From the Allergic Living Archives. First published in the magazine in 2008.
If you have a child with peanut allergies, other parents will say to you: “Nobody was allergic to peanut butter when I was a kid.” If a cat swishing through a room starts you wheezing, you’ll get asked: “How come so many people have asthma?” Both are reasonable questions, variants on the broader million-dollar one: “Why do so many people have allergies today?”
If you want an easy answer, allergy experts will simply say they don’t know. But what they mean is – they don’t know entirely. The fact is that scientists understand a lot more about allergic disease than they did a decade ago. There are still gaping holes in their knowledge, but as they continue to fill in the pieces to the puzzle, what they are finding is fascinating and often surprising. In the following investigation, Allergic Living examines what science knows so far about why allergies occur.
In the Beginning
When a baby is born, its immune system is a work in progress. “You’re born with a naïve, allergic-skewed immune system,” explains Dr. Michael Cyr, an allergist and immunologist at McMaster University in Hamilton, Ontario. This is what scientists call the Th2 mode.
During the first days, weeks and months of life, as the baby comes into contact with various germs, bacteria, viruses and infection, the system is supposed to start learning to distinguish between what is harmful and what is benign.
Some allergists liken the emerging immune system to a toggle switch or a reset button: we’re all born in that Th2 mode and then that first bout of sniffles at eight weeks or the ear infection at four months begins to “switch” the immune system over from Th2 to Th1 mode or fighting bacterial infection mode.
But in the person with a genetic inclination to allergy, something misfires and the switchover doesn’t happen properly. Cyr, who’s a researcher with AllerGen (the Allergy, Genes and Environment Network), says that why this process happens easily for some people but not for others remains unclear, and may depend on a confluence of factors.
The young child who doesn’t get switched over is now atopic – predisposed to developing an allergic response to a trigger such as cat dander or ragweed pollen or peanuts. After breathing in or consuming one of those, the child’s immune system creates allergy antibodies – specifically Immunoglobulin E or IgE antibodies – to guard against the offending trigger. The next time the immune system encounters it, the IgE will go on the defensive, setting off a cascade of allergic symptoms.
Though genetics are a large contributing factor to whether a person becomes allergic, scientists haven’t found one specific allergy gene. “It’s becoming clear that it’s not a gene, it’s a whole series of genes,” says Cyr. Something has changed to increase the number of us who are developing allergies, says Dr. Dennis Ownby, a professor of pediatrics and the head of allergy and immunology at the Medical College of Georgia in Augusta.
“What seems to have happened over the last three decades, at least in developed countries, is that genetic ability [to be allergic] has become more prominent,” he says.
Just how much have allergies and asthma grown? Figures from the World Allergy Organization reveal the global prevalence of asthma has increased by an astounding 50 per cent every decade for the past 40 years. In North America today, leading allergy organizations estimate that about 24 million Americans and three million Canadians have asthma.
In the past decade alone, the prevalence of food allergy, once an uncommon condition, has skyrocketed. The Food Allergy & Anaphylaxis Network*, the U.S. education group, estimates that about 12 million Americans – 4 per cent of the population – now contend with the disease. The Canadian rate of food allergy is estimated to be comparable. Peanut allergy alone has doubled in young American kids.
In our modern world, allergy has spread like wildfire. Scientists are certain that genes alone can’t be the whole reason why. “The genetic pool does not dramatically change over decades,” notes Cyr. “So it’s obvious there’s something else going on.” And that something appears to be our environment.
Getting to the Dirt
While references to asthma date back to ancient Chinese medical texts, the real story of our modern understanding of allergy begins in earnest in 1989. It was a heady year, with the fall of Berlin Wall and the beginning of the opening up of the former East bloc. A team of German scientists decided this presented a great opportunity to compare the prevalence of asthma in Leipzig (former East Germany) and Munich (former West Germany).
Here were two highly similar gene pools of people who had been living in very different societies and conditions. “At that stage, everyone, including us, believed that air pollution was causing asthma and allergies,” says Dr. Erika von Mutius, who was then a young pediatrician and team leader, and who today is a professor and head of the asthma and allergy department of Munich University’s Children’s Hospital.
When the findings began coming back showing that there was considerably more asthma in modern, Western, hygienic Munich than among the study group living in Leipzig with its billowing factory smokestacks, the researchers were incredulous.
