ß÷ßäÉçÇø

Joshua Bentley

Project title: Pulmonary hypertension due to interstitial lung disease

Supervisor: Dr. Rhea Varughese

(Studentship sponsored by Jamie Fleming Summer Studentship Award)

Please provide a short abstract of your project funded by the ATI summer studentship.
Patients with interstitial lung disease (ILD) often develop pulmonary hypertension (PH). The INCREASE trial demonstrated that inhaled treprostinil can improve 6 minute walk distances for these patients. Our objective was to determine whether lung transplant recipients that had pre-existing ILD and PH would have benefited from inhaled treprostinil. Patients that met the INCREASE trial eligibility criteria had lower diffusion capacities, higher 6 minute walk distances, and less pre-transplant prednisone usage than those who were ineligible. There was no difference in post-transplant survival between groups. Only a small portion of lung transplant recipients would have been eligible for pre-transplant inhaled treprostinil.

How has the support from the ß÷ßäÉçÇø Transplant Institute aided your success in conducting research?
Thanks to the ATI, I was able to step into health research immediately after graduating with my Bachelor of Science in Kinesiology. I appreciate having had the opportunity to learn more about health research and apply some of the skills and knowledge obtained from my degree program as I look toward further medical education.

How would you describe your research project in plain language for a general audience?
Lung transplantation is a life saving procedure for many people, including those with high blood pressure in the lungs due to a disease called interstitial lung disease. Treprostinil is a drug that may reduce blood pressure in the lungs and thereby improve the lives of these patients, especially while they are waiting for a transplant. We looked into the data of a number of patients who received lung transplants and found that only a small portion of these patients would have been eligible to receive treprostinil pre-transplant. Further investigation is required to evaluate how this drug may be used to help people awaiting lung transplant.

Ivan Ma

Project title: The Use of Ice Recrystallization Inhibitors (IRIs) and Ex Vivo Lung Perfusion to Facilitate Lung Cryopreservation

Supervisor: Dr. Jason Acker

(Studentship sponsored by Jamie Fleming Summer Studentship Award)

Please provide a short abstract of your project funded by the ATI summer studentship.
Cryopreservation is suggested as one possible solution to drastically increase the preservation time of donor organs for transplantation. However, ice crystal growth during freeze-thaw causes irreparable damage to the cells. Therefore, ice recrystallization inhibitors (IRIs) can potentially be used to control ice growth during thawing to reduce freezing-induced damage. The lungs of Sprague Dawley rats are procured and then perfused on a perfusion apparatus for four hours. Lung compliance and vascular resistance will be monitored to evaluate lung health. The objective is to assess any possible toxicity effects and the ability of IRIs to control ice growth in lung tissue.

How has the support from the ß÷ßäÉçÇø Transplant Institute aided your success in conducting research?
I am extremely grateful for the ß÷ßäÉçÇø Transplant Institute (ATI) as I have been given the opportunity to lead my own research project and develop my skills as a researcher. The funding provided by ATI has allowed me to fully dedicate my time to this project. I have improved my practical skills involved with performing animal surgery and running organ perfusion experiments. In addition, I have learned various skills involved with running different assays and interpreting those results. My understanding of lung physiology has greatly improved and I feel much more confident in my skills as a researcher. All the experience that I have gained from this project is invaluable to me as I look to begin my Masters degree in the same department this Fall.

How would you describe your research project in plain language for a general audience?
One of the main issues faced with organ transplantations is that there are more organs needed than there are available for safe transplantation. The limited storage time of these donor organs contributes to the shortage of organs available for transplantation. Currently organs are stored in ice coolers for a few hours or attached to perfusion machines for a maximum of 12 to 24 hours. Below-zero degree storage (cryopreservation) of organs may extend storage time and help alleviate shortages of donor organs. However, an issue faced with organ preservation is ice growth both in and around the cells of the tissue as it causes irreparable damage. Although there are methods of cryopreserving organs without ice formation, those methods face issues of their own. Several species of cold-adapted animals can survive while “partially frozen” during the winter by generating special molecules to decrease their freezing temperature and control ice formation inside their cells. For example, wood frogs can survive temperatures as low as -20°C. Thus, the control of ice growth is being investigated as a viable solution for improved organ preservation. Ice recrystallization inhibitors (IRIs) are small molecules that are capable of preventing existing ice crystals from getting larger especially during thawing of frozen organs. Our experiment will use a novel system to perfuse rat lungs ex-situ (outside the body) with different concentrations of IRIs. The goal of this project is to establish ideal perfusion conditions, assess IRI function and minimize any potential toxic effects. The results of the work can help pave the way for an optimized cryopreservation protocol of donor lungs through identifying the safe concentrations of IRI that can be used and the best method of delivery. Additionally, similar protocols can be adapted to cryopreserve other organs such as kidneys, livers and hearts.

