A new theory about what really causes allergies promises to revolutionize how they're treated in the future.

By Rochelle Green

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Ask any doctor for the most important medical advances of the past century and among the answers will be public health victories such as indoor plumbing and improved sanitation. We've all enlisted in the war against germs, brandishing disinfectant sprays and antibacterial soaps. But some specialists are beginning to think that our squeaky-clean lifestyle may be breeding an alarming increase in the number of children with allergies.

"It may be that exposure to bacteria and other infectious agents early in life is a good thing," suggests Robert A. Wood, M.D., an associate professor of pediatrics at the Johns Hopkins University School of Medicine in Baltimore. "It's possible that it focuses your immune system on fighting microbes and directs it away from mounting allergic attacks against harmless pollens and other environmental debris."

This theory, known among scientists as the Hygiene Hypothesis, is revolutionizing the world of allergy research. It may explain why respiratory allergies are nearing epidemic levels in developed countries. And it has inspired innovative research that has the potential to produce a new approach to treatment.

As many as 40% of children in the U.S. have allergic rhinitis, the condition that brings on nasal congestion, sneezing, and a runny, itchy nose. Some kids suffer seasonally from spring-to-fall plant pollens. Even more are affected year-round by indoor dust mites, mold spores, animal dander, and cockroach allergens. Each year, allergy symptoms and complications cause children to miss 2 million days of school, according to a recent task-force report by leading allergy organizations. Many children with allergies go on to develop asthma, an inflammation of the lungs that causes breathing difficulties.

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The idea that cleanliness might be the culprit has only slowly taken hold. In 1990, the year of Germany's historic reunification, Munich pediatrician Erika von Mutius, M.D., was surprised to find that allergic disease was far less common among children in polluted Leipzig, in East Germany, than in cleaner West German cities. Over the next few years, as the former East Germans lived more like the Westerners, their rates of allergy shot up. These findings are in keeping with other regional comparisons, which show that allergy and asthma are more common in children in such countries as Britain and Australia and less common among children in China, Indonesia, and Ethiopia.

Other studies point to protective factors. Last summer, researchers at the University of Arizona College of Medicine in Tucson reported that infants who attended daycare or had older siblings at home were less likely to experience asthma or to suffer from frequent wheezing later in childhood. This, researchers say, is possibly due to increased exposure to infection.

The Dirt-Allergy Link

What does a dose of dirt have to do with developing allergies? Our immune system's T cells have two major pathways to defend against foreign invaders. One type of cell, Th1, creates killer T cells and certain antibodies that destroy disease-causing agents like bacteria while leaving normal body cells intact. Th2 cells, on the other hand, unleash different antibodies that can cause allergic responses, even to harmless allergens.

The Th1 path is inactive during pregnancy, probably to prevent the fetal immune system from rejecting the mother, explains Arthur M. Krieg, M.D., professor of internal medicine at the University of Iowa in Iowa City. After birth, exposure to bacteria and other germs normally strengthens the Th1 path. "But parents today are vigilant about germ protection," he says. "There's less stimulus for a child's immune systems to develop in the direction of Th1." According to the Hygiene Hypothesis, that leaves the balance in favor of Th2, predisposing a child to allergy.

Although intriguing, this theory offers little in the way of practical advice for parents. Scientists are not yet able to pinpoint exactly which bacteria are the ones our bodies should be exposed to. As Dr. Krieg notes, "There are many types of bacteria. We can't just say that they're all good and send our children to play in the dirt." In fact, house dust is more likely to contain allergens and should be kept to a minimum if your child has indoor allergies.

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An Allergy Vaccine?

The real importance of the Hygiene Hypothesis is the fact that it proposes a new way to design treatment that may someday actually prevent allergy. And those research efforts are already under way. Scientists led by Eyal Raz, M.D., an associate professor of medicine at the University of California, San Diego, have sensitized mice to ragweed, priming their immune systems to throw an allergic tantrum in the presence of ragweed pollen. Over several weeks, the mice are immunized against ragweed with an experimental vaccine, then taken to a small breathing chamber and hit with a puff of pollen. Small sensors in the walls detect how well the mice can breathe -- a measure of how well the vaccine works.

Across the country, at the Johns Hopkins Asthma and Allergy Center, researchers are examining adults with ragweed allergies in both skin-testing and allergy-shot studies to compare the safety and effectiveness of the experimental vaccine with an inactive placebo. The vaccine resembles immunotherapy, better known as allergy shots -- an approach that teaches the body to tolerate ragweed and other allergens through increasing exposure. But in the case of the new vaccine now being tested, the ragweed allergen has a surprising partner: a bit of DNA that is unique to bacteria and other microbes.

In theory, the presence of the bacterial DNA should alert the immune system that there's an infection requiring a protective response, says Dr. Krieg, who started working on the question at the National Institutes of Health in Bethesda, MD, and has since formed a company to investigate and create an allergy vaccine. "Giving DNA along with ragweed allergen tells the body that ragweed is part of an infection."

