HEALTH

THE ALLERGY EPIDEMIC

Hay fever, asthma, eczema, peanuts. Millions are afflicted—and it’s about to get much worse

DANYLO HAWALESHKA June 5 2006
HEALTH

THE ALLERGY EPIDEMIC

Hay fever, asthma, eczema, peanuts. Millions are afflicted—and it’s about to get much worse

DANYLO HAWALESHKA June 5 2006

THE ALLERGY EPIDEMIC

HEALTH

Hay fever, asthma, eczema, peanuts. Millions are afflicted—and it’s about to get much worse

DANYLO HAWALESHKA

With her infant daughter Bridget Wadden dying in her arms, Lee Parpart says she would have sacrificed herself in a heartbeat if it meant saving her life. Parpart felt helpless as she watched her daughter’s face transformed by the ugly red swelling caused by anaphylactic shock, a severe allergic reaction in which the body attacks itself. How had it 34

come to this? The first, seemingly innocuous sign was in early 2003, when Bridget was five months old. Parpart and her husband, Ron Wadden, had gone out for an evening together for the first time since their daughter’s birth. Ron’s mother was babysitting Bridget, and gave her a bit of milk-based formula. (She’d been breast-fed up to that point.) Bridget’s face and neck broke out in hives, but the red welts had eased by the time her

parents arrived home. The incident alarmed ^ Parpart, but her family physician was “fairly f nonchalant,” she recalls. He said not to worry, ¿ it happens, just avoid dairy products. “We’d | really been given no indication of how seriz ous this could be,” Parpart says. “I didn’t ^ know that anyone could be life-threaten° ingly allergic to milk.” ¡Ü

Three months later, she and her husband g put Bridget in her stroller and went out to ^ soak up a wonderfully warm July day in their “ east-end Toronto neighbourhood. They ran into friends who offered relief from the heat, g In hindsight, Parpart blames herself for not ¡5 checking the Popsicle’s ingredients, which 5

DEMIC

included yogourt made with milk. A touch to the lips, and seconds later Bridget’s face was covered in hives. But the implications ^ of that relatively mild reaction were not I immediately apparent, and her parents réagi soned the red welts would fade, just as they ï had the first time. Bridget soon dozed off, and £ her father left to take home an antique dress| er the couple had just bought at a yard sale. ^ Parpart was alone with Bridget when the “ eight-month-old girl began to puff up so badly that her left eye swelled shut. Parpart g tried calling 911; her cellphone battery was 5 dead. She began to panic and yelled to pedesa trians for help. Someone phoned paramedics,

who were on the scene in minutes to inject Bridget with adrenalin. “What we wound up having was a complete medical emergency right there on the street.”

Bridget is now 3V2 years old and has grown into a theatrical, fun-loving child who is fond of The Little Mermaid, and whose parents are so very thankful—and fortunate—to still have her. There have been other scares, equally serious, and tests today show that in addition to dairy products, little Bridget is severely allergic to eggs and many nuts, including peanuts, almonds and cashews. She also suffers from the allergic form of asthma, which obliges her parents to administer an inhaled steroid twice a day to prevent the types of painful seizures that have hospitalized Bridget twice already in her young life.

Bridget’s case is just a tiny part of an unprecedented allergy epidemic in the Western world that puts the unrealized avian flu crisis to shame, and rivals obesity as a health problem. For some as yet elusive reason, the global incidence of allergic diseases such as food intolerances, asthma, eczema and hay fever is going through the roof in comparatively well-to-do Western cultures, says Mark Jackson, director of the University of Exeter’s Centre for Medical Ffistory in England, and author of the forthcoming bookAllergy: The History of a Modern Malady. There are only theories as to why this is so. The predominant notion holds that an overly hygienic Western lifestyle—marked by the availabili-

ty of everything from indoor plumbing to antibiotics—has left many of us with immune systems primed to overreact when they finally do stare down an “invader”: milk, for instance, or pollen. “If you go back to the beginning of the 20th century, the notion of allergy wasn’t even around,” Jackson says. “A hundred years later, we now think that between 20 and 30 per cent of the Western population is allergic to something—and the figures suggest, certainly in Europe, that perhaps 50 per cent of the population will have some kind of allergy by 2015.”

