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Date of Award

Fall 2012

Degree Type

Thesis

Degree Name

Master of Science (MSc)

Department

Health Sciences

Supervisor

Renee Labiris

Language

English

Abstract

Allergic asthma is a disease involving airway inflammation, commonly linked to allergen exposure. Computed tomography (CT) is used to quantitatively assess changes in density, hence inflammation, in the lung. CT imaging provides the ability to non-invasively and longitudinally study disease progression and evaluate treatment efficacy. The objective of this study was to determine the sensitivity of CT to detect the anti-inflammatory effects of budesonide (BUD) by measuring airway tissue density in a rat model of allergic airway disease.

Female Brown Norway rats were exposed intratracheally to house dust mite (HDM) extract (250 µg in 100µL saline) or saline control every other day for a total of five administrations (inflammatory phase). ABUD dose and temporal response study was performed usingBUD 0, 10, 100, and 300 µg/kg administered concurrently with HDM for three and six treatments (treatment phase). CT scanning was performed at baseline, post inflammatory phase, and after three and six BUD treatments. From the CT, density was measured in a defined volume of interest surrounding the major airways. Bronchoalveolar lavage (BAL) and histological samples were collected at the same time points.

After the inflammatory phase, a significant increase in peribronchial density was found in the HDM group compared to controls. This corresponded to a significant increase in inflammation by histology andBALtotal cell count (TCC), specifically eosinophils. Within the treatment phase after three treatments,BUD100 and 300 µg/kg led to a significant shift in lung density compared to HDM exposure alone, to a state similar to baseline. All BUD treated groups expressed a significant reduction in peribronchial density after six treatments. However, histology andBALTCC only showed a significant decrease in inflammation after six treatments for all three BUD doses.

CT densitometry is a sensitive, non-invasive method of evaluating the anti-inflammatory effects of budesonide and can be used for future screening of therapies in allergic lung models. Airway segmentation of CT permits the localized assessment of peribronchial inflammation, while other outcome measurements, such as BAL cytology, provide whole lung assessment which may not accurately reflect important regional changes.

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