# Understanding airway mucus dysfunction in population-based studies

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $611,176

## Abstract

Project Summary/Abstract
Mucus dysfunction plays a critical role in airway diseases like chronic bronchitis (CB) and chronic obstructive
pulmonary disease (COPD). COPD affects approximately 29 million people in the US and is the third leading
cause worldwide. The public health and clinical relevance of “mucus dysfunction” are better understood when
one focuses on the clinical manifestations of this process —chronic cough and phlegm and chronic mucus
hypersecretion/CB. Up to 32% of community-living individuals report chronic respiratory symptoms and present
with normal lung function. The presence of chronic symptoms in these individuals is associated with a
substantially increased risk of future hospitalization and mortality.
In this proposal, we will use an objective, reproducible assessment of mucus dysfunction. We will identify and
score mucus plugging on chest computed tomography (CT) scans from community-living individuals
participating in two population-based studies, the Framingham Heart Study (FHS) and Coronary Artery Risk
Development in Young Adults (CARDIA). In Aim 1, we will determine the clinical relevance of CT-based mucus
plugging. We will evaluate the associations of mucus plugging with lung function, respiratory symptoms, and
chronic bronchitis (Aim 1a); and examine whether 5-yr. Persistent CT-based mucus plugging is associated with
the decline in FEV1 and future COPD (Aim 1b). In Aim 2, we will examine whether modifiable factors affect CT-
based mucus plugging. We will determine whether air pollution and marijuana smoking are associated with
increased odds of CT-based mucus plugging and define whether cardiorespiratory fitness is related to
decrease mucus plugging. Finally, in Aim 3, we will determine genetic resilience/susceptibility to mucus
dysfunction. We will use CT data from the FHS and CARDIA cohorts and genome-wide sequencing data from
the TOPMed initiative to identify common and rare variants associated with CT-based mucus plugging.
This study will increase our understanding of the clinical implications of an imaging-based mucus dysfunction
phenotype at the population level, providing a tangible target for the interception and prevention of chronic
airway disease while identifying susceptibility, risk, and protective factors for this process.

## Key facts

- **NIH application ID:** 10894886
- **Project number:** 5R01HL164824-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Alejandro Diaz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $611,176
- **Award type:** 5
- **Project period:** 2022-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894886

## Citation

> US National Institutes of Health, RePORTER application 10894886, Understanding airway mucus dysfunction in population-based studies (5R01HL164824-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894886. Licensed CC0.

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