Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma

Brendan K Huang; Brett M Elicker; Travis S Henry; Kimberly G Kallianos; Lewis D Hahn; Monica Tang; Franklin Heng; Charles E McCulloch; Nirav R Bhakta; Sharmila Majumdar; Jiwoong Choi; Loren C Denlinger; Sean B Fain; Annette T Hastie; Eric A Hoffman; Elliot Israel; Nizar N Jarjour; Bruce D Levy; Dave T Mauger; Kaharu Sumino; Sally E Wenzel; Mario Castro; Prescott G Woodruff; John V Fahy; NHLBI Severe Asthma Research Program

doi:10.1172/jci.insight.174124

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Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma

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Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma

Brendan K Huang, Brett M Elicker, Travis S Henry, Kimberly G Kallianos, Lewis D Hahn, Monica Tang, Franklin Heng, Charles E McCulloch, Nirav R Bhakta, Sharmila Majumdar, …

JCI Insight, Vol.9(3), e174124

02/08/2024

DOI: 10.1172/jci.insight.174124

PMCID: PMC10967478

PMID: 38127464

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Abstract

BACKGROUND Information about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow obstruction and to rationally design muco-active treatments. METHODS CT lung scans from 57 patients with asthma were analyzed to quantify mucus plug size and airway location, and paired CT scans obtained 3 years apart were analyzed to determine plug behavior over time. Radiologist annotations of mucus plugs were incorporated in an image-processing pipeline to generate size and location information that was related to measures of airflow. RESULTS The length distribution of 778 annotated mucus plugs was multimodal, and a 12 mm length defined short ("stubby", ≤12 mm) and long ("stringy", >12 mm) plug phenotypes. High mucus plug burden was disproportionately attributable to stringy mucus plugs. Mucus plugs localized predominantly to airway generations 6-9, and 47% of plugs in baseline scans persisted in the same airway for 3 years and fluctuated in length and volume. Mucus plugs in larger proximal generations had greater effects on spirometry measures than plugs in smaller distal generations, and a model of airflow that estimates the increased airway resistance attributable to plugs predicted a greater effect for proximal generations and more numerous mucus plugs. CONCLUSION Persistent mucus plugs in proximal airway generations occur in asthma and demonstrate a stochastic process of formation and resolution over time. Proximal airway mucus plugs are consequential for airflow and are in locations amenable to treatment by inhaled muco-active drugs or bronchoscopy. TRIAL REGISTRATION Clinicaltrials.gov; NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01716494, and NCT01760915.FUNDING AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and TEVA provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative.

Asthma

Biomedical and Clinical Sciences

Bronchoscopy

Clinical practice

Clinical Sciences

Diagnostic imaging

Health sciences

Humans

Lung

Mucus

Pulmonology

Rare Diseases

Respiratory

Tomography

X-Ray Computed

Details

Title: Subtitle: Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma
Creators: Brendan K Huang
Brett M Elicker
Travis S Henry
Kimberly G Kallianos
Lewis D Hahn
Monica Tang
Franklin Heng
Charles E McCulloch
Nirav R Bhakta
Sharmila Majumdar
Jiwoong Choi
Loren C Denlinger
Sean B Fain
Annette T Hastie
Eric A Hoffman
Elliot Israel
Nizar N Jarjour
Bruce D Levy
Dave T Mauger
Kaharu Sumino
Sally E Wenzel
Mario Castro
Prescott G Woodruff
John V Fahy
NHLBI Severe Asthma Research Program
Resource Type: Journal article
Publication Details: JCI Insight, Vol.9(3), e174124
DOI: 10.1172/jci.insight.174124
PMID: 38127464
PMCID: PMC10967478
NLM abbreviation: JCI Insight
ISSN: 2379-3708
Publisher: American Society for Clinical Investigation
Number of pages: e174124
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: T32 HL007185, F32 HL162422, R01 HL080414, UG1 HL139106, P01 HL107202, U01 HL146002, U10 HL109172, U10 HL109168, U10 HL109152, U10 HL109257, U10 HL109146, U10 HL109250, U10 HL109164, U10 109086; DOI: 10.13039/100004325, name: AstraZeneca, award: N/A; name: Boehringer-Ingelheim, award: N/A; DOI: 10.13039/100004328, name: Genentech, award: N/A; DOI: 10.13039/100004330, name: GlaxoSmithKline, award: N/A; name: Sanofi–Genzyme–Regeneron, award: N/A; DOI: 10.13039/100006259, name: TEVA, award: N/A
Language: English
Electronic publication date: 01/01/2024
Date published: 02/08/2024
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Iowa Neuroscience Institute; Health, Sport, and Human Physiology ; Mechanical Engineering; Internal Medicine
Record Identifier: 9984583732902771

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