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| Dr. Allan Becker, Dr. Anita Kozyrskyj, and Dr. Michael Moffat are part of the team researching the early origins of asthma. | ||
The third week of September represents an annual peak in illness for the millions of asthma sufferers around the world. Although smog and ragweed pollen are the likely culprits, no one is certain-and this is just another unknown confronting researchers trying to understand this disease.
"We think we should know everything there is to know about asthma," says Dr. Moira Chan-Yeung, an asthma researcher based at the University of British Columbia. "It's a disease that's been recognized for centuries but we spend millions and millions of dollars and we're still finding out new things each day."
Chan-Yeung is a member of a new research team studying the genetic and environmental factors that cause asthma. The team is receiving funding through the Institute of Infection and Immunity's New Emerging Teams (NET) grant program. This is the first time all seven members will be working on the same project, titled Origins of Asthma in Childhood: The Role of Gene: Environment Interactions (see table).
| Dr. Allan Becker, team leader | University of Manitoba | Asthma clinician specializing in childhood asthma |
| Dr. Anita Kozyrskyj | Manitoba Centre for Health Policy, University of Manitoba | Epidemiology, population health |
| Dr. Kent HayGlass | University of Manitoba | Immunology |
| Dr. Michael Moffatt | University of Manitoba | Community and aboriginal health |
| Dr. Andrew Sandford and Dr. Peter Paré | University of British Columbia | Genetics |
| Dr. Moira Chan-Yeung | University of British Columbia | Environmental disease |
Where historically, research into asthma has focused on management of the disease, this team will focus on the causes, says team leader Dr. Allan Becker. "The bottom line is that the best we have to offer right now is control of asthma and other allergic diseases that ideally, we'd like to cure." However, the goal of this team is not to discover a cure, says Becker, but to identify factors that could be influenced to prevent asthma from developing.
Those who have never felt the suffocating grip of an asthma attack are largely unaware of how serious the disease can be. Becker, an asthma clinician, says, "That's the sad part-there's probably no disease where there's a larger disconnect between the ability to control the disease and actual control." Treatment and management of asthma is complex; a given patient must avoid all triggers, and may have up to three different inhalers.
Worse, asthma, the most common chronic disease of children, is on the rise. In the last quarter century, says Becker, the prevalence of asthma and other allergy-associated diseases has increased dramatically-but strangely only in developed countries. Because asthma is known to be strongly heritable, "the change in prevalence ought not to be due to genetic change but our belief really is that this is due to changes in our environment," says Becker.
It's long been recognized that asthma is the product of both genetic and environmental interactions, but where most research has focused on one or the other in isolation, this team will examine these factors together. Using Manitoba's health care databases, the researchers will evaluate the health care services provided to children born in 1995, such as medication, physician contact and institutional care. Children identified as having asthma will be invited to participate in the study, as will an equal number with no indication of either asthma or allergy. The children's family and environmental situations will be assessed, and dust from their homes analysed for allergens and endotoxin (a component of gram-negative bacterial cell walls). All children will be clinically re-evaluated for asthma and allergies. Blood samples will be collected for first immunologic, and finally genetic analyses.
The NET grant will also allow the team to further investigate the grounds for the "hygiene hypothesis," which attributes the increased prevalence of asthma in developed countries to inhabitants' decreased exposure to bacteria and endotoxin, resulting in improperly developed immune responses. Within developed countries, "they found that children growing up on farms, particularly those that raise animals, have significantly less asthma and allergies compared to children who are growing up in cities," says Chan-Yeung. Endotoxin is generally recognized as playing a role in the development of asthma in children, but the nature of this role has not been determined.
A province with a large aboriginal population, Manitoba provides the opportunity to study allergy and asthma in aboriginal children-a largely undeveloped research area. In aboriginal children of both rural and, to a lesser extent, urban communities, there is a lower incidence of asthma than in Caucasian communities. The researchers hope to learn not only why there is a difference, but also how to maintain it. Becker cites fears that asthma is an epidemic in the making in aboriginal communities that could reach proportions similar to the diabetes epidemic already raging there. He hopes the team will be able to figure out what the triggers are, and use this information to make changes or improvements in the aboriginal communities. Dr. Michael Moffatt is already working with the Centre for Aboriginal Health Research in Winnipeg, Man. to facilitate access to these communities, and says that the main advantage of this study to the aboriginal population will be the potential for prevention of future asthma and allergy-related illness. Dr. Andrew Sandford, who will be working on the genetic aspect of the project with Dr. Peter Paré, adds that aboriginal children could have different variants of the genes involved in causing allergy and asthma, genes that would not be found in Caucasian children.
The in-depth immunology work planned will also represent an expansion of that field in allergy and asthma research. "We'll be looking more at the cellular level," says Chan-Yeung, "for example, in the hygiene hypothesis, what kinds of cells are being activated and what's the mechanism?" As well, Dr. Anita Kozyrskyj's work with the health care databases, which contain information on all of the children born in Manitoba in 1995, will identify subjects to take part in the study, as opposed to beginning with, for example, children known to have been treated for asthma by a particular clinic. Dr. Peter Paré describes this approach as very powerful, "because you can then generalize back to the whole population. It would be more representative of the general population than most studies."
Becker forecasts that the early results of the team's work will begin translating into benefits for asthma patients within the year. The team expects that a thorough analysis of the interactions among genes and the environment will take several years, at which point it may be possible to pinpoint, prenatally or at birth, children at risk. Paré adds that in the shorter term, treatments might be tailored to individuals' genetic underpinnings for differences in their immunologic responses as asthmatics, potentially greatly increasing the precision of clinical trials and the treatment of individual patients.
Sandford says being part of the NET program is beneficial for each member of the team. "If we're thinking about which genes we should look at, it's much better that we talk to someone like Kent (HayGlass) who has a lot more in-depth knowledge of that immunology than we do." HayGlass appreciates that CIHR and III are supporting a research area that has such a high public profile. "It's not something obscure that my neighbour across the street would say, 'That must be nice but I haven't got a clue what you're working on.' It has tremendous relevance for all Canadians." HayGlass also appreciates being able to develop a research area where he believes there is a strong opportunity to advance the field, through taking a multidisciplinary approach.
Becker agrees, saying that the funding behind the team allows the research to be performed on a highly efficient level. "I don't think this would have happened without the request for proposals for the NET by CIHR and the Institutes, and I think that's one of the single best changes that I've seen in the approach to funding."
