Dr. Elizabeth Fixman
CIHR-ICRH/CAAIF PRIORITY ANNOUNCEMENT
ACUTE ASTHMA CARE ACROSS THE LIFESPAN
Sex-specific mechanisms by which environmental triggers promote durable changes to the lung to exacerbate type 2 innate and adaptive immunity
Asthma is a chronic inflammatory disease affecting >300 million people worldwide, and allergic asthma is the most common form. Although most asthmatics are reasonably well controlled by current therapies targeting the inflammatory response, more sophisticated therapies with the ability to reduce the development of asthma and disease exacerbations could impact millions. However, this requires a better understanding of the processes driving these destructive inflammatory responses. We have developed murine models to better understand what happens to the lung after exposure to allergens or respiratory viruses. We focus on two types of models: i) very young mice infected with respiratory syncytial virus (RSV), which in humans is associated with development of wheezing and asthma that can persist into adulthood; and ii) adult mice treated with an inflammatory mediator called IL-33, which in humans is implicated in asthma susceptibility as well as exacerbations. Our data provide evidence that following these exposures, the lung is durably changed, such that inflammation develops to normally innocuous stimuli. These changes are greater in females, in line with the observation that, in humans, more adult females than males have asthma. We have recently linked female sex hormones even in very young mice to these changes. Our goals are to better understand how early-life RSV infection induces long-term changes in the lung linked to asthma susceptibility; how sex hormones in very young mice influence the impact of early-life RSV infection on allergic responses in adults; and how IL-33 durably modifies the lung environment. Our findings will provide insight into mechanisms by which the lung is modified to promote allergic lung inflammation, more so in females, and why these responses are long-lasting. We are hopeful our models will provide information to guide development of novel therapeutic approaches to prevent or treat asthma in all children and all adults.
Dr. Eva Kaufmann
EARLY CAREER RESEARCHER AWARD IN ASTHMA
Trained Immunity in Eosinophils: Mechanisms and Therapeutic Opportunities
Familial hemophagocytic lymphohistiocytosis (fHLH) is a life-threatening dysregulation of the inflammatory response caused by genetic defects in the lymphocyte granule-mediated cytotoxic pathway. The only cure for this lethal disease is allogeneic hematopoietic stem cell transplantation (HSCT). The outcomes of HSCT for fHL can vary depending on several factors, including the specific genetic mutation, the control of HLH at the time of transplant, and the quality of the HSCT donor match. Our objective is to develop a gene therapy (GT) approach to treat patients affected by perforin-associated fHLH using systemic nanoparticle-mediated in vivo delivery of a prime editor specifically designed to correct the PRF1 gene, which encodes the perforin protein. We hypothesize that this approach will allow for the correction of PRF1 pathogenic variations directly within the HSC niche. This will enhance all aspects of the current cell therapy strategy targeting HSCs through precise gene correction, the avoidance of HSC collection, and myeloablative conditioning regimens.
This Award was jointly funded by CIHR-Institute of Circulatory and Respiratory Health (CIHR-ICRH), Canadian Allergy, Asthma and Immunology Foundation (CAAIF), Asthma Canada, and the Canadian Lung Association (CLA)
Dr. Christina Thornton
EARLY CAREER RESEARCHER AWARD IN ASTHMA
Evaluating the pyroaeromicrobiome of wildfire smoke and its role in asthma
Wildfire smoke is becoming a bigger health threat in Canada, especially for people with asthma. Most research has focused on the harmful chemicals and particles in smoke, but less is known about the microbes, such as bacteria and fungi, that smoke may also carry. Our research aims to study whether these smoke-borne microbes may worsen asthma attacks, especially harder-to-treat forms linked to neutrophilic inflammation. To do this, we will study this question in three parts. First, we will identify the living microbes present in wildfire smoke collected during controlled burns and real wildfire events in Canada. Second, we will use large population data from the UK Biobank to test whether wildfire smoke exposure is linked to asthma flare-ups, and whether a person’s microbiome may affect their risk. Third, we will study adults with asthma during wildfire season to see how real-world smoke exposure changes their airway and gut microbes, inflammation and symptoms. In this study, by combining environmental sampling, population health data and patient testing, we aim to provide new insight into how wildfire smoke affects asthma. The findings could help identify people at highest risk and support better prevention, monitoring and potentially treatment as wildfire seasons worsen.