Almost 50 per cent of infants today suffer from some form of eczema, and the prevalence of hay fever stands at between 30 and 40 per cent of the population—a twoto threefold increase in the last few decades. (In 2003, 18.4 million American adults were diagnosed with hay fever, as were 6.7 million children in 2004.) Health Canada estimates that non-food allergies are “the most common chronic condition in Canadians 12 years of age and older.” The Allergy,o

Genes and Environment Network, or Allerm Gen, is Canada’s response to the crisis. Part ^ of the country’s Networks of Centres of Ex^

cellence, Hamilton-based AllerGen is comw

prised of more than 100 scientists at 20 uni^

versifies and research facilities across the ¡¡j country. Dr. Judah Denburg, AllerGen’s sci^ entific director, is unequivocal: “What’s at Z

stake,” he says, “is the possibility that—if we don’t either change how we live, or the way that our bodies and immune systems interact with the environment—we’re going to have a flurry of chronic diseases to deal with.” Children, who have been particularly hard hit, are proving to be the proverbial canary in the coal mine. In one study, Dr. Allan Becker at the University of Manitoba looked at 14,000 boys and girls born in 1995 and found that as many as 14 per cent had asthma. “We’re talking about one in seven children— that’s a huge proportion of the pediatric population,” Becker says. “It’s in every classroom,

every school, and many, many families. It’s huge.” This reality is reflected in the population at large. Asthma affects about three million people in this country, six out of 10 of whom do not have control of their disease, according to the Asthma Society of Canada. It kills 500 people in Canada each year, 5,000 in the U.S. Meanwhile, the World Health Organization says 150 million people around the world have asthma, and over 180,000 die annually as a result of it.

And that’s just one kind of allergic reaction. Denburg estimates that in the past two or so decades, the prevalence of food allergies has risen from less than one per cent of the population to as high as five per cent, depending on the study cited. Food allergies affect some 12 million Americans, resulting in more than 30,000 emergency room visits annually in the U.S., according to the Food Allergy & Anaphylaxis Network. It is estimated that between 150 and 200 Americans die annually from anaphylaxis as a result of food. Canadian figures are generally scarce. For anaphylaxis-related deaths, experts are obliged to extrapolate from the American figures, which suggest between 15 and 20 people die from the shock each year in this

country. That figure is likely much too low, the experts point out, noting they believe many cases go unreported.

The support group Anaphylaxis Canada says that, contrary to a popular misconception, the number of food allergy deaths has not gone up; it may even have declined slightly in recent years. But this, as Denburg notes, has everything to do with greater public awareness, and the fact that many people now carry their own EpiPen—an emergency shot of epinephrine, better known as adrenalin. A number of these injectors are stocked by hospitals, but many children own them. Last

year in Canada, 335,000 epinephrine injectors were sold, up 61 per cent from 208,000 purchased in 2001.

The consequences of not having ready access to an epinephrine injector have proven tragic, as the case of Sabrina Shannon illustrates. As with Bridget Wadden, Sabrina wasn’t yet a year old when she suffered her first severe allergic reaction to milk. For 13 years, Sabrina lived with the threat of deadly anaphylaxis, brought on by peanuts, soy and dairy products. “I felt so completely alone with Sabrina’s allergies,” her mother, Sara Shannon, told Maclean’s. Sabrina was 13 in September 2003 when she bought an order of french fries from her school’s cafeteria in Pembroke, Ont. In a little over an hour, she was dead. A coroner’s probe later suggested Sabrina suffered an anaphylactic episode brought on by trace amounts of cheese left on the tongs used to serve her fries, the same tongs that had been used to serve someone else poutine.

A bill dubbed Sabrina’s Law passed in Ontario last year now requires school boards to implement procedures to deal with lifethreatening allergies like Sabrina’s, which include training school staff to recognize the

symptoms of anaphylaxis. The law is the first of its kind in Canada. Most milk allergies are not life-threatening, but absolute numbers are not readily available. “It is not the most common presentation,” Becker says, “but it is certainly not rare—rare would be a bad adjective.”

All of this, of course, comes with its own price tag. Allergic diseases, Health Canada, estimates, cost the Canadian economy $15 billion in everything from emergency room visits to prescribed medications. Compounding the issue is the fact that we have far too few specialists: in 2003, there were only

126 practising physicians in immunology and allergy in Canada, compared with almost 1,000 cardiologists.

