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Rapid Viscoelastic Characterization of Airway Mucus Using a Benchtop Rheometer

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Mucus plugs-associated gene expression identifies pathophysiology shared with chronic bronchitis.

Whitney N Souery¹, Ehab Billatos¹, Rim Elalami²

¹Section of Computational Biomedicine, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States.

American Journal of Respiratory and Critical Care Medicine

|October 10, 2025

Summary

Gene expression patterns in mucus plugs reveal distinct epithelial and immune pathways. These findings offer insights into mucus pathology in chronic obstructive pulmonary disease (COPD) and chronic bronchitis symptoms.

Keywords:

COPD mucus dysfunction transcriptomics

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Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins

Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins

Published on: June 14, 2016

Area of Science:

Pulmonary Medicine
Molecular Biology
Genomics

Background:

Mucus plug formation and chronic bronchitis are key features of mucus pathology in chronic obstructive pulmonary disease (COPD).
Understanding the genetic underpinnings of mucus pathology is crucial for elucidating its pathogenesis.

Purpose of the Study:

Investigate gene expression alterations in individuals with mucus plugs.
Identify associated biological pathways.
Correlate mucus plug-related gene expression with clinical features of other mucus pathologies.

Main Methods:

Utilized bulk RNA-sequencing on bronchial brush samples from 290 participants (204 discovery, 86 validation) in the "Detection of Early Lung Cancer Among Military Personnel 2" study.
Quantified mucus plugging via chest CT scans and performed correlative analyses to identify differentially expressed genes.
Examined associations between gene expression and chronic bronchitis symptoms.

Main Results:

Mucus plugs were present in 37% of the discovery set.
Differentially expressed genes were predominantly epithelial (e.g., decreased cilia maintenance, increased epithelial protection) and immune-related.
Epithelial gene expression patterns correlated with chronic bronchitis symptoms.
Immune gene expression varied with lung function and showed weaker association with mucus plugs compared to epithelial genes.
Key findings were validated in an independent cohort.

Conclusions:

Distinct gene expression patterns are associated with mucus plug presence, revealing critical biological pathways in mucus pathophysiology.
Variability in gene expression suggests a spectrum of mucus pathophysiology underlies mucus plugs and chronic bronchitis.
These findings provide a molecular basis for understanding mucus-related disorders in COPD.