Optimizing The Nasal Allergen Challenge Model For The Study Of Allergic Rhinitis

dc.contributor.authorSoliman, Menaen
dc.contributor.departmentBiomedical and Molecular Sciencesen
dc.contributor.supervisorEllis, Anne K.en
dc.date2015-09-30 16:18:30.051
dc.degree.grantorQueen's University at Kingstonen
dc.descriptionThesis (Master, Biomedical & Molecular Sciences) -- Queen's University, 2015-09-30 16:18:30.051en
dc.description.abstractBackground The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC) uses a Nasal Allergen Challenge (NAC) model to study the pathophysiology of AR and provides proof of concept for novel therapeutics. The NAC model needs to ensure optimal participant qualification, allergen challenge, clinical symptoms capture and biological samples collection. Repeatability of the protocol is key to ensuring unbiased efficacy analysis of novel therapeutics. The effect of allergen challenge on IL-33 gene expression and its relation to IL1RL1 receptor and cytokine secretion was investigated. Methods Several iterations of the NAC protocol was tested, comparing variations of qualifying criteria based on the Total Nasal Symptom Score (TNSS) and Peak Nasal Inspiratory Flow (PNIF). The lowest allergen concentration was delivered and TNSS and PNIF recorded 15 minutes later. Participants qualified if the particular criteria for the protocol were met, otherwise the next higher allergen concentration (4-fold increase), was administered until the targets were reached. Participants returned for a NAC visit and received varying allergen challenge concentrations depending on the protocol, TNSS/PNIF were recorded at 15 minutes, 30 minutes, 1 hour, and hourly up to 12 hours, a 24 hour time point was added in later iterations. Repeatability was evaluated using a 3-4week interval between screening, NAC1, and NAC2 visits. Various biomarker samples were collected. Results A combined TNSS and PNIF criterion was more successful in qualifying participants. The cumulative allergen challenge (CAC) protocol proved more reliable in producing a robust clinical and biomarker response. Repeatability of the CAC protocol was achieved with a 3-week interval between visits, on a clinical and biological basis. IL-33 cytokine is an important biomarker in initiating the inflammatory response in AR in humans. IL-33 and IL1RL1 expression might employ a negative feedback mechanism in human nasal epithelial cells. Comparing the clinical and biological response to ragweed vs cat allergen challenge, proved the CAC protocol’s suitability for use employing different allergens. Conclusion The AR-CIC’s CAC protocol is an effective method of studying AR, capable of generating measurable and repeatable clinical and biomarker responses, enabling better understanding of AR pathophysiology and ensuring that any change would be purely due to medication under investigation in a clinical trial setting.en
dc.description.restricted-thesisThis thesis contains data that is currently being prepared for publication. I have discussed this option with my supervisor Dr. Anne Ellis and she agrees to place a restriction on the thesis until the manuscripts have been accepted and published. Thank you for your help.en
dc.relation.ispartofseriesCanadian thesesen
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dc.subjectAllergic Rhinitis - Clinical Investigator Collaborativeen
dc.subjectAllergic Rhinitisen
dc.subjectClinical Trail Designen
dc.subjectNasal Allergen Challengeen
dc.titleOptimizing The Nasal Allergen Challenge Model For The Study Of Allergic Rhinitisen
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