Award Partner: Canadian Consortium of Clinical Trial Training Platform (CANTRAIN)

Effects of budesonide on responses to diesel exhaust and allergen exposures in allergic rhinitis

About one in every four Canadians suffers from a disease called allergic rhinitis. This causes symptoms like sneezing, itching, watery eyes, and difficulty breathing, especially when people inhale allergens from sources like trees and grasses. A type of medicine called nasal corticosteroids can usually help reduce these symptoms.
However, we do not know how exposure to air pollution, such as diesel exhaust, which is common in cities and industrial areas, might make this disease worse. We also do not know if nasal corticosteroids can help reduce the effects of exposure to diesel exhaust.

 

To investigate this, we conducted a study where we exposed people with allergic rhinitis to allergens and diesel exhaust separately, both with and without the use of nasal corticosteroids. This study was conducted at the Air Pollution Exposure Laboratory (APEL), a leading research facility that uses advanced controlled exposure methods to study how air pollution affects human health.

 

I will be looking at changes in how the nose functions as well as the levels of cells and small proteins in the nose that can underly symptoms, to see if nasal corticosteroids can effectively treat the effects of exposure to allergens and diesel exhaust.

 

The Master’s Studentship 2023 Award, supported by the Canadian Consortium of Clinical Trial Training Platform (CANTRAIN) Clinical Trials Training Program and Michael Smith Health Research BC, will thus help us evaluate a low-cost, accessible treatment for this growing health concern. This work will be supported by the Legacy for Airway Health (LAH), which supports knowledge translation and allows us to consult directly with patients. Since this work is being done in British Columbia, it also helps build local expertise in respiratory clinical trials and research.

End of Award Update – December 2024

 

Results

Allergens and air pollution can trigger inflammation in the nose, leading to irritation and discomfort for many people. We discovered that budesonide, a medicine often used to treat nasal allergies, can reduce levels of an important inflammation-causing protein (IL-5) in the nose. Budesonide works well even after exposure to diesel exhaust (DE), a major component of traffic related air pollution (TRAP). We also found that exposure to allergen and DE can lead to temporary changes to the DNA of nasal cells, which may affect how they function. These changes are what we call epigenetic changes, as they do not change the DNA sequence, just what is stuck on it. Interestingly, we found that budesonide may reverse these changes caused by allergens. These results are exciting because they show that budesonide can likely help people with nasal allergies breathe more easily, even if they are exposed to allergens or traffic pollution, which are very common.  

 

Impact

We have presented our findings at major national and international venues, such as the American Thoracic Society (ATS) 2024 International Conference, and are working on submitting them to a leading health research journal for publication. This will help doctors and other healthcare professionals learn about how this common medicine has new beneficial effects so that they can better treat patients during allergy season or periods of higher air pollution.  

 

Potential Influence

Our findings will allow us to get a better understanding of how medicines like budesonide interact with things we breathe in, like allergens and traffic pollution, on multiple levels. Other scientists can use our results to help them in making new medicines, as well as to research new health benefits for existing medicines. Scientists and doctors can also use our results to help improve guidelines so that patients can make better use of medicines like budesonide to reduce the impact of their nasal allergies. In addition to helping patients live better lives, this will reduce missed work due to symptoms, reducing costs to the Canadian and international economy. Leading this study has also allowed me to gain valuable skills for performing independent clinical research as part of a diverse, interdisciplinary team. This will allow me to continue to contribute to future clinical trials and health research in Canada so that we can tackle current and emerging health challenges, like the COVID-19 pandemic. 

 

Next Steps

We are in the process of finalizing and submitting a manuscript containing our research findings to a leading health research journal so other scientists and healthcare professionals can learn about this work. We are also collaborating with our highly capable knowledge mobilization unit, the Legacy for Airway Health (https://www.legacyairwayhealth.ca/), to get the word out throughout the wider community, based on dialogue with patient partners and additional outreach efforts. 

 

Useful Links

Addressing equity in clinical trials: development of a rural clinical trials research program

Clinical trials are essential for the development and optimization of medical therapies. However, clinical trial access is limited in rural and small communities in Canada. This is an important health equity issue as rural populations often to not have the opportunity to access investigational therapies and clinical trial results often do not reflect the health of rural populations. This project, which is funded by the CANTRAIN Clinical Trials Training Program, Michael Smith Health Research BC, the Accelerating Clinical Trials Consortium and the Canadian Institutes for Health Research. This project aims to build a rural clinical trials program in the East Kootenay region of British Columbia. It will build develop partnerships among educational institutions, Interior Health and community organizations. A community advisory board will be developed to seek community input into the program development and clinical trial selection. The principal investigator is Dr. Denise Jaworsky who is a rural general internal medicine specialist, but this project is a collaboration among a team of researchers from Interior Health, UBC and College of the Rockies. This project aims to improve clinical trial access for populations in the East Kootenay region and develop models and best practices to support rural clinical trial access in other rural communities in Canada.

