The allergy epidemic

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June 05, 2006

The allergy epidemic

Macleans - Toronto,ON,Canada

http://www.macleans.ca/topstories/health/article.jsp?

content=20060605_128132_128132

Hay fever, asthma, eczema, peanuts. Millions are afflicted -- and

it's about to get much worse

DANYLO HAWALESHKA with Gulli and Köhler

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 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 nonchalant, " she recalls. He said not

to worry, it happens, just avoid dairy products. " We'd really been

given no indication of how serious this could be, " Parpart says. " I

didn't know that anyone could be life-threateningly allergic to

milk. "

Three months later, she and her husband 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. In hindsight, Parpart blames herself for not checking

the Popsicle's ingredients, which 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 immediately apparent, and her parents reasoned the red welts

would fade, just as they had the first time. Bridget soon dozed off,

and her father left to take home an antique dresser 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 tried calling 911; her cellphone battery was

dead. She began to panic and yelled to pedestrians 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 3 1/2 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

, director of the University of Exeter's Centre for Medical

History in England, and author of the forthcoming book Allergy: 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 availability 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, "

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 two- to 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,

Genes and Environment Network, or AllerGen, is Canada's response to

the crisis. Part of the country's Networks of Centres of Excellence,

Hamilton-based AllerGen is comprised of more than 100 scientists at

20 universities and research facilities across the country. Dr.

Judah Denburg, AllerGen's scientific director, is

unequivocal: " What's at 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

illustrates. As with Bridget Wadden, wasn't yet a year old

when she suffered her first severe allergic reaction to milk. For 13

years, lived with the threat of deadly anaphylaxis, brought

on by peanuts, soy and dairy products. " I felt so completely alone

with 's allergies, " her mother, Sara , told Maclean's.

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

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 's Law passed in Ontario last year now requires

school boards to implement procedures to deal with life-threatening

allergies like '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. Children 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 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 parasites, 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.

Gerrard, who planted the germ of the theory in research he published

in the ls 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 research has shown it does not protect against

allergies, 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 ,

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, " 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, infants

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, " 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 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 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 s, 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 s, " 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 increasingly

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 coralled 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 of 10,000 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 determine 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 dedicated 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.

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