Any substance that triggers an allergic reaction is called an allergen: pollen, dust mites, pet dander, mould, food proteins or any one of a vast array of chemicals in the environment. When an allergen is ingested, inhaled or absorbed through the skin, it stimulates the production of an antibody called immunoglobulin E, or IgE. Subsequent exposure can elicit increasingly violent immune responses, as the body mistakenly marshals its resources to attack what should be, by all rights, a harmless substance. Much depends on previous exposure, and just how much allergen the person comes into contact with.

Some IgE antibodies bind to the surface of mast cells, which line the skin, nose, intestines and bronchial tubes, and play a role in fighting parasitic infections. Mast cells also course through the blood. When an allergen enters the body, it binds to the IgE antibody on the surface of these mast cells, and sparks the release of a chemical torrent flush with histamine and prostaglandins, among other

immunologically active molecules. This flash flood leads to itching, inflammation, mucus production, bronchial constriction, coughing and wheezing. Tissue damage can be the final extreme outcome.

Anaphylactic shock is the worse-case scenario—a massive attack on the skin, and respiratory, gastrointestinal and cardiovascular systems. It can be marked by swelling, laboured breathing, circulatory collapse, and sudden death. While food is the most common cause, it can be brought on by insect stings, medicine, latex, even exercise. It is usually diagnosed in childhood, but can develop in adults, too. Its impact isn’t always sudden, as Bridget Wadden’s experience illustrates. Among those at risk for anaphylactic shock, about one in five (like Bridget) have attacks that occur in two phases: one relatively mild, the second life-threatening, anywhere between one and eight hours after the first. According to Anaphylaxis Canada, one to two per cent of Canadians live with the prospect of keeling over without warning due to anaphylactic shock. More than 50 per cent of the population knows someone at risk.

In some cases, people grow out of their allergies. In others, it only gets worse. Chil-

dren with an allergy to either milk or eggs have been shown to sometimes lose their sensitivity to the offending substance over time. That’s usually not the case with nuts and seafood, though the thinking here is still evolving.

Our best educated guess at why we get allergies in the first place is known as the hygiene hypothesis. It’s widely credited to British epidemiologist David Strachan, who in the British Medical Journal in 1989 suggested that clean living isn’t necessarily good for us. By depriving our immune system of key infections caused by viruses, bacteria and par-

asites, we fail to develop the necessary tolerance for ordinarily tame foreign particles. In short, the immune system—underused and spoiling for a fight—goes ballistic when finally given the opportunity, no matter how slight the opponent.

Denburg at AllerGen suggests credit for the hypothesis should properly go to University of Saskatchewan professor Dr. John Gerrard, who planted the germ of the theory in research he published in the Annals of Allergy in 1976. Gerrard studied IgE antibody levels in the blood of whites and Metis in Saskatchewan and suggested that a higher incidence of allergies among Caucasians was “the price paid by some members of the white community for their relative freedom from diseases due to viruses, bacteria, and [parasitic worms].”

Support for the hygiene hypothesis comes from several quarters. Poor people living in developing countries, where a viper’s nest of infectious diseases still afflicts the population, exhibit a markedly lower inclination toward developing allergies. This holds true even for impoverished communities within polluted urban centres. Supporting evidence comes from a German study of Bavarian

farmers, whose stables typically adjoin the farmhouse, says Denburg. It turns out that the children of those who made a living off the land had fewer allergies than did Bavarians who did not farm.

Dirt, in other words, may be good for you. In a similar vein, having a dog in the home from the first day a child arrives has been linked in some studies to a reduced risk of allergy. Multiple siblings who bounce childhood infections off each other also help, as does eating good bacteria known as probiotics, found in, for example, yogourt with live bacterial cultures. Breastfeeding remains

controversial, Denburg says. Some resean has shown it does not protect against allei gies, as has been suggested.

There appears to be such a thing as good dirt and bad dirt. Research indicates that persistent exposure to particulate matter due to automobile exhaust in urban settings increases the risks of developing allergies and exacerbates asthma. Japan is a classic example of industrialization’s downside. In the 1930s, hay fever hadn’t yet been recognized as a condition in Japan, notes Jackson, the author of Allergy. However, by the 1960s and ’70s, 15 per cent of Japanese schoolchildren were showing signs of hay fever. “So, in the space of a very short period of time, during which Japan underwent rapid industrialization,” Jackson says, “the incidence of hay fever skyrocketed.”

