# Phenotypic and biological features of mucus plugs in asthma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $663,718

## Abstract

Project Summary / Abstract
Our published data reveals that semi quantitative mucus plug scores strongly associate with measures of airway
type 2 inflammation and airflow obstruction in asthma. We have now developed novel approaches to move from
a semi-quantitative mucus plug score to detailed quantitative mucus plug phenotyping (mucus plug number,
size, and location), and this technology allows us to more deeply explore mucus plug biology in asthma. Our
renewal grant application will continue to leverage CT lung images and airway biospecimen resources from the
SARP-3 cohort, take advantage of an imaging team built by Dr Fahy to explore airway mucus plug phenotypes
using CT lung images, and continue an ongoing collaboration between Dr Fahy’s and Dr Seibold’s labs to jointly
tackle disease mechanisms in asthma. Aim 1 will explore relationships between airway mucus plugs, type 2
inflammation and airflow obstruction. Our studies of mucus plugs and type 2 inflammation will include analysis
of airway mucus plugs in SARP-3 patients before and after they were started on therapeutic proteins targeting
the type 2 pathway. Our studies of mucus plugs and airway location are designed to determine the number of
mucus plugs and the airway sizes that are most consequential for airflow limitation. Aim 2 will determine if
treatment with inhaled N-acetylcysteine (NAC) improves airflow in mucus-high asthma. NAC is mucolytic
because it cleaves the excessive disulfide bridges between mucin polymers that increase airway mucus gel
elasticity in asthma. Our clinical trial will directly test the hypothesis that mucus plugs cause airflow limitation in
asthma and determine the influence of mucus plug phenotypes on response to mucolytic treatment. Aim 3 will
determine the role of ITLN1 in the pathophysiology of airway mucus plugs in asthma. Intelectin-1 (ITLN1) is an
epithelial cell protein that is upregulated by IL-13 (a type 2 cytokine), and our preliminary data show that a eQTL
variant in ITLN-1 modifies risk of mucus plugging in asthma. This provided impetus for us to explore mechanisms
of ITLN-1 mediated mucus pathology in bench experiments. Our aims have specific hypotheses, are supported
by robust preliminary data, and are enabled by the application of state of the art imaging, computer vision, and
cellular and molecular methodologies. Our research promises to advance understanding about mucus plug
biology in patients with severe asthma and our data will inform drug development for mucus plugs and the
potential utility of therapeutic bronchoscopy. Most importantly, our CT mucus phenotyping biomarkers will
provide the field with much needed predictive and monitoring biomarker for mucus-high asthma.

## Key facts

- **NIH application ID:** 10654049
- **Project number:** 5R01HL080414-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** John V Fahy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $663,718
- **Award type:** 5
- **Project period:** 2005-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10654049

## Citation

> US National Institutes of Health, RePORTER application 10654049, Phenotypic and biological features of mucus plugs in asthma (5R01HL080414-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10654049. Licensed CC0.

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