Carli Monica Peters’ PhD Thesis Proposal

Title: “Relationship between airway anatomy and physiological function
Supervisor: Dr. William Sheel (Kinesiology)
Committee Members: Dr. Stephen Lam (Respiratory Medicine), Dr. Don McKenzie (Kinesiology), Dr Don Sin (Respiratory Medicine)

Background: Several studies have demonstrated that women have significantly smaller airways relative to lung size than men. Based on these anatomical differences, it cannot be assumed that the mechanical ventilatory response to exercise will be the same in men and women. Indeed, several studies have shown that women have a higher work of breathing (WOB) for a given minute ventilation than men. Given the strong influence airway radius has on determining resistance to flow, smaller airways in women compared to men likely contribute to the higher WOB observed. However, previous studies have an important limitation: they lack a direct link between airway anatomy measures and physiological function in the same subjects. The interrelationship between airway anatomy and function is such that small structural changes may have a profound influence on function. There is accumulating evidence that the hyperpnea and chlorine exposure associated with intense swim training can cause injury to the airway epithelium and lead to remodeling of the airway wall. While some studies investigating airway remodeling in athletes have included both men and women, a direct comparison between the sexes is lacking. Purpose: To characterize the impact of biological sex and chronic swim training on the relationship between airway anatomy and physiological function. Methods: Two groups of men and women will be recruited: 1) healthy young adults that are physically fit but don’t swim and 2) healthy young adults that swim competitively. Both groups will undergo two days of testing. The first day of testing will involve imaging of the airways and bronchial vasculature with a co-registered Autofluorescence-Optical Coherence Tomography probe as well as biomarker collection. The second day of testing will characterize the relationship between the WOB during high-intensity exercise and airway structure. Customized software will be created to quantify the size of the airway lumen, airway wall, and density of airway vasculature. Hypotheses: 1) Inherent sex-based differences in airway anatomy will explain the higher WOB in women compared to men during exercise. 2) Airway remodeling will be more severe (greater airway wall thickness, greater vascular density) in female compared to male swimmers. 3) Greater airway remodeling in female compared to male swimmers will exacerbate the sex-based differences in the mechanical ventilatory response to exercise. Significance: This study will provide novel insight into how inherent differences in airway anatomy between men and women affect respiratory mechanics. Insight will also be gained into whether high-level swim training causes airway remodeling that differs on the basis of biological sex.