We're far too clean for our children's comfort

By MARTIN JOHNSTON

The answer to asthma could lie on the carefully wiped tables and scrubbed benches of the ordinary New Zealand home.

Paradoxically, many scientists believe the problem is not hidden germs, as most of us would suspect. More likely, they say, it is the lack of them.

The average Western home is a lot cleaner than it was 100 years ago, with thoroughly treated tap water, chemically preserved food and disinfectant cleaners killing germs in kitchens and bathrooms.

As a result many children - unlike their great-grandparents - grow up without fighting a constant battle against bacterial diseases.

Now a growing number of researchers are exploring the theory that this ruthless suppression of bugs may have contributed to growing rates of asthma, the lung disease suffered by one in six New Zealanders and ranked as our third worst disease (behind depression and anxiety disorders) for its effect on quality of life.

The so-called hygiene hypothesis argues that the body's immune system, free of the need to fight bacteria, overreacts to imagined threats from household dust mites and other sources.

However, scientists emphasise it is still only a theory and admit that many aspects of the disease remain a mystery.

Leading asthma researcher Professor Richard Beasