While her researchers are dealing in microscopic levels and minute interactions, von Mutius remains keenly aware of the bigger picture, of the “why” of allergies.
“Mankind has evolved with farm animals for thousands of years, and so probably there is an evolutionary system here that tells the immune system – ‘this is normal,’” she says. “Maybe that’s something the immune system needs in order to know that – this [protein] is harmless, this is nothing that needs to be recognized. In the absence of these factors, all of a sudden these proteins are being recognized as foreign where the immune system starts to mount an IgE response.”
Timing is Everything
What also appears to be important is when a child is first exposed to an environment that affords protection against allergies. It seems the earlier, the better. In 2001, the journal The Lancet published ALEX research in which children who were exposed to farm life from birth to age 5 were tested for allergies. Those children’s results were compared to levels from children who first came to live on a farm between the ages of 1 and 5. The most protected by far were the children who had lived on farms all of their lives until the age of 5, with fewer than 1 per cent developing either asthma or hay fever.
Von Mutius and her colleagues have deduced that the protective “farming effect” begins even before the baby is born. On the traditional farms, women continue to do chores through pregnancy, spending much time in the barn and around cattle. The exposure to the protective stimuli “already starts in utero, and we think the first two years in life are the most important ones,” says von Mutius.
Evidence of immunity before birth could be clearly seen in the umbilical cord blood of 922 babies in the five-country PASTURE study. The blood belonging to the farm babies was much less likely to contain allergy-causing antibodies to airborne triggers such as grass.
A consensus is forming around the importance of cord blood to allergy research. Back across the Atlantic, Cyr has been focusing on this at the McMaster University Medical Centre. His findings indicate that “the more allergic that mothers are, the less mature the cord blood’s stem cells appear to be in terms of the receptors that are important to the Th2-Th1 switch.” This could be a clue to future allergic status.
“It may well be that cord-blood stem cells are a marker,” Cyr says. They could indicate that “even from the day allergic kids are born, their immune systems are already less mature than kids from non-allergic parents.”
Umbilical cord blood will be examined in as many as 5,000 Canadian babies as part of the CHILD (Canadian Healthy Infant Longitudinal Development) study that recently received $12 million in funding from the Canadian government and AllerGen. The four-city study is designed to follow this group of children from pregnancy to the age of 5, and the first-phase of the project is well underway in Vancouver.
Dr. Stuart Turvey leads that pilot project, nicknamed Mini-CHILD, and he speaks excitedly about the prospect of having access to the cord blood of so many children and seeing “the quality of the immune response on the day the babies are born.” A pediatric allergist-immunologist at the University of British Columbia and B.C. Children’s Hospital, he, too, views the period from fetal development in the womb to 2 years of age as crucial, even in those individuals who don’t develop allergies until later.
What is in an Environment?
The primary interest of the big Canadian study is to identify environmental factors in urban living that put children at greater risk for allergies and asthma. In conversation, people tend to use the word “environment” as a catchall for the great outdoors and pollution or perhaps to mean one’s living space. But to epidemiologists and immunologists it’s much more. The womb, for instance, is one environment.
When Turvey speaks of the “environment” that the families enrolling in CHILD are exposed to, he breaks it down into several sub-categories. First, he sees the physical environments – the home, the daycare, the level of pollution outside them; the levels of dust, mold, tobacco smoke and chemical exposures inside; and whether pets are owned.
“And I think the infectious environment is important – factors such as cold viruses and bacteria in a baby’s body,” he says. He even views diet as another environment of stimuli that may influence immune responses: “environment is everything we’re exposed to.”
Turvey also describes a psycho-social environment, and here, he’s largely talking about the amount of stress on the mother in pregnancy or in the home after birth. Is there, for instance, a financial burden or might her support network be lacking?
“There’s evidence that stress can make asthma worse and may even set the scene for asthma predisposition in infants,” he says. He thinks these aspects, even in utero, “should not be underestimated.”