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.”
CHILD’s researchers are examining all the environments of the babies. They collect dust, mold, air and blood samples, and will retest at specified intervals for comparison. The researchers ask for the very first bowel movement of newborns in the study. This is no joke: they want to know what bacteria the brand new baby has in his gut, and then compare those bacteria to what’s found in the intestines over time, up until the age of 5. They are trying to understand, Turvey says: “Are there protective bacteria or bad bacteria?”
Bacterial exposures are fascinating if complicated. Dr. Malcolm Sears, the epidemiologist who is director of the CHILD project, explains that how a person’s immune system will respond to a given bacteria will vary, and may depend on which bacteria and the quantity involved. “Certain genetic structures may make a substance like endotoxin, for instance, protective in some people and increase allergies in others. It’s not neutral, it can go either way depending on the genetic background. It’s not always protective,” says Sears, who is a professor of medicine at McMaster University and research director of the Firestone Institute for Respiratory Health at St. Joseph’s Healthcare in Hamilton.
When we speak of “good” bacteria, probiotics leap to mind, those so-called “friendly” micro-organisms that are beneficial to the gastrointestinal system. Could introducing them to a diet contribute to allergy prevention? Von Mutius sees indications that probiotics “might work,” but says the definitive study has yet to be produced.
There is something more apparently protective about the raw milk in the European farm studies, but von Mutius and her team do not yet know precisely what bacteria are making a difference, or whether the heating and denaturating of proteins is at play. She is not promoting the drinking of untreated farm milk, noting there are good reasons for wanting to kill pathogens in such a dietary staple. However, pasteurization as we know it has had a good run; Louis Pasteur invented it back in the 1860s.
In future, there may be practical applications from the European findings about raw milk. “You don’t want the pathogens, but maybe there are other ways,” she says. “I think we need to be clever and creative and find ways to do it.”
Like the researchers in CHILD, she and her team consider the farms they’ve studied to be a specific environment. This is a cloistered and natural environment – a big Petri dish of microbes and clues from a time that’s largely passed. We can’t all go back to live on the farm, but this unique environment may divulge answers to help bring the allergy epidemic under control.
From Cows to Dogs
In the urban environment, of course, there is one similarity to the traditional farm. We do still live among animals: those we keep as pets. As news spread from the European farm studies that exposure to cows, pigs and poultry was helping to protect against allergic disease, scientists began to wonder – could this protection be elicited from non-working animals, specifically dogs and cats?
Dr. Dennis Ownby is one of the leading researchers in this area. In 2002, he and a team of researchers from Henry Ford Hospital published findings in the Journal of the American Medical Association that were surprisingly contrary to the long-held belief that pets in the home would lead infants to develop allergies.
Ownby’s group conducted a study of 474 healthy Detroit children from birth to age 6, examining how exposures to cats and dogs affected the participants’ rate of sensitization to common allergens, including the animals themselves, mold, ragweed, grass and dust mites. The results showed that when infants in the first year of life lived with two or more dogs (or dogs and cats in combination), their risk of developing allergies at 6 or 7 years old was less than half (15.4 per cent) that of kids who hadn’t had any pet exposure (33.6 per cent).
In an interview, Ownby said: “There is something about being around an animal that changes the immune system so that you’re less likely to be allergic to anything.” (However, what remains the case is that if an individual in a household develops pet allergies, the animal should be found a new home.)
The topic had been contentious, with some studies making the case for, and some against pets as protective against allergies. However lately, research on dog exposure in early life has been uniformly positive. For instance, scientists in Munich in 2008 examined data from 3,150 children in two large population studies. The results, published in the European Respiratory Journal, revealed that in blood tests at the age of 6, children who had dogs in their homes during the first year of birth showed markedly lower rates of sensitization to inhaled allergens, such as dust mites, cats, grass and birch pollen.
The findings with cats have been more inconsistent, though a 2007 study of New York City children saw some latent positive effects. Scientists from Columbia University found that kids who had infant exposure to cats were more likely to develop antibodies to the animals and wheeze by age 3. Yet, those same children showed signs of a protective effect and were less likely to wheeze by the time they had turned 5. The researchers suggest that prolonged exposure to cats may produce a tolerance to the allergen.
What’s clear from the published research is that if there is a protective benefit to pet ownership, as with livestock, it happens early in life.