Other studies suggest that exposure to antibiotics may be to blame. The timelines certainly dovetail: over the past 40 years, as widespread antibiotic use has climbed exponentially, so, too, have allergy rates. But it’s more than just guilt by association. In findings presented to the European Respiratory Society in Vienna in 2003, researchers noted that, in a study of 448 children, in-

fants prescribed antibiotics within the first six months of their lives ran 2.5 times the risk of developing asthma as infants who didn’t take antibiotics.

A year later, at a meeting of the American Society for Microbiology, scientists attempted to explain why this might be the case. Their study of mice treated with antibiotics provided a possible explanation for the rising incidence in asthma and allergies. They noted that antibiotics cause changes to the microbe population in the gastrointestinal tract that may be linked to how the immune system responds to commonly inhaled allergens.

“We all have a unique microbial fingerprint— a specific mix of bacteria and fungi living in our stomach and intestines,” Gary Huffnagle, one of the authors, and an associate professor of microbiology and immunology at the University of Michigan, said at the time. “Antibiotics knock out bacteria in the gut, allowing fungi to take over temporarily until the bacteria grow back after the antibiotics are stopped. Our research indicates that

DIRT IS GOOD-BAVARIAN FARMERS LIVING NEXT TO THEIR HORSES WERE MUCH HEALTHIER

altering intestinal microflora this way can lead to changes in the entire immune system, which may produce symptoms elsewhere in the body.”

In essence, with the gut’s bacteria decimated by antibiotics, fungi are free to grow and secrete oxylipins, a common group of chemicals found in mammals, some of which are key to modulating the immune response. The fungal oxylipins block production of the immune system’s T cells that would normally handle swallowed allergens. Their absence in the gastrointestinal tract leads to a hyperactivity of T cells in the lungs in the presence of, for example, ordinary pollen or some other allergen. In other words, a single action may set off a domino effect with lasting influence.

Whatever the cause, it doesn’t much matter to Tony D’Agnone, who is allergic to his work. Actually, it makes the 58-year-old Alberta farmer deathly ill. It wasn’t always that way. Thirty years ago, hauling grain caused only minor respiratory discomfort, similar to what D’Agnone experienced as a boy with hay fever. But it’s a dirty job, and over the years D’Agnone’s health worsened. To load his truck, he’d shovel the grain into an auger, which spewed swirling clouds of grain dust into the stagnant air inside the cramped storage bin on his farm in Skiff, about 100 km southeast of Lethbridge. By the time the mid-’90s rolled around, a day’s hauling would leave the father of three shaking all over, arms aching. He could barely eat supper, and was routinely popping Tylenols and antihistamines. He was getting desperate. “Either I’d have to change my occupation,” D’Agnone recalls thinking, “or else I’d have to get my grain custom-hauled, and there’s hardly any money in agriculture as it is.” While growing up on a farm typically seems to lessen the odds of developing allergies, it is no guarantee, as D’Agnone’s case shows. Through an acquaintance, his wife learned about a possible lifeline. The Kasco dust helmet looks like something a motorcyclist

would wear, only with two large filtered ports above and behind each ear. It features two small whirring motors powered by 12-volt rechargeable batteries. The helmet seemed to be just the thing, but the D’Agnones balked at the $1,100 price tag. Then, in 2002, the harvest was wet, and there was a lot of mould in the grain. The job of hauling was never worse. “I got so sick, I almost had to be hospitalized— it knocked me down for three days,” D’Agnone

recalls. “That’s when we broke down and bought the helmet—it was a lifesaver.”

But walking around with a crash helmet on isn’t an option, or necessary, for most people for whom medical relief comes from the seasonal march to the drugstore. Last year, pharmacies and hospitals stocked their shelves to the tune of $105 million in over-the-counter medicines (the Reactines and Claritins of the world) and prescription-based antihistamines— up 15 per cent over 2001, says IMS Health. Not surprisingly, the lucrative trade continues to attract new entrants, including Nasaleze, an ironic twist on pollen-allergy relief that is formulated from cellulose found in plant stems. A fine powder spray, Nasaleze has no pharmacological activity, and simply coats the nasal passage, forming a sticky trap for pollen, says Peter Josling, a spokesman for the company. Instead of battling the symptoms with the likes of antihistamines,

Nasaleze is said to stop the offending allergen from entering the lungs in the first place. A handful of small trials suggests it works in helping to filter the 20 billion particles many of us breath in daily. “This is the only white powder,” Josling jokes, “that you can legitimately put up your nose.”

