Research Project: Tezepelumab in the treatment of co-morbid allergic rhinitis and allergic asthma study (TEZARS) – An Open-Label Exploratory Mechanistic Pilot study to evaluate tezepelumab efficacy in asthma and allergic rhinitis

Allergic rhinitis (AR), commonly known as hay fever, affects up to 80% of people with asthma. Both conditions occur when the immune system overreacts to allergens such as pollen and dust mites. When allergens are inhaled, cells in the nose and lungs release TSLP, a protein that acts like an alarm, triggering immune responses that lead to inflammation. This inflammation causes symptoms including sneezing, nasal congestion, coughing, and wheezing.

Tezepelumab is a medication approved in Canada for the treatment of severe asthma that works by blocking TSLP. Many people with asthma also have AR and higher levels of TSLP in their noses, yet tezepelumab is not approved to treat both conditions due to limited research on its effects on nasal symptoms. We hypothesize tezepelumab will improve both asthma and AR by reducing upper and lower airway inflammation and symptoms.

In this study, 14 participants with both AR and asthma will receive tezepelumab for 12 months. A Nasal Allergen Challenge will be used to trigger an allergic response by applying allergen directly into the nose. Before treatment, and again after 6 and 12 months, we will evaluate nasal symptoms, measure TSLP and other inflammatory markers, assess lung function, and collect quality-of-life information.
This study addresses an important yet understudied patient population. Findings will improve our understanding of TSLP in AR and may support future clinical trials investigating tezepelumab as a treatment for both asthma and AR.

Research Project: Airway Neural Remodeling Drives iBALT Formation in Allergic Asthma.

Asthma affects millions of people worldwide, and many patients continue to experience symptoms that return even after the allergen that first triggered them is gone. This suggests the lungs retain a form of immune memory that keeps them primed to react to future exposures.

This project asks whether airway nerves help create that memory. In people with asthma, nerves in the lungs increase in number and change in structure after repeated allergen exposure. The goal is to determine whether these altered nerves promote the formation of small immune cell clusters, called inducible Bronchus-Associated Lymphoid Tissue (iBALT), that may act as sites keeping allergic inflammation active long after the initial trigger has cleared.

Using mouse models of asthma, three-dimensional imaging, and spatial gene analysis, this project will examine how nerves and immune cells interact during allergic inflammation. It will also test whether blocking specific nerve signals prevents iBALT from forming, which would help clarify whether nerve activity is required to sustain these immune cell clusters.

If successful, this work will identify a previously unrecognized connection between the nervous and immune systems in asthma. Clarifying how nerves contribute to persistent inflammation could point toward new treatment strategies for patients with severe asthma who do not respond well to existing medications, improving long-term disease control.

Research Project: Investigating Macrophage Paralysis and Neutrophilic Inflammation as Mechanisms of Asthma Exacerbation by Wildfire Smoke

Wildfires are becoming increasingly severe, and the smoke they produce is particularly harmful for people with asthma. However, how wildfire smoke exacerbates asthma is unclear. To answer this question, we will deliver wildfire smoke particles to mice and use special microscopes to observe their real-time effects on immune cells in the lung. We will first determine if wildfire smoke impairs macrophages—immune cells responsible for clearing any noxious substances we breath in. We will then test whether wildfire smoke increases neutrophils (inflammatory cells) in the lung, and whether this worsens asthma and makes it harder to treat. Ultimately, our findings could inform future treatment options for asthma exacerbated by wildfire smoke, and potentially other forms of treatment-resistant asthma.

Research Project: Defining a Non-Allergic Mast Cell-Mediated Neuroimmune Axis in Asthma

Asthma is an inflammatory airway disease that often causes symptoms such as coughing, wheezing, and shortness of breath. While asthma is classically considered an allergic disease, there are also non-allergic mechanisms that play a role. Mast cells and sensory neurons are two cell types found within the airways that can communicate with each other to promote airway inflammation. Mast cells express a surface protein that can detect molecules released by neurons and promote the onset of inflammation, and it has been shown that there is increased expression of this protein in asthmatic lung tissue. This project aims to understand the role of mast cell expressed surface proteins in the onset and maintenance of airway inflammation in asthma, independent of the traditional allergic context. Specifically, we will focus on how sensory neurons activate mast cells to promote the release of molecules that contribute to disease development. By increasing our understanding of how this receptor may promote asthma, this will allow us to potentially harness receptor inhibitors as a future therapeutic option for asthma patients.