This thesis investigates variability in airway caliber and the distribution of ventilation within the human lung as thought to occur in asthma. Currently, the understanding of how an integrated network of airways can lead to temporal and spatial variation as found in the human lung is unclear. Throughout this thesis, a multibranch airway tree model was used in a forward modeling approach.
In a variability study, the mean airway resistance (RL) was observed to be proportional to the standard deviation in airway resistance (SDRL) as reported in the literature under several conditions of airway diameter indicating the strong robustness of this behavior. The model predicted previously reported RL distributions and the reported proportionality of SDRL and RL, but only when we included coherency between airways.
In a second study, patient specific ventilation was investigated using an image functional approach by closing specific airways (creating defects) identified by hyperpolarized 3He MRI from asthmatic subjects. Impedance predictions from the imposed heterogeneous ventilation were then calculated and correlated to 3He MRI ventilation defect percent (VDP), plethysmography, and spirometry data. These predictions suggest the forced oscillation technique (FOT) to be a superior metric toward the evaluation of the VDP.
In a third study, we investigated how asymmetric branching could play a role in ventilation defect emergence and persistence. At high muscle activation levels simulating an asthmatic episode, airway trees with greater asymmetry reached steady state sooner, with defects that were more persistent in location, had lower RL values (~50%), and greater EL values (~25%) after bronchoconstriction. These results suggest the initial formation of ventilation defects was dependent on airway instability; however, the location and persistence of ventilation defects may be due to geometric airway structure.
By modeling the contribution of ventilation defects to lung impedance, we were able to show that defects can play a role in governing the relationship between RL and its variation, and the effect of defects through VDP could be better assessed using FOT. Moreover, lung structure contributed to the emergence and persistence of ventilation defects, meaning that defects could be potentially ameliorated through structural intervention.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:NSHD.ca#10222/36311 |
| Date | 13 August 2013 |
| Creators | Leary, Del |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
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