Air pollution and asthma: Modifying factors in a public health context

In reaction to air pollutants, asthmatics may experience an “”asthma exacerbation”” characterized by the narrowing of their airways. This may lead to a shortness of breath that may require urgent medical attention. One source of air pollution associated with asthma exacerbations is diesel exhaust. How and why diesel exhaust causes exacerbations is unclear, but one hypothesis is that it causes “”oxidative stress””, which is damage to cells and body tissues due to certain chemical characteristics. Ongoing exposure to traffic-related air pollution can also result in new asthma in previously healthy individuals. Dr. Christopher Carlsten is working to understand how different air pollutants, particularly diesel exhaust, influence asthma. He is trying to determine whether diesel exhaust creates oxidative stress, and, if so, if that stress is responsible for airway narrowing in human asthmatics. In his laboratory, diesel exhaust is generated in concentrations typically found in mining operations or in busy bus terminals. Volunteer subjects inhale the exhaust for two hours – a short exposure time has no permanent effects but does produce mild, temporary changes – and changes in oxidative stress and airway narrowing are measured. In some subjects, other typical environmental allergens such as tree and grass pollen are added to see if they worsen the effect of diesel exhaust. In addition to this work, Dr. Carlsten and colleagues are following a group of more than 20,000 children from birth to see how their exposure to such pollution may lead to new asthma. Dr. Carlsten’s research will lead to a better understanding of diesel exhaust-related airways disease and will lead to measures to protect Canadians exposed to traffic-related pollution. This research aims to inform recommendations for or against changes in fuel composition and/or personal measures to bolster anti-oxidant levels. Dr. Carlsten’s work to understand the effects of air pollution on asthma development should inform interventions regarding pollutant exposure in children.

Towards evidence-based public health for sex workers in British Columbia

Youth and women working in Vancouver’s sex industry are among the most marginalized and vulnerable in Canadian society. The persistently high rates of health-related issues, violence, and mortality among sex workers, both in Canada and globally, highlights a desperate need for renewed public health interventions targeting the reduction of harms in this industry. Dr. Kate Shannon is working to investigate the different factors influencing the health and safety of youth and women working in the sex industry in Vancouver. Her team is studying the social (violence, work conditions) and structural (laws, regulations, urban renewal) contexts of sexually transmitted infection (STI) in this population. Specifically, her team is examining the different factors that influence the worker’s negotiating power during transactions and how this influences the risk of HIV/STI acquisition. Her research will involve the study and long-term follow-up of two groups of women: (1) 500 existing and new adult women working in both the street and indoor sex industry; and (2) 250 female youth aged 14 to 20 years who have exchanged sex for money, drugs, gifts, shelter, or other commodities in the previous 30 days. By evaluating and integrating different types of data, including individual mapping and neighborhood environment data (including violence and housing) from publicly available sources, she hopes to identify policies and harm-reducing interventions for this population. This study is among the first prospective studies of sex work in North America. Dr. Shannon’s team possesses a wealth of expertise in observational and intervention research, policy, and sex work. They are uniquely positioned to conduct this study, which aims to directly improve the health of some of the most marginalized youth and women in Canadian society.

Finding a cure for tendinopathy: a translational biology approach

Repetitive-use tendinopathy, formerly known as tendonitis, is a major cause of repetitive strain injury (RSI). The occupational costs of RSI are enormous: work-related injuries cost Canada $8.6 billion annually and an estimated one-third of workers' compensation costs in industry are due to RSI of soft tissues, particularly tendons. In 2001, 2.3 million Canadians reported an RSI, and the average time lost from work per case of tendon-related injuries was 79 days (Source: StatsCanada 2001). Despite the enormous clinical, societal, and economic significance of RSIs, there is only limited understanding of the mechanisms that cause them.