This Award was jointly funded by CIHR-Institute of Circulatory and Respiratory Health (CIHR-ICRH), Canadian Allergy, Asthma and Immunology Foundation (CAAIF), Asthma Canada, and the Canadian Lung Association (CLA)
Dr. Connie Yang
ASTHMA CANADA-CAAIF RESEARCH GRANT IN
ASTHMA INNOVATION AND IMPACT
Severe Pediatric Asthma Remodeling and Key biomarkers (SPARK)
Asthma can cause long-term damage to the airways leading to low lung function. Some children develop low lung function that does not fully improve over time. Doctors currently have limited ways to determine why some children have ongoing low lung function.
This study will focus on children and adolescents with asthma who have low lung function. Using tests including CT scans, MRI scans, breathing tests, and tests of airway inflammation, we will investigate the underlying causes of reduced lung function and whether these changes improve after a short course of oral steroids. The study will include newer imaging and lung function tests that may be safer, more accessible, and easier to use in children.
By identifying test results linked to low lung function, this research aims to improve how children with asthma are evaluated and treated. The findings will help guide future studies and support more personalized approaches to asthma care.
Dr. Roma Sehmi
ASTHMA CANADA-CAAIF RESEARCH GRANT IN
ASTHMA INNOVATION AND IMPACT
Innate Lymphoid Cell—Autoimmunity Cross talk Driving Disease Burden in Severe Asthma
Asthma affects over 4.6 million Canadians. While recent biologic medications have improved outcomes for many, more than 50% of severe asthma sufferers continue to experience frequent attacks, persistent symptoms, and reduced quality of life. These patients carry most of the healthcare burden, yet the reasons their disease remains uncontrolled are not fully understood.
Our research focuses on two emerging drivers of severe, treatment-resistant asthma: group 2 innate lymphoid cells (ILC2s) and autoimmune reactions in the airways. ILC2s are potent inflammatory cells that release large amounts of asthma-related cytokines. In severe asthma, they become unusually active and resistant to steroids. At the same time, many patients develop autoantibodies which are immune proteins that mistakenly target the body’s own tissues. These autoantibodies are found in the airways of more than half of severe asthma patients and are linked to worse symptoms and poor response to biologics.
Recent findings from our team show that autoantibodies can trigger inflammatory signals, including a protein factor called Tumour necrosis factor like peptide 1A (TL1A), which activate ILC2s and can push them towards a harmful, steroid-resistant state. This cycle may drive persistent inflammation and repeated attacks. Our study will dissect this interaction in patient airway samples and laboratory models to identify new treatment targets, including TL1A, with the goal of improving therapies for severe asthma.
Dr. Adil Adati
CAAIF-CASP RESEARCH GRANT IN
HEREDITARY ANGIOEDEMA (HAE)
Diagnostic Accuracy of Specific Plasma Kallikrein Activity and High-Molecular-Weight Kininogen Cleavage for Identifying Hereditary Angioedema of Unknown Cause
Hereditary angioedema of unknown cause (HAE-UNK) is characterized by recurrent angioedema without wheals in the absence of C1 inhibitor deficiency or a known pathogenic variant associated with hereditary angioedema (HAE). Unlike HAE due to C1 inhibitor deficiency or known genetic variants (e.g., PLG, FXII), HAE-UNK lacks validated diagnostic biomarkers. A key challenge in clinical practice is distinguishing mast cell-mediated angioedema (MCMA) from HAE-UNK, which remains a diagnosis of exclusion. Differentiation from MCMA often relies on prolonged therapeutic trials of high-dose antihistamines and omalizumab, delaying diagnosis and access to effective targeted therapies. This cross-sectional diagnostic accuracy study aims to evaluate whether specific plasma kallikrein (sPKa) activity and high-molecular-weight kininogen (HMWK) cleavage can serve as clinically useful biomarkers for identifying HAE-UNK. Participants will undergo blood collection and clinical data capture. sPKa activity will be measured using a published chromogenic amidolytic assay following cold plasma incubation, while HMWK cleavage will be quantified as a marker of contact system activation. The primary outcome is the area under the receiver operating characteristic curve (ROC AUC) for distinguishing HAE-UNK from MCMA using sPKa activity, HMWK cleavage, and a combined biomarker model. Findings will inform future multicenter validation studies and development of biomarker-guided diagnostic strategies for HAE-UNK.
