting directly on structural cells in
the airway. Airway remodeling describes airway structural changes in asthma, including airway fibrosis, that can
result in permanent airway obstruction. The mechanisms directing airway remodeling in female obese asthma
are particularly poorly understood. Our preliminary data show that airway fibrosis is significantly elevated in
obese female patients with allergic asthma compared to male obese allergic asthma patients. Furthermore, leptin
augments chronic allergen-induced airway fibrosis, small airways resistance and eosinophilic inflammation in
female mice compared to male mice. Our overarching hypothesis is that, in obese asthma, males are protected
from the combined effects of chronic leptin and allergen exposure on airway pathology compared to females.
We further hypothesize that adipose tissue in obese female allergic asthmatics secretes increased leptin and
pro-fibrotic growth factors than their male counterparts and that these changes contribute to airway inflammation
and fibrosis in allergic asthma through a mechanism requiring PPARg inhibition. We will test this hypothesis by
confirming the contribution of biological sex to pathologic airway and adipose responses in a mouse model of
chronic obesity and allergic airways disease (Aim 1), and by testing the sex-specific influence of visceral adipose
tissue-derived secreted factors on airway fibroblast cellular responses and lung function in human obese asthma
(Aim 2). The studies described in this proposal will extend the studies proposed in our original R01 to specifically
address sex-specific differences in obese asthma and they will address two objectives listed in the strategic
goals of the 2019-2023 Trans-NIH Strategic Plan for Women’s Health Research: to discover basic biological
differences between females and males and investigate the influence of sex and gender on disease prevention,
presentation, management and outcomes. Successful completion of these Aims will increase our understanding
of the unique cellular and metabolic mechanisms directing the pathobiology of female obese asthma.

## Key facts

- **NIH application ID:** 10093686
- **Project number:** 3R01HL130234-04S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jennifer L. Ingram
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $161,000
- **Award type:** 3
- **Project period:** 2017-09-18 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10093686

## Citation

> US National Institutes of Health, RePORTER application 10093686, Mechanisms that Direct Airway Remodeling in Obese Asthma (3R01HL130234-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10093686. Licensed CC0.

---

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