Grant: Master's Award: Canada Graduate Scholarships

Summary (required) Allergic rhinitis (AR), or hayfever, is a coexisting condition in up to 80% of allergic asthma (AA) patients and can result in decreased performance at work and school, poor sleep quality, and impaired cognition. AR and AA occur due to inappropriate immune responses to a usually harmless substance (allergen). Respiratory tract cells release thymic stromal lymphopoietin (TSLP) in response to allergens. TSLP plays key roles in activating inflammatory pathways causing the release of chemicals that produce AR symptoms (sneezing, congestion, runny nose) and the classic narrowing of airways exhibited by AA patients. Patients with coexisting AR and AA experience greater asthma severity and healthcare usage than asthmatic patients without AR. Investigating therapies to treat both AR and AA would increase patient quality of life and relieve the burden imposed on the healthcare system. Tezepelumab (TZ) is a therapy approved to treat asthma that blocks TSLP. Elevated TSLP has been found in the noses and lungs of AR and AA patients, respectively; we hypothesize TZ will be effective in treating coexisting AR and AA. Fourteen participants will be given TZ for six months. Nasal allergen challenge (NAC) induces allergy symptoms and mimics natural allergen exposure via allergen extract administered directly into the nose. We will evaluate AR and AA symptoms following NAC, and measure TSLP and other allergic marker levels before and after TZ dosing to test efficacy in this population. We will also measure clinical markers of AR and AA compared to five nonallergic controls, which will add to our knowledge of the complex mechanisms of these diseases. Few studies have used NAC as a model of AA; our research is valuable in assessing safety and setting standards for future clinical trials.