# Targeting airway inflammation from concentrated animal feeding operation dust

> **NIH VA I01** · OMAHA VA  MEDICAL CENTER · 2021 · —

## Abstract

Agricultural workers including rural veterans are routinely exposed to aerosolized environmental dust
and are at heightened risk for chronic lung disease due to exaggerated airway inflammatory responses. Our
work has focused on defining inflammatory aspects of organic dust exposures and investigated strategies of
inflammation inhibition to prevent lung injury. Our current proposal aims to identify mechanisms for controlling
lung recovery after damaging airway exposures as both the initiation and resolution of inflammation are critical
in whether disease develops.
 Our pilot data suggests the epidermal growth factor receptor (EGFR) agonist amphiregulin (AREG)
promotes lung repair pathways following exposures to dust extracts (DE) derived from swine concentrated
animal feeding operations. Importantly, our preclinical studies suggest the polyunsaturated fatty acid (PUFA)
docosahexaenoic acid (DHA) obtained by diet may enhance the production of AREG following DE exposure
and protect against DE-induced lung inflammation and injury. Thus, our overall objective is to determine the
contribution of AREG to lung repair pathways following inflammatory organic inhalant exposures. By identifying
regulatory patterns of normative lung repair processes, we aim to identify intervention strategies to improve
lung repair processes in agricultural workers suffering from lung disease. We hypothesize that AREG-
mediated signaling following organic dust exposures promotes lung repair activities, and
dysregulation of these normative lung repair processes leads to lung disease in agriculture workers.
We have developed three specific aims to test this hypothesis:
 Aim 1: Identify the function of AREG in mediating lung repair following organic dust exposures. We
propose to (a) determine the time course of AREG production following DE exposures in vitro and in vivo, (b)
determine the effect of AREG inhibition on DE-induced lung inflammatory and recovery processes in vivo using
our well-established mouse model, (c) identify the effect of exogenous AREG treatment on DE-induced lung
inflammatory and recovery processes in vivo,(d) delineate the functional effects of AREG on human bronchial
epithelial cell (HBEC) wound healing processes during DE exposures using a novel lung scaffolding model.
 Aim 2: Define the mechanisms regulating AREG activities in the lung following organic dust exposures.
We will (a) determine the lung cellular contributions of AREG following DE exposures in vivo, (b) identify the
EGFR-mediated pro-repair signaling events downstream of AREG binding in DE-exposed HBEC, (c) identify
the contributions of tumor necrosis factor-a converting enzyme (TACE) on lung recovery following repetitive
DE exposures in vivo and (d) determine the role of TACE on HBEC wound healing processes in the context of
DE exposures.
 Aim 3: Identify how PUFA regulate AREG-mediated lung repair following organic dust exposures. We
propose to (a) identify the signaling mechanism by which...

## Key facts

- **NIH application ID:** 10130449
- **Project number:** 5I01CX001714-03
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** DEBRA J ROMBERGER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130449

## Citation

> US National Institutes of Health, RePORTER application 10130449, Targeting airway inflammation from concentrated animal feeding operation dust (5I01CX001714-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10130449. Licensed CC0.

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