In order to establish new treatments for RSI, Dr. Alexander Scott has established an innovative tendinopathy research program. He is incorporating a multi-disciplinary approach from basic to clinical science, which integrates a number of different methods, including molecular and cell biology, biomechanics, and rehabilitation science. His work will focus on the role of new blood vessel formation as a feature of chronic tendon injury. This work promises basic insight into the biology of RSI as well as directly applicable knowledge to develop new therapeutic strategies. This will be the first research program in Canada to have a primary focus on the biology of work-related tendon overuse injuries using a multidisciplinary approach. The ultimate vision of this program is to find better treatments for work-related tendon injuries.

SALOME (Study to Assess Long-term Opioid Medication Effectiveness): double blind randomized controlled trial comparing the effectiveness of diacetylmorphine vs. hydromorphone for the treatment of …

Injection-drug users are extremely susceptible to drug-related health risks, including HIV, hepatitis C and overdose. Although treatments for drug addiction are available, they are not always effective for those with the most severe cases of addiction. A key issue is many members of this vulnerable population remain outside the health care system, which exposes injection-drug users and those in their immediate communities to drug-related health risks. Previous research studies in Europe and Canada have shown that medically prescribed heroin can effectively attract and retain injection-drug users into the health care system and can ultimately improve the health of this vulnerable population. Unfortunately, the negative stigma attached to the medical use of heroin is a barrier to its implementation in many settings. However, an alternative strategy was suggested by a Canadian study, which demonstrated that a small group of participants receiving a licensed pain medication experienced similar health improvements as those receiving medically prescribed heroin.

Dr. Eugenia Oviedo-Joekes’ research is studying whether alternative drug addiction treatments can be used to reach vulnerable populations remaining outside the health care system. She is conducting an innovative clinical trial to test whether licensed pain medications can successfully treat the most severe cases of heroin dependency and is studying how this approach compares to medically prescribed heroin. After patients are effectively stabilized with injection treatment, she will determine if pain medication administered as an oral liquid can be used instead of injections.

Dr. Oviedo-Joekes is focusing her work on a subpopulation of women and Aboriginal people that have experienced high rates of victimization, including physical and sexual abuse, or violent or traumatic experiences, which dramatically impact their health. She hopes these treatments will directly benefit those with the most severe cases of heroin addiction and she will also measure the beneficial impacts in their communities.

Optimizing health outcomes in arthritis care: Promoting knowledge translation through digital media

Arthritis consists of more than 100 types of conditions and is the most common cause of severe chronic pain and disability in Canada, affecting 4.4 million Canadians. While effective treatments are available, they are not consistently prescribed by health professionals or used by patients. Currently, researchers and research funding agencies have focused on tailoring research findings to specific audiences via methods such as plain language summaries, education sessions, public symposia, and media events. However, the impact of this information can be limited if it is provided at a different time and place than when people need to use it. Digital media offer a range of applications – social networking tools, interactive games, animation, and video/audio recordings – that provide tremendous flexibility for delivering “just-in-time” information when and where it is needed by the user. The depth, richness, and accessibility of this information are infinitely greater when conveyed via digital media than the current methods of publishing research results.

The goal of Dr. Linda Li's research program is to optimize the health of Canadians with arthritis by studying how people make treatment decisions and by improving the use of effective treatments using innovative digital media tools. Her program focuses in three areas: 1) understanding how patients with arthritis make treatment decisions; 2) evaluating models for health professionals who provide arthritis care; and 3) developing digital media interventions and evaluating their effectiveness to improve clinical practice, treatment decisions, and patient health.

This research program focuses on improving the health outcomes of people with arthritis by harnessing the engaging power of digital media to deliver research knowledge when and where it is needed. This approach is unique because it targets both patients’ behaviors and health professional practices to help close the gaps between what we know about arthritis management and the actual use of effective treatments. This innovative combination of health and digital media will help us modernize the way we deliver evidence-based treatment information for the 21st Century.