Stefan Lordache

Project title: Characterization of Patients with Pulmonary Arterial Hypertension in ß÷ßäÉçÇø

(Studentship sponsored by Jamie Fleming Summer Studentship Award)

Supervisor: Dr. Rhea Varughese

Please provide a short abstract of your project funded by ATI summer studentship.
My project analyzes ß÷ßäÉçÇøn pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients while contributing to the Canadian Pulmonary Hypertension Registry (CPHR). This study looks at consenting adult PAH and CTEPH patients that are followed by the pulmonary hypertension (PH) clinics in Edmonton and Calgary. Data is collected from electronic health records and paper charts. Descriptive statistics and survival analysis will be performed to understand this patient population. We expect to understand the demographics of PAH and CTEPH patients in ß÷ßäÉçÇø, what medications they use for their lung disease, how many are referred for lung transplantation, and their mortality. We anticipate that our results will be similar to Canadian and international data. This information will be used to understand the needs of ß÷ßäÉçÇøn PH patients, leading to quality improvement and future research.

How has the support from the ß÷ßäÉçÇø Transplant Institute helped you succeed in your research?
The ß÷ßäÉçÇø Transplant Institute (ATI) has provided generous support for the enhancement of my research. I am very grateful for the funding provided by the ß÷ßäÉçÇø Transplant Institute, whose generosity and kindness has served as encouragement for my efforts as a student in the Faculty of Science, as well as excelling in my research throughout the summer. Through their support they have lightened my financial burden, allowing me to focus on research and get the most out of my student experience at the ß÷ßäÉçÇø. I am able to develop as a person and obtain experience in research. With the ATI’s support I can focus solely on my studies, allowing me the wonderful opportunity of performing research all summer, which helps other people and broadens my knowledge and understanding of different concepts. It is very rewarding to grow personally, to have a new understanding of myself and ultimately be able to help others through my work. By being able to perform research I have the opportunity to connect with other faculty and student researchers, get hands-on experience in the research field and learn valuable skills: professionalism, time management, multi-tasking, online research tools. Through this project I have gained a deeper understanding of the scientific process, developed research questions, formed, and tested hypotheses, learned to productively communicate my ideas, and reported findings. Ultimately this project allows me to pursue my interests in the medical field, learn something new, sharpen my problem-solving skills and will challenge myself in new ways. Thank you ATI for your support, and for providing me with the opportunity to achieve beyond my expectations.

How would you describe your research project in plain language for a public audience?
My research project is about pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). These are rare diseases that affect the pulmonary arteries and arterioles, leading to shortness of breath, functional limitation, right heart failure, and eventual death. As the prevalence of PAH is 22 cases per 100000 individuals and CTEPH is 12 cases per 100000 individuals, characterizing these diseases is challenging. To improve research and care, a Canadian Pulmonary Hypertension Registry (CPHR) was created with pulmonary hypertension (PH) programs across the country contributing. Through my research I will describe the ß÷ßäÉçÇø PAH and CTEPH population from Calgary and Edmonton PH clinics.

The objective of the project is to build the Edmonton PH Clinic’s contribution to the CPHR and describe the demographics, disease severity, therapy, and mortality of the PAH and CTEPH populations in ß÷ßäÉçÇø. Adults patients that give consent and have PAH or CTEPH that are followed by the Edmonton and Calgary Pulmonary Hypertension Clinics will be analyzed. These patients’ charts will be reviewed, obtaining data from paper charts, the local pulmonary hypertension database, E-clinician, and/or Connectcare to build the Edmonton portion of the CPHR, including demographics, investigations contributing to diagnosis, symptoms, medication therapy, lung transplant listing and transplantation, and survival. It is anticipated that PAH patients will need progressive medication therapy over time, leading to lung transplantation or death, while the survival of CTEPH patients is dependent on whether they receive a specific type of surgery known as a pulmonary endarterectomy. The expectation is that survival in both diseases will be similar to other published PAH and CTEPH populations internationally. The data collected will ensure Edmonton’s participation in the CPHR, providing the foundation for future data collection. Edmonton is an important part of this national initiative. Through this project, we can develop a better understanding of ß÷ßäÉçÇø’s PAH and CTEPH populations to assist in further research and possible quality improvement initiatives. A key benefit being that we will provide information to improve the process of lung transplantation in this population.