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Title: Studying the effect of cigarette smoke exposure on murine models of allergic asthma
Author: Dale, Nicole
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Exposure to pollution and active or passive smoking have been associated with a worsened asthma severity and a reduced response to treatment. These poorly controlled asthmatics are responsible for the majority of the economic burden of the disease but how pollution and/or cigarette smoke (CS) impacts on the disease is not well understood. The aim of this thesis was to develop a murine model of allergic asthma where CS exposure results in a change in model phenotype and the sensitivity of the response to pharmacological intervention. Two preclinical models of allergic asthma were utilised: the ovalbumin (OVA) model which had previously been established in-house, and the house dust mite (HDM) model which I developed in this thesis. As topical HDM exposure is known to cause innate inflammation I developed an allergic model where HDM challenge resulted in inflammation only in the mice which had been previously sensitised to HDM. The allergic inflammation in this model was accompanied by allergic airway hyper responsiveness, however the LAR was not observed in this model. CS exposure did not have a dramatic impact on the cellular inflammation in either the OVA- or the HDM-driven model, nor did it impact upon the anti-inflammatory effects of oral steroid treatment with the exception of the addition of a steroid-insensitive neutrophil population. However CS exposure attenuated the AHR observed in the OVA and the HDM models. Finally cigarette smoke exposure not only enhanced the OVA-induced LAR but also rendered this response completely insensitive to oral steroid treatment. Further investigation into the effects of CS in these two models may provide clues as to the mechanisms behind the effect of smoking on asthma in the clinic. The CS-enhanced LAR model could be invaluable in understanding the clinical phenotype of treatment resistance in smoking asthmatics.
Supervisor: Birrell, Mark A. ; Belvisi, Maria G. Sponsor: Medical Research Council ; GlaxoSmithKline
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available