Dissertation
Novel imaging tools to study mucociliary transport in health and disease
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2023
DOI: 10.25820/etd.006862
Abstract
The airway tree is a complex structure of branching tubes with a simple role of conducting air to the distal regions of the lungs for gas-exchange. With every breath, we inhale pathogenic particles and microbes. Yet, the lungs remain sterile due to several innate host defense mechanisms including mucociliary clearance (MCC) and mucociliary transport (MCT). Mucus secreted by epithelial cells traps particles and microbes and is transported out of the lungs by the action of cilia. Failure of this mechanism is implicated in the pathogenesis of many airway diseases including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). Understanding this key host defense mechanism is hindered by the lack of adequate and sensitive assays to measure mucus clearance along the airway tree. Using dynamic positron emission tomography (PET) scan and dynamic computed tomography (CT) scans, we developed a novel assay and novel analysis tools to measure mucus clearance in the small airways and determine the patterns of mucus transport in the large airways. We used newborn CF pigs as our disease model because porcine respiratory anatomy and physiology resemble humans and CF pigs recapitulate the hallmarks of CF lung disease in humans. We further characterized the normal pattern of mucus transport in large airways and found that in CF this pattern is disrupted. In addition, we demonstrated defective mucus clearance in the small airways of CF pigs. These findings contribute to better understanding of the role of defects in MCT in the pathogenesis of CF and other airways diseases. In addition, we developed novel methods and a framework of analysis tools that can be easily translated to humans and other airway diseases.
Details
- Title: Subtitle
- Novel imaging tools to study mucociliary transport in health and disease
- Creators
- Carley Stewart
- Contributors
- Mahmoud H Abou Alaiwa (Advisor)James A Ankrum (Committee Member)Joseph Zabner (Committee Member)Edward A Sander (Committee Member)Joseph M Reinhardt (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Biomedical Engineering
- Date degree season
- Summer 2023
- DOI
- 10.25820/etd.006862
- Publisher
- University of Iowa
- Number of pages
- x, 95 pages
- Copyright
- Copyright 2023 Carley Stewart
- Language
- English
- Date submitted
- 07/18/2023
- Description illustrations
- illustrations (some color)
- Description bibliographic
- Includes bibliographical references (pages 84-95.
- Public Abstract (ETD)
The airways’ main role in the body is to conduct air. With every breath, air brings in oxygen alongside other microparticles like dust, pollen, and bacteria. Therefore, to maintain a healthy environment the airways are equipped with defense mechanisms. One mechanism captures microparticles in a layer of mucus and transports it out of the lung through the beating action of tiny hair-like extensions called cilia. The mucus and the cilia work together to transport inhaled particles out of the airways. In some diseases, mucus can become too sticky, and this can result in this defense mechanism failing. The small airways, which reside deep in the lung, are often highly affected in disease states.
It is important to understand the details of how this mechanism fails, but current measurement methods are limited. Our group developed a new measurement method and novel analysis tools to close this knowledge gap. Using an imaging technique that utilizes a radioactive tracer and a detector to generate three-dimensional images, we studied mucus transport in a cystic fibrosis (CF) pig model. CF is a lung disease characterized by thick, sticky mucus. We found CF pigs to have abnormal transport in the small airways. We also further characterized transport in the large airways in normal and healthy pigs. Using novel analysis tools, we found new transport patterns and now are able to further describe how mucus moves in the large airways. These findings better understanding of mucus transport in healthy and diseased airways.
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center
- Record Identifier
- 9984454540802771
Metrics
1 File views/ downloads
29 Record Views