SIMPLIFY-SABR-COMET

This project is an international randomized clinical trial being implemented across 12 Canadian and 5 International centers exploring the effectiveness of Stereotactic Ablative Radiotherapy (SABR) in the treatment of oligometastatic cancer. SABR is a modern radiotherapy technique for cancer treatment that delivers high doses of radiation to small tumor targets, while trying to avoid healthy tissues and organs. However, SABR treatment requires increased planning, treatment time, cost and potential for higher toxicity due to the higher dose and avoidance of nearby normal tissue. The purpose of this study is to compare different doses of SABR regarding toxicity, progression-free survival, quality of life, and cost-effectiveness.  

Along with funding from The CANadian Consortium of Clinical Trial TRAINing platform (CANTRAIN), The Michael Smith Health Research BC (Health Research BC) will be providing funding as part of the 2023-2024 CANTRAIN Doctoral Studentship to help develop the project in British Columbia. 

Our research team is based in Northern BC in Prince George at BC Cancer – Prince George with a focus on radiotherapy research and large-scale clinical trials. This project is based on previous research from our lab, and it is being developed to build on our previous findings.  

The outcomes of this project will contribute valuable insights to shape cancer treatment approaches, policies, and decision-making processes, considering their impact on healthcare resources and the burden on patients. 

Enhancing Early Relapse Detection in Testicular Cancer through Rolling Circle Amplification of microRNA Biomarkers

This project aims to improve the accuracy of early-stage testicular germ cell tumor (GCT) relapse detection in patients through rolling circle amplification (RCA) of plasma microRNA miR371. GCTs pose a significant challenge in clinical management due to the lack of sensitive and specific biomarkers for early relapse detection. Patients are at risk of over-treatment and long-term chemotherapy toxicity that negatively impacts life expectancy and quality of life. Patient blood samples from the BC provincial genitourinary biobank will be used.

 

Commonly used Polymerase Chain Reaction (PCR)-based detection methods have limitations such as precise temperature control requirements that other isothermal amplification techniques lack. RCA is an isothermal method that is effective in treatment and research applications. The clinical validity of microRNA miR371a-3p has been shown to be a potential biomarker for non-teratoma GCTs. However, the sensitivity of this biomarker in early-stage GCT detection using current PCR methods is low, and more accurate methods to detect smaller amounts of circulating miR371 are needed. RCA result sensitivity will be evaluated against PCR results.

 

The successful implementation of RCA will validate a more sensitive method for miR371 analysis. This will enhance clinical decision-making, reduce treatment toxicity, and extend the reach and applicability of early GCT relapse detection to resource-limited settings.
Andy Jia is a Master of Science student specializing in Interdisciplinary Oncology at the University of British Columbia (UBC). The project will be conducted in the Nappi Lab at the Vancouver Prostate Centre, which has extensive experience in miR371 analysis.

 

The Canadian Consortium of Clinical Trial Training Platform (CANTRAIN) and Michael Smith Health Research BC provide funding through the CANTRAIN-CTTP & Michael Smith Health Research BC Master’s Studentship 2023 Award Program.

End of Award Update – December 2024

 

Results

Our promising preliminary results demonstrated that the RCA method can successfully amplify and detect miR371 samples. Our findings indicate that synthetic miR371 was amplified to significant concentrations, and optimizations to our probe designs improved our results with each modification.

 

Impact

The project relies on plasma samples from patients enrolled in the provincial Genitourinary Cancers (GU) biobank that have already been collected and analyzed. Hence, the findings of this project can profoundly impact the clinical management of testicular cancer. RCA can be easily implemented in resource-limited settings, including rural areas and developing countries, extending its reach and applicability beyond the laboratory setting.

 

Potential Influence

The impact of this research project is expected to be significant. The primary expected result is validating a new sensitive method for miR371 analysis that could predict tumor relapse in patients with clinical stage 1 testicular germ cell tumors. This validation will enhance clinical decision-making, improve patient management, and reduce unnecessary treatments, leading to reduced healthcare expenses in British Columbia.

 

Next Steps

Continued optimization of the RCA protocol will be implemented. Patient samples will be used extensively, and to reach a lower temperature of RCA incubation and ensure accurate detection, new probes will be designed, and different reagents will be tested. RCA implementation with electrochemical biosensors for point-of-care detection will be investigated in depth when a lower temperature of RCA amplification has been successfully reached.

 

Useful Links

  • To learn more about the overarching miR371 project: https://clinicaltrials.gov/study/NCT04435756
  • The Nappi Lab website: https://nappilab.med.ubc.ca/