So far, the strategy appears to be working. Dr. Raz's sensitized and immunized mice had no trouble breathing when challenged with ragweed allergen. Dissection revealed evidence that their immune function had changed from an allergic to a protective response. But while mice are useful in research because their genetic makeup can be easily controlled, their response doesn't necessarily predict what will happen in the human body.

Last year, a skin-test study at Johns Hopkins showed that the DNA-ragweed vaccine caused much less of a reaction on the arms of allergic subjects. With the study currently taking place, in which people are now receiving actual shots, researchers will be looking to see whether injections of the material also stimulate a strong protective response, the way they do in mice.

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The Best Allergy Medicines

It may be years before the vaccine's true potential is known. But with recent advances in drug therapy, doctors can tailor treatment to a child's symptoms. "Nearly 100% of children can be effectively treated with drugs or allergy shots," says William Dolen, M.D., professor of pediatrics and medicine at the Medical College of Georgia in Augusta. Here, the best options:

Prescription nasal steroid sprays such as Flonase and Nasonex are considered the gold standard in allergy treatment because they reduce nasal swelling, the most troublesome symptom. Available for kids as young as 3, the once-a-day sprays deliver a far lower dose than steroids given by mouth or injection, so they have fewer side effects. A nonsteroidal spray, NasalCrom, is available without a prescription for children ages 6 and older. It can reduce milder nasal swelling but has to be taken three to four times a day.

Antihistamines relieve sneezing, itching, and runny noses. Prescription antihistamines (such as Claritin and Zyrtec), given just once a day, are safe for children as young as 2. Astelin Nasal Spray is an antihistamine that also treats nasal congestion, though some people complain of sleepiness and a bitter taste. You should avoid over-the-counter antihistamines such as Chlor-Trimeton and Benadryl, which can affect your child's cognitive skills.

Decongestants relieve nasal swelling, but only mildly. They're available in OTC formulas, such as Sudafed, for children as young as 2, and are also added to prescription antihistamines, like Claritin-D. Antihistamine and anti-inflammatory eyedrops, available without a prescription, safely relieve redness and itching, major symptoms of seasonal allergies.

Allergy shots (immunotherapy) may help children who continue to have symptoms despite medication. Extracts of specific allergens are injected in gradually increasing amounts to build tolerance to those allergens. The buildup phase requires one to two injections a week for about four months. Once the maintenance dose is reached, injections continue every two to three weeks for four to five years. Some children get significant relief from allergy shots and can give up medications, while others are only mildly helped. The shots are always administered in a doctor's office because of the small but potentially life-threatening risk of a serious allergic reaction, including anaphylaxis.

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What the Future Holds

With allergy rates on the rise, researchers are beginning to take a hard look at prevention, particularly for children at risk because of family history. Several ongoing studies, including one of more than 500 high-risk infants taking place in both Winnipeg and Vancouver, Canada, may soon tell us whether reducing exposure to dust mites and other allergens can keep a young child from becoming allergic or prevent an allergic child from developing asthma. Other research is looking at the early use of allergy shots and medications to ward off disease in asthma-prone kids.

If it turns out that we can't keep our children from starting down the allergy path, erecting a reliable roadblock may be the next best thing. Of all the advances in allergy treatment, only immunotherapy -- developed in 1911 -- has come close to rebuffing the allergic response. Now, the bacterial DNA vaccine being studied at Johns Hopkins and elsewhere may come even closer.

Peter S. Creticos, M.D., clinical director of clinical immunology at the Hopkins medical school, is the principal investigator of the vaccine's clinical trials there and is excited by the tremendous promise it shows. "All of the work up to now is encouraging," says Dr. Creticos. "The vaccine may prove to be safer; that is, less likely than conventional allergy shots to cause an allergic reaction. If it proves to be as potent in producing a protective response, we really do have a winner. And if the vaccine turns the disease off, we're talking about a potential cure."

Keeping Symptoms At Bay

There's plenty you can do right now to relieve your child's allergy miseries, whether seasonal or year-round. At the top of your list should be avoidance: routing dust mites and other allergens from your house and keeping seasonal pollens at arm's length. Limiting your child's exposure may take some effort, but it can markedly reduce symptoms and minimize the need for drugs.

If outdoor allergens are a problem, keep doors and windows closed during allergy season and run an air conditioner with closed vents (in the car too). Wash your child's hair each night to get rid of sticky pollens. Keep her away from lawn-mowing and leaf-blowing, activities that launch mold spores. And consider limiting outdoor play on dry, windy days, when pollen counts are highest.

Tackling indoor allergens can seem overwhelming. A mattress, for instance, can contain tens of thousands of dust mites. But there are reasonable strategies for gaining the upper hand: Cover pillows and mattresses in special encasements that mites can't travel through; wash bed linens every week in 130°F water, and keep them in the dryer for an hour; and use a double-layer vacuum bag to prevent the machine from leaking the mites back out.

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