Immunological basis for infections in prematurely born infants

Pre-term babies, those born before week 37 weeks of gestation, are more susceptible to invasive infections than full-term babies. The smallest babies born “extremely” premature (those born before 32 weeks, or approximately 1,500 grams or less of birth weight) suffer the greatest burden of infection among all age patient age groups in BC and other developed countries in general. About one in four “extremely” pre-term babies suffers from an invasive infection, which adds up to more than 8,760 new invasive infections in North America each year. In addition to the immediate health risks, such as a major loss of cardiorespiratory function or death, these infections may lead to long-term physical and intellectual handicaps in these children.

The work of Dr. Pascal Lavoie aims to understand why pre-term babies are so vulnerable to infections caused by common micro-organisms. Dr. Lavoie and his team are examining the way that babies’ immune cells work early in life to determine if this differs from the function of mature immune systems. In order to do this in a way that is completely safe to babies, he takes advantage of scavenged blood samples (he uses, for example, placental blood normally discarded at birth) analyzed using sophisticated technologies to extract detailed information about the human immune system.

Dr. Lavoie also aims to understand why the immune system of pre-term babies appears underdeveloped and what impact therapeutic manipulation of the latter may have on diseases such as bronchopulmonary dysplasia: a chronic form of neonatal inflammatory lung disease which appears to be caused by excessive activation of the immune system during infection. Ultimately, Dr. Lavoie hopes that a better understanding of the immune systems of pre-term infants will help researchers and doctors develop better treatments to boost immune defenses and prevent the dreadful consequences of infections in vulnerable newborns.

ATP-sensitive potassium channels: electrical signaling of cellular metabolism

Many types of rare inherited genetic disorders profoundly affect children and their families. While disorders like Anderson syndrome, Bartter's syndrome, and DEND (Diabetes with Epilepsy and Neuromuscular Defects) affect different organ systems and manifest with different symptoms, these diseases are all caused by genetic mutations in the KIR family of proteins. Mutations in KIR proteins can also be involved in less severe symptoms, including cardiac arrhythmias and vascular defects. The KIR proteins are a family of ion channels known as inwardly rectifying potassium channels. These ion channel proteins form pores in cell membranes, which can be switched on or off, by opening or closing “gates” in the ion-conducting pore. When the gates are open, charged ions can pass across the membrane, generating electrical currents and influencing the membrane voltage. These KIR proteins regulate a diverse set of processes, from beating of the heart to hormone release from the pancreas, and can be influenced by a number of cellular processes and molecules.

Dr. Harley Kurata’s work is focused on the KATP channel, which is a member of the KIR family and is regulated by the “fuel” (ATP) that drives all cells. The KATP channel can sense the metabolic state of cells and serves as a critical trigger for insulin release from pancreatic beta-cells. KATP channel mutations are now recognized as an important cause of genetically inherited insulin disorders, ranging from diabetes (too little insulin released) to hyperinsulinism (too much insulin). Dr. Kurata's team hopes that by identifying the specific mutations involved in KATP, therapeutic approaches to both diseases can be developed. KATP channels are also present in the heart, and although their role in cardiovascular function remains enigmatic and controversial, further investigation of this unique set of proteins has the potential to impact other diseases.

Improving chronic cardiovascular disease management in ethnocultural patients

Cardiovascular disease is a leading cause of death and disability worldwide. Long-term disease management approaches are effective at reducing the risk of death and disability in patients with cardiovascular disease. Canadians of South Asian and Chinese ancestry are more likely to die from heart disease or stroke than other Canadians and there is emerging evidence that these groups may have poor chronic disease management. Optimal chronic heart disease management may be significantly impaired by language barriers, a limited understanding of health determinants, and potentially differing cultural views of heart disease and treatments. The goal of Dr. Nadia Khan’s research program is to improve chronic cardiovascular care for Canadians of South Asian and Chinese ancestry. She is currently undergoing a very large study of 600 South Asian, 600 Chinese, and 600 Caucasian patients discharged with acute heart attack or unstable angina from hospitals in Vancouver, Toronto, and Calgary. The objectives of her research program include: (1) determining differences in chronic cardiovascular disease management between South Asian, Chinese, and Caucasian patients; (2) identifying the underlying patient barriers associated with poor care for each of these groups; and (3) using this information to develop targeted and culturally sensitive interventions in chronic cardiovascular disease management. Working alongside health care workers, ethnic community members, and decision makers, Dr. Khan will be developing and testing the new strategies to ensure that they are acceptable and practical for each ethnic group. This is the first program to systematically evaluate how different ethnic groups manage coronary artery disease and to identify the cultural factors that may be linked with poor care. The evidence obtained from this study will be used to plan culturally sensitive care programs for those with heart disease who are from South Asian or Chinese ancestry. This program of research will partner with community members, health care workers, and decision makers to ensure that the interventions are relevant to policy and practice.

