Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article


Master of Science


Medical Biophysics


Parraga, Grace

2nd Supervisor

Cunningham, Ian A.



Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic airflow obstruction, emphysematous destruction, and airway remodeling. Thoracic CT has previously revealed abnormalities in the small airways, where disease onset is believed to initiate. In previous COPD cohort studies, airway wall thinning and diminished total airway count (TAC) were observed with increasing disease severity. However, longitudinal insights are lacking. Accordingly, the objective of this thesis was to evaluate longitudinal CT airway measurements at baseline and after three-years in ex-smokers. I observed that CT TAC was decreased only in ex-smokers with COPD, whilst airway walls were thinner in both ex-smokers with and without COPD. To my knowledge, this is the first study to show TAC worsening over time in COPD, which suggests airway narrowing, obstruction, and/or obliteration. These longitudinal three-year findings in ex-smokers, in whom forced expiratory volume in 1-second did not change, provide insights into mechanisms of COPD progression.

Summary for Lay Audience

Chronic obstructive pulmonary disease (COPD) is a debilitating disease that worsens over time and results in symptoms such as chronic cough, difficulty breathing, wheezing, mucus production, and exercise limitation. It is most commonly caused by long-term exposure to tobacco cigarette smoke. COPD is believed to start in the small airways and then progress to other structures in the lungs. Breathing tests performed at the mouth are the current standard for clinical diagnosis and disease management. Unfortunately, these tests only provide global measurements of lung function, cannot inform on the unevenness of how inhaled air spreads throughout the lungs, and cannot capture changes and abnormalities in the small airways. Computed tomography (CT) imaging allows the visualization and evaluation of regional abnormalities in the lungs, including emphysema and airway structure. Importantly, airways on CT may reflect small airway abnormalities and provide additional information beyond what is offered with breathing tests. Previous research studies have shown that with increasing disease severity, the total number of airways on CT decreases and airway walls become thinner in patients with COPD. However, changes in these measurements over time are not well understood. Therefore, the objective of this thesis was to evaluate CT airway measurements in ex-smokers at their first visit and then again after three-years. In these participants, measurements of lung function evaluated with breathing tests did not change or worsen over this time period. I observed that the total number of airways was decreased after three-years only in ex-smokers with COPD, while airway walls were thinner in both ex-smokers with and without COPD. To my knowledge, this is the first study to show longitudinal worsening in the total number of CT-visible airways of patients with COPD. This finding may suggest that airways become thinned, blocked, and/or destroyed over time. Together, these results provide a better understanding of how airway structure changes over time in ex-smokers and patients with COPD. Furthermore, it demonstrates the benefit of using CT imaging to help researchers and clinicians to better evaluate and manage disease progression.

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.