# The Role of Nasal Mucosal Immunity and Microbiome on the Frequent Exacerbation Phenotype of COPD

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $712,444

## Abstract

PROJECT SUMMARY/ABSTRACT
Chronic obstructive pulmonary disease (COPD) is a progressive pulmonary disease characterized by frequent
episodes of acute deterioration termed acute exacerbations of COPD (AECOPD). The underlying biological
mechanisms and risk profiles contributing to AECOPD are poorly understood. The nasal mucosal environment,
including the inflammatory state and nasal microbiome, play a role in host defenses against viral infections.
Susceptibility to viral infections, a trigger of AECOPD, is a potential mechanism for the COPD frequent
exacerbator phenotype. Our research group has established approaches to rigorously characterize and quantify
the nasal mucosal immune environment and microbiome, as well as determine the functional status of the nasal
immune environment with a controlled Live Attenuated Influenza Vaccine (LAIV) exposure. Our overall objective
is to determine the immune alterations and functional implications of changes in the nasal immune environment
and microbiome present in individuals with frequent AECOPD. We hypothesize that dysfunctional nasal immunity
underlies the frequent AECOPD phenotype and therefore presents a novel mechanism of increased AECOPD
risk. We hypothesize that these immune alterations will impact responses to controlled viral infection and could
predict the course of naturally occurring AECOPD. We will define the nasal immune environment (Aim 1) and
microbiome (Aim 2) of frequent exacerbators, infrequent exacerbators, and healthy non-smokers, using cluster
analyses to define the nasal “biological fingerprint” of the frequent AECOPD phenotype. Through longitudinal
assessments embedded in these Aims we will define the variations of these measures during stable state and
during AECOPD. We will then use a Live Attenuated Influenza Vaccine (LAIV) model to determine the functional
implications of differences in the respiratory immune environment of frequent and infrequent exacerbators during
a controlled viral challenge (Aim 3). Successful completion of these aims will lead to the first rigorous
characterization of the nasal mucosal and microbiome changes associated with frequent exacerbators of COPD,
validate these findings in a controlled experimental setting, and advance a novel hypothesis that the frequent
exacerbator phenotype arises from altered nasal immune responses and microbiome constitution.

## Key facts

- **NIH application ID:** 10829906
- **Project number:** 5R01HL150081-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Michael Bradley Drummond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $712,444
- **Award type:** 5
- **Project period:** 2021-05-08 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829906

## Citation

> US National Institutes of Health, RePORTER application 10829906, The Role of Nasal Mucosal Immunity and Microbiome on the Frequent Exacerbation Phenotype of COPD (5R01HL150081-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10829906. Licensed CC0.

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