Chronic inflammatory airway diseases include asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Together, these conditions contribute to an enormous burden of death and disability worldwide. It’s estimated that 10 to 15% of 13- to 14-year-olds in Canada are asthmatic. COPD affects close to half a million Canadians 35 and older, currently ranking 12th worldwide as a cause of lost quantity and quality of life and projected to rank 5th by the year 2020. CF is the most common, fatal genetic disease affecting Canadian children and adolescents.
There is compelling evidence supporting a hereditary pattern to virtually all of the major inflammatory diseases. For example, more than 1,000 CF-causing gene mutations have been identified. Although some mutations are associated with less severe disease, patients possessing the same mutations often show great variation in disease severity and progression. Significant advances in molecular genetics make it possible to discover the specific genetic variants that determine individual susceptibility to these illnesses.
Dr. Andrew Sandford is investigating the genetic variants that cause susceptibility to asthma and COPD. He is also focused on the role of genetics in CF. He works with a unique group of patient families who have previously been involved in studies to establish the associations between their genetic variations and their disease symptoms. A better understanding of the causes of inflammatory airway diseases will contribute to better prevention and/or intervention measures and more efficient treatment strategies.
An aneurysm is a permanent dilation, or ballooning, of a blood vessel or an artery to 1.5 times its normal diameter. It is usually a complication of atherosclerosis, a form of cardiovascular disease where the interior walls of blood vessels are blocked by a fatty substance called plaque. While most aneurysms are small, slow growing and rarely rupture, some are large, fast growing and at higher risk of rupturing. Aneurysm formation can result in hemorrhaging and death if not immediately repaired – the mortality rate after a rupture is 80-90 per cent. Aneurysms in the brain (cerebral aneurysms) can rupture and cause bleeding within the brain, resulting in a stroke. Ciara Chamberlain is studying a protease, Granzyme B, which is made and released by certain types of immune cells. Granzyme B may play a role in aortic aneurysms by breaking down structural proteins and causing thinning of the blood vessel wall. Building upon work in this area already conducted at the James Hogg iCAPTURE Centre, this research seeks to provide definitive evidence about the therapeutic potential for Granzyme B inhibition for the prevention of aneurysms in patients with mild or advanced atherosclerosis.
Cardiovascular disease is the leading cause of death in Canada. Atherosclerosis is a cardiovascular disease, in which the inside of blood vessels contain fatty growths known as plaques. Over time, these plaques become unstable and can break, resulting in blockage of blood vessels. This can lead to heart attacks, strokes and limb loss. Wendy Boivin’s research explores what makes a plaque develop, grow, and become less stable. She is focusing on a protein called Granzyme B, which is known to cause plaques. What is unknown is which of two possible approaches Granzyme B uses to induce plaque formation and atherosclerosis: either by entering blood vessel cells and killing them, or by breaking down structural proteins in the blood vessel. Wendy Boivin is studying the role of perforin, a protein that is required for Granzyme B to enter into blood vessel cells. By conducting a study that observes what happens when perforin is removed from blood vessels, she can pinpoint the pathway Granzyme B uses to cause atherosclerosis. Ultimately, this study may contribute to new therapeutic targets for combating this disease.
The World Health Organization estimates that between 100 million and 150 million people worldwide suffer from Asthma. The disease places a huge burden on the health-care system, with economic costs greater than of TB and HIV/AIDS combined. While less common than Asthma, Idiopathic Pulmonary Fibrosis (IPF) is a devastating disease since there is no cure or effective therapy. In North America and Canada there are over 200,000 patients with this disease. Of these more than 40,000 die annually. This is the same number of people that die from breast cancer annually. Currently we think that the pathology of both diseases follows a pathway similar to normal wound healing, although there is progression of the disease because the normal «braking» mechanisms do not function properly. As a consequence, too much connective tissue is produced. My research focuses on the cells that line the airways, called the epithelium and the cells that produce the connective tissue, called fibroblasts. Epithelial cells are important since they are the first cell in the lung that interacts with the air and are therefore most likely to be injured. We think that if the epithelium does not repair properly, it will signal the fibroblasts to continue making connective tissue inappropriately.
My research focuses on trying to identify why some children get asthma and others do not. By identifing specific environmental and genetic risk factors and determining how they work together to predispose children to developing asthma and other allergic diseases we can design better treatments. Studies have found a 1-in-5 risk of developing asthma if one parent has asthma. The odds rise to 2 out of 3 if both parents have asthma. However, in itself, a genetic predisposition does not ensure that asthma will develop. Asthma and allergic disease are the result of both genetics and the environment. The interaction between a genetic disposition and environmental factors is key in the development of – or in protecting against- asthma. I will use information from 250 French Canadian Asthma Families and two additional birth cohorts, and information from the town of Busselton Australia in my research. Home visits were conducted for all the families and children to collect information on environmental factors such as family history, number of children, parental occupations, daycare, pets, dust samples, infections, hospitalizations and medication usage. After reviewing the literature we have found 162 genes which may predispose children to developing asthma and we will be looking at these genes in conjuction with other environmental factors to try and better understand why some children develop asthma and others do not. Using statistical models we will look at what genetic and environment factors best explain why some children develop asthma and others do not. We will then do further laboratory experiments to try and identify these factors work together.
