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Awan-Thesis-Fall20253.09 MB
Embargoed Access, Embargo ends: 01/23/2028
Dissertation
Structural lung pathologies capture systemic inflammation, mortality, and impaired lung function in COPD
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2025
DOI: 10.25820/etd.008193
Abstract
Computed tomography (CT) texture analysis offers a sensitive and quantitative approach to monitor chronic obstructive pulmonary disease (COPD) progression by capturing subtle yet specific structural alterations in the lung that go beyond conventional imaging metrics, such as emphysema and air trapping. In particular, bronchovascular bundle (BVB) texture, which encompasses both the airway walls and surrounding vasculature, together with the CT density gradient (CTDG) texture, which quantifies the parenchymal texture surrounding these bundles, provides a complementary view of peribronchial structural remodeling and inflammatory processes considered central hallmarks of COPD. Importantly, both BVB abnormalities and CTDG are independently associated with respiratory morbidity and all-cause mortality, even after accounting for traditional imaging biomarkers such as CT derived emphysema and Pi10 (the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm), highlighting their additive prognostic value.
At a mechanistic level, variations in BVB and CTDG textures correspond to molecular signatures associated with extracellular matrix remodeling, inflammation, and tissue stiffening, linking peribronchial imaging phenotypes with biologically meaningful processes underlying COPD pathogenesis. Notably, CTDG demonstrates the ability to detect early subclinical disease by capturing structural and molecular changes before overt functional impairment becomes evident. Furthermore, CTDG can track longitudinal structural progression in individuals with preserved ratio impaired spirometry (PRISm), providing a dynamic measure of disease evolution and a sensitive biomarker for risk stratification.
These structural pathologies translate directly into functional impairment localized to the BVB region. Increased CTDG reflects elevated tissue stiffness, which in turn leads to measurable declines in regional airflow and gas exchange. By integrating BVB morphology with CTDG based peribronchial texture assessment, we establish a direct link between structural remodeling and its functional consequences, offering a comprehensive framework for understanding disease biology and monitoring progression.
Overall, CT texture metrics, particularly CTDG surrounding BVB, offer an integrated perspective on COPD pathophysiology, bridging structural, molecular, and functional dimensions. These measures enhance early detection, improve prognostic precision, and provide mechanistic insights into chronic respiratory disease progression, paving the way for personalized monitoring and potential therapeutic targeting of early peribronchial remodeling.
Details
- Title: Subtitle
- Structural lung pathologies capture systemic inflammation, mortality, and impaired lung function in COPD
- Creators
- Hira Anees Awan
- Contributors
- Joseph M Reinhardt (Advisor)Eric A Hoffman (Committee Member)Alejandro P Comellas (Committee Member)Edward A. Sander (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Biomedical Engineering
- Date degree season
- Autumn 2025
- DOI
- 10.25820/etd.008193
- Publisher
- University of Iowa
- Number of pages
- xvii, 153 pages
- Copyright
- Copyright 2025 Hira Anees Awan
- Comment
- This thesis has been optimized for improved web viewing. If you require the original version, contact the University Archives at the University of Iowa: https://www.lib.uiowa.edu/sc/contact/
- Language
- English
- Date submitted
- 11/21/2025
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 91-113).
- Public Abstract (ETD)
- Computed tomography (CT) scans can reveal subtle changes in the lungs that help track the progression of chronic obstructive pulmonary disease (COPD). By looking at the structure of bronchovascular bundles (BVBs), which include the airways and blood vessels in the lungs, and the surrounding tissue using a measure called the CT density gradient (CTDG), researchers can detect early signs of lung remodeling and inflammation that traditional imaging methods may miss. Both BVB and CTDG changes are linked to worse lung health and higher risk of death, even when standard measures of lung damage are taken into account.
These imaging features also correspond to underlying biological changes in the lungs, including tissue stiffening and inflammation, which are central to the development of COPD. CTDG is particularly useful for capturing early disease before people notice breathing problems and can track how lung structure changes over time in people with mild or early stage COPD, helping identify those at higher risk for progression.
Changes in the structure of BVBs are closely tied to how well the lungs work. Stiffer tissue, as detected by higher CTDG, can reduce airflow and gas exchange in specific lung regions. By combining information about BVB structure and CTDG, researchers can connect structural changes in the lungs with their impact on breathing, providing a more complete picture of disease progression.
Overall, these CT based measures give a detailed view of COPD by linking changes in lung structure, tissue biology, and function. They offer a powerful tool for early detection, monitoring disease progression, and guiding treatments aimed at preventing or slowing lung damage.
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering
- Record Identifier
- 9985135345402771
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