Optimal timing of delivery for high risk pregnancies

Early delivery (delivery before spontaneous labour by induced labour or caesarean birth) is often considered for high-risk pregnancies to prevent stillbirths and protect the mother from developing pregnancy complications. However, the optimal time for early delivery is often unclear. Although birth between 37 and 41 weeks of pregnancy was once considered ideal, babies delivered early at 37 to 38 weeks are more likely to have breathing complications than babies delivered later. Deciding when a higher-risk pregnancy should be delivered therefore involves balancing the risks to the baby from delivering too early against the risks to the mother and fetus from delaying delivery too long.

Dr. Jennifer Hutcheon's research focuses on better understanding the risks and benefits associated with early delivery and how they change on a week-by-week basis. She is studying the optimal timing of delivery for repeat caesarean surgeries (a caesarean scheduled after the caesarean delivery of a previous child). Delivery before 39 weeks is not recommended because it will increase the risk of breathing complications in the infant at birth. However, planning the surgery for a later week of pregnancy makes it more likely that the mother will go into spontaneous labour before her scheduled surgery. Early work has found that despite the risks to the baby, 62% of repeat caesarean births in British Columbia happen before 39 weeks.

Dr. Hutcheon will review the medical records from all pregnancies in BC between 2001 and 2010 stored in the BC Perinatal Database Registry to better understand the factors causing the high rate of early-term delivery in women having repeat caesareans and the potential risks associated with delaying delivery until 39 weeks or later. Using large population and clinical databases, she will also examine the week-by-week risks of delivery and delaying delivery in other higher-risk populations, such as twin pregnancies and older mothers.

Dr. Hutcheon will use the information she obtains to calculate the week-by-week risks for mother and infant associated with delivery and with delaying delivery, in order to highlight the time in pregnancy at which both risks are lowest. She anticipates that her work will help inform best practice in the province and will ultimately have a positive influence on the health of babies born in BC.

Auto-inhibited regulatory proteins: New approaches to characterize and identify these important switches in cell communication

The impact of cancer on our society is enormous. According to the Canadian Cancer Society, an estimated 9,300 people will die of cancer in British Columbia in 2011, with 22,100 new cases being diagnosed. Despite the many different treatment options that have been developed in the past several decades, the high death rate demonstrates that new and better therapeutic approaches are necessary. Cancer is often caused by the disruption of cellular control and regulatory mechanisms. One such regulatory mechanism known as “”autoinhibition”” allows proteins in the cell to switch their own function on or off. Genetic mutations or viral infections can result in the disruption of this autoinhibitory function, which can lead to a continuous activation of these autoinhibitory proteins. This can result in cell changes and can ultimately lead to cancer. Dr. Joerg Gsponer is taking a new approach to understanding how cancer develops and, ultimately, how it may be controlled. His research group is is aiming to improve our understanding of the mechanisms of autoinhibition with the help of computational methods. His team will develop new computational algorithms that will help identifying proteins in the cell that are regulated by autoinhibition and reveal how the autoinhibition works and how it is disrupted in the disease case. Ultimately, this will further our understanding of how cancer develops and will hopefully help to identify new drug targets for cancer therapy.