“It was so opposite what we’d anticipated,” recalls von Mutius on the phone from Munich. “We didn’t believe it, so we thought it was a mistake in data entry and re-entered all the data.” But the data were right, and the results were published in 1992.
*Update: The organization FAAN has been renamed FARE.
That year, von Mutius took her research with her to Tuscon, Arizona, where she worked on a fellowship at the University of Arizona under her mentor, Dr. Fernando Martinez, the well-known asthma researcher who today is the director of the Arizona Respiratory Center. One day he read a medical paper out of Britain about something called “the hygiene hypothesis”.
The author of that paper, an epidemiologist named David Strachan, had conducted a study of over 17,000 British children and found that youngsters who had older siblings and were exposed to more infections and bacteria early in life were less likely to develop hay fever or eczema. Writing in that same pivotal year of 1989, Strachan had theorized that smaller family sizes and higher levels of hygiene in modern Western homes may have been contributing directly to the increased prevalence of allergy.
Martinez was intrigued. What, he asked, would happen if von Mutius took into account the sizes of her East German and West German families? The data were incomplete, but it was the less allergic East Germans who clearly had more children per family. She and Martinez followed up with a study comparing family sizes and allergy in Munich and Leipzig (and a neighboring city).
A pattern emerged: the most allergic were the Munich kids with one or no siblings; the least allergic were the East Germans with two or more brothers and sisters. Children in the larger families were being exposed to more germs. It fit with this rudimentary hygiene hypothesis. “It took off from there,” says von Mutius.
Back to the Land
Where the hygiene theory took off to was a place caught in a time warp: the traditional European farm, where father, mother and children still do all the manual labor, from milking to sweeping out the stables. The idea to look at the family-run farm actually came from a school doctor in a Swiss village. He noticed that farm children under his care, unlike other kids, never seemed to get hay fever.
Struck by this observation, he began writing to allergy experts in Basel, research colleagues of von Mutius. At first they were skeptical of the rural doctor’s notion, but then a few Swiss professors ran a small study. The findings were compelling: there was markedly less allergy and asthma on the farms in question. This merited further examination.
And so in 1998, von Mutius began her long-running involvement in a series of European farm studies that have become the underpinning of current allergy research. The first was ALEX (the Allergy and Endotoxin Study), involving scientists from Germany, Austria and Switzerland. The team began gathering and publishing data, and the central findings were consistent: children who lived on these farms were significantly less inclined to have allergies and asthma than children in the neighboring village.
Then came other major studies of the family farms: the multi-center PARSIFAL study of children enrolled in Steiner schools (akin to Waldorf education), which involved 6,600 pupils in five countries; and the PASTURE study, which examined children’s exposure to microbes on farms across Europe. With each study, with each new set of samples of stable and mattress dust, with each new set of blood-test results for environmental and food allergies, a little more was known. “We are getting somewhere,” says von Mutius, taking stock for a moment. “There are now 17 papers [since 1999] that all show the same things.”
They reveal what’s termed “the farming effect,” a phenomenon that protects against allergic disease. Von Mutius and her colleagues have narrowed the effect down to three key factors: livestock (specifically cows, pigs or poultry); type of fodder (for instance, whether it’s fresh grass or hay); and drinking of raw farm milk.
The findings have been generally consistent – about 1 to 2 per cent of the farm children in the studies had asthma compared to 12 per cent of local, non-farm children in control groups. “I’m completely convinced that this is real,” says von Mutius. “The question is – are we going to be able to solve the puzzle.” She chuckles: “For that we need a lot of luck.”
To that end, today von Mutius is co-leader of a massive European Commission project called GABRIEL, which involves 14 countries and 40,000 test subjects. Among its goals is to identify what in those three key elements of livestock, fodder and unpasteurized milk confers protection against allergy, whether it acts alone or in combination with other farm factors as well as the genetic background, and how this all takes place.
For a while, some thought a key was endotoxin in the barns – that’s the membrane of certain bacteria that stimulates the immune system and can cause illness. But fungal spores are also proving important. At this stage, von Mutius finds endotoxin a minor player. “It’s not just endotoxin, of that I’m pretty sure. We think it is microbial factors on the farms – it’s probably anything that’s bacterial, or molds, maybe yeasts. We’re trying to develop new tools to measure those exposures.”
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.”