Heart failure is a disorder in which the heart loses its ability to pump blood efficiently. Despite recent advances in treatment, heart failure remains the leading cause of death in Canada. One in four Canadians suffers from heart disease, and more than 70,000 Canadians die from heart diseases each year. Treatment of heart failure is a major economic and social burden. The proteasome is a large multiprotein complex found in all cells, which breaks down unwanted or damaged proteins that have been “tagged” for elimination with a small protein called ubiquitin. The ubiquitin/proteasome system contributes to many cellular functions, including cell division, quality control of newly-produced proteins, and immune defense. Impairment of this system has been linked to several diseases, including cancer, Alzheimer’s and Parkinson’s diseases. It may also play a role in the development of heart failure. Tse Yuan Wong’s research is exploring the contribution of the ubiquitin/proteasome system to heart failure. This involves examining the functional changes of this system in heart failure and determining how it is regulated. He will also explore how disturbed proteasome function affects the progression of heart failure. This study will provide valuable insights into the mechanisms of heart failure, which could lead to novel therapeutic strategies that could have a huge impact on health care in Canada.
It’s well established that severe infection in critically ill patients can result in heart damage, but what causes this damage is unclear. One possibility is that heart muscle recognizes and responds to infectious pathogens and their products, triggering events within heart cells that ultimately lead to heart failure. Dr. John Boyd is researching the link between serious infection and cardiac dysfunction. The immune system uses Toll-like receptors to recognizes infectious products. Boyd aims to establish the role and function of Toll-like receptors in the heart, and what response occurs in heart muscle cells when incubated with infectious pathogens that are known to activate these receptors. Because Toll-like receptors also recognize and respond to tissue damage arising from ischemic heart disease (when there is a decrease in the blood supply to the heart caused by constriction or obstruction of the blood vessels) and heart transplant rejection, the research could have relevance beyond cardiac response to acute infection. Ultimately, Boyd aims to provide novel insights into the connection between the heart and immunity, which could lead to the development of new strategies to improve outcomes in diseases that involve inflammatory responses of the heart.
HIV/AIDS continues to be a major health issue in Canada, twenty-five years after the first cases were reported. About 58,000 Canadians, including 13,000 BC residents, are infected with HIV (the human immunodeficiency virus that leads to AIDS), and the incidence appears to be rising. A rough estimate sets the medical costs of caring for people with HIV/AIDS at more than $800 million a year. But rapid treatment advances make medical costs a moving target. Karissa Johnston is using the computer simulation model she developed in her earlier MSFHR-funded research to more accurately estimate the annual and lifetime medical costs of treating people infected with HIV. Johnston has designed a series of modules to measure the amount of HIV virus in peoples’ bloodstream (called the viral load) over their lifetime, their initiation and adherence to antiretroviral medications, their use of health services, and their survival time with different treatment regimes. As new treatments or data become available, individual modules can be updated without affecting the others. This information can help health care providers assess the costs and effectiveness of different treatment options. For example, antiretroviral medications successfully suppress viral load, reducing the risk of passing the infection during a sexual encounter. Even though the medications are costly, this tool will show if they ultimately result in costs savings due to a reduction in new infections.
In 1997, congestive or chronic heart failure (CHF) was the primary cause of death in British Columbia and in 2000, it was the most common cause of hospitalization for Canadians over the age of 65. Multidisciplinary interventions, including education, follow up and self-management strategies have been shown to improve quality of life and decrease subsequent hospital admissions among people with CHF. However, up to 50 per cent of hospital readmissions for CHF occur because patients have not learned to manage and monitor their condition effectively. Biljana Maric’s research is investigating the feasibility of Internet-based self-monitoring for CHF patients. Participants will log on to the study website each morning, enter their current body weight and answer five questions about their health status and any symptoms they are experiencing. A nurse will log on to a secure database to monitor responses and follow up with participants when responses trigger an alert. Biljana’s study will examine patient and staff uptake, and assess the impact of the program on patient quality of life and self care. If adopted, Internet monitoring of heart patients could decrease the health care costs associated with heart failure readmissions, alleviating some of the financial burden on the health care system while improving patient health outcomes.
The economic model of rational addiction was a breakthrough in the economic theory of consumption of addictive substances. This model’s aim is to reliably estimate an addict’s change in consumption of an addictive substance due to a change in the drug’s price or the price of another drug to which the individual is addicted. Polydrug abuse within populations of heroin addicts has been observed within health services research literature for some time. Suggestions have been made to target treatment interventions and outcome assessment to multiple drugs, rather than a single drug in clinical trials involving substance abusers. Despite this, relatively little epidemiological research has been carried out to evaluate the effectiveness of different modes of treatment for drug abuse in polydrug addicts. Bohdan Nosyk is researching whether individuals addicted to more than one substance (e.g. heroin and cocaine) display some association in their consumption patterns of these substances. If there is a significant association in consumption, focusing treatment on one addiction may be ineffective given the increase in consumption within the other (untreated) drug addiction. This study will survey individuals addicted to multiple drugs residing in Vancouver’s Downtown Eastside to determine the relationship between illicit drug prices and consumption. Research into the addicted illicit drug consumer’s behaviour – in particular, how the consumer substitutes between substances and which drugs tend to complement one another – will provide policy-makers with evidence on which to base future directions in the treatment for addictive substance abuse.