More powerful prescription medications for severe asthma sufferers include drugs like Xolair. First sold in the U.S. in 2003, Xolair saw its sales last year go up 71 per cent, hitting US$321 million. Some analysts expect demand to soon push annual sales as high as US$1 billion. The injectable drug, which was approved for use in Canada a little over a year ago, works like a sponge, mopping up the body’s IgE mess. About 50,000 patients are on Xolair in North America, says Jason Jacobs, a spokesman for Novartis Pharmaceuticals Canada. But at $600 a vial, it’s not cheap.

Depending on the patient’s weight and the amount of IgE in the body, a year of treatment can run anywhere from $7,000 to $43,000. On the other hand, says Jacobs, “it significantly reduces severe attacks and hospitalizations in the toughest-to-treat patients.”

Research now under way at AllerGen is looking to push the boundaries of allergy treatments. Scientists, armed with an in-

creasingly intimate knowledge of how our immune system functions, are chopping up various allergens into their tiniest molecular components. The goal is to introduce these fragments into allergic individuals so that, unlike traditional allergy shots, they actually pull the plug on the allergic reaction itself. “We now have a lot more knowledge about the genetics and the molecular biology of the immune system to switch these things off,” Denburg says.

AllerGen has also corailed an impressive pack of immunologists, epidemiologists, asthma specialists, geneticists and others to collect data from what its researchers are calling the “birth cohort”— a group of10,000 families that they hope will be involved in the largest study of its kind in the world. The goal is to observe pregnant women soon after they conceive and then follow their children for as long as possible, perhaps into adulthood, if funding allows. They can then examine as many aspects of the families’ environments as possible to deter-

mine why, and in what circumstances, people may develop allergies.

Food allergy sufferers show some of the most extreme symptoms, which necessitates meticulous attention to proper food labelling. Canada has nine so-called “priority food allergens” that manufacturers are required to name. This list covers the usual suspects— peanuts, tree nuts (meaning almost all other nuts, such as almonds, pistachios and walnuts), wheat, milk, eggs and fish (which includes crustaceans, such as crab, as well as shellfish)—but also some more unusual ones: soy, sesame seeds, and sulphites, which are used as preservatives.

As well-intentioned efforts to sanitize the world spread, we do a lot of good, but they may result in unintended consequences as well. Denburg, for instance, cites the Bill and Melinda Gates Foundation, which has done much-needed humanitarian work in developing nations to combat infectious diseases. Since its inception, the foundation has dedi-

cated US$1.4 billion toward the cause. But the Catch-22 is that by cleaning up the developing world’s environment-much as we have done in the Western world— we may in fact be exporting our predisposition for allergies and asthma. No one is suggesting the aid stop, but the answer may require the medical community to think more strategically about how to go about easing the burden of disease. “What I really think we need to do,” Denburg says, “is not have blockbuster programs to eradicate everything and then say that that’s great.” As the world of science grapples with the maddening complexities, individuals and their families wrenched by severe allergies are forced to find ways to cope without the everyday things in life so many of us take for granted: finding suitable daycare, a school that meets with our standards, and a normal social life for our kids. Parpart says a dozen daycare centres have turned down Bridget. “No one wants to be in charge of a child who could die if they feed her the wrong thing.”

There are days Parpart has never felt better. “Other days, you might as well put me on Wellbutrin,” she says. “You just get depressed because you realize you don’t have the same options that other parents have.” It hasn’t been easy getting friends and family to fully understand just how bad it can get for Bridget, and just how little it takes to push her over the edge. A trace of milk here, a bit of peanut butter there. “It clarifies who your friends are. You learn who you can trust,” Parpart says. “You figure out who’s detail-oriented enough to cook for you and your child, and you make that your new family.” And you hold on to your trustworthy friends—and your children—“like they mean everything to you.” Which, of course, they do. M

Cathy Gulli

Nicholas Köhler