TBA
CAAIF FOOD ALLERGY CLINICAL RESEARCH GRANT
TBA
Dr. Modjeh Matloubi
CAAIF-CLA RESEARCH FELLOWSHIP IN ASTHMA
Mechanisms for Oxidized Phosphatidylcholine-Mediated Glucocorticoid Insensitivity in Allergic Asthma
Asthma is one of the most common long-term diseases affecting children and a leading cause of emergency healthcare visits in Canada, especially among preschool-aged children. A fundamental feature of asthma is persistent inflammation in the lung, which predisposes patients to frequent asthma attacks and poor quality of life. Although inhaled glucocorticoids (steroids) are the main treatment for controlling lung inflammation, in many children they are ineffective, so asthma symptoms are frequent and severe. As a result, patients may often require higher doses of steroids, which increases the risk of negative side effects. Understanding why some children respond poorly to steroid treatment is essential for improving their asthma care.
This project investigates how oxidative stress, a harmful process that occurs alongside inflammation in the lung, contributes to ineffective steroid treatment. Specifically, we are studying oxidized fat-like molecules called OxPCs (oxidized phosphatidylcholines) that are generated by oxidative stress in the lungs. Using human lung cells and tissues and experimental models of asthma we will determine how OxPCs reduce the effectiveness of steroid treatment and whether blocking their effects can restore the benefits of existing therapies. We will also perform the first screen of blood samples from preschool-aged children with asthma to determine whether biomarkers for oxidative stress in the lungs can predict how well a patient responds to steroid therapy.
This fellowship was jointly funded by the Canadian Allergy, Asthma and Immunology Foundation (CAAIF) and the Canadian Lung Association (CLA).
Dr. Brock Williams
CAAIF-CLA ALLIED HEALTH OPERATING GRANT
Dietary Intake and Micronutrient Status in Children with Asthma and Comorbid Food Allergy
Asthma is one of the most common chronic diseases in children and can make breathing difficult by causing swelling and narrowing of the airways. Many children with asthma also have food allergies, requiring them to avoid foods that are important sources of vitamins and minerals. This may make it harder to get enough of the nutrients needed for growth, immune function, and lung health. This study will recruit 100 children aged 6 to 18 years with both asthma and food allergies. Participants will complete an online questionnaire about the foods they usually eat, and blood samples will be collected to measure important nutrients, including iron, vitamin A, selenium, and zinc. By comparing what children eat with the nutrient levels in their blood, we will identify which nutrients children with asthma and food allergies may not be getting enough of. We will also examine whether certain eating patterns are associated with poorer asthma control.
The findings will help identify children who may be at risk of nutrient deficiencies and provide evidence to support practical nutrition screening and dietary guidance for families and healthcare providers. Ultimately, this research aims to improve the nutritional care and long-term health of children living with asthma and food allergies.
This grant was jointly funded by the Canadian Allergy, Asthma and Immunology Foundation (CAAIF) and the Canadian Lung Association (CLA).
Nadia Suray Tan
CAAIF GRADUATE STUDENT RESEARCH GRANT IN ASTHMA SUPPORTED BY ASTRAZENECA CANADA
Exacerbation-Associated Lymphopenia Drives Autoreactive B Cell Expansion and Airway Autoimmunity in Asthma
Asthma affects millions of people, yet many continue to experience severe symptoms and frequent flare-ups despite receiving the best available treatments. Our research suggests that, in some individuals, asthma may involve an autoimmune process in which the immune system mistakenly targets the airways.
This project will investigate the role of B cells, immune cells that normally protect us from infection. In severe asthma, these cells may become dysregulated and produce harmful antibodies that contribute to persistent inflammation and airway damage. By studying paired blood and airway samples from people with asthma, we aim to understand what triggers these abnormal immune responses, particularly during flare-ups, and why they persist despite treatment.
Ultimately, this research could identify biomarkers to detect patients with autoimmune features of asthma and reveal new therapeutic targets. This may help move asthma care toward more personalized treatments that address the underlying cause of disease and improve outcomes for patients who currently have limited treatment options.
Abigail Davis
GRADUATE STUDENT AWARDS IN ASTHMA
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.
This Award was jointly funded by Asthma Canada and CAAIF.
Shuqi Cai
GRADUATE STUDENT AWARDS IN ASTHMA
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.
This Award was jointly funded by CAAIF and Asthma Canada.
Max Housefather
CAAIF GRADUATE STUDENT AWARDS IN ASTHMA
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.
This Award was jointly funded by CAAIF and Asthma Canada.
Austin Pozniak
GRADUATE STUDENT AWARDS IN ASTHMA
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.
This Award was jointly funded by Asthma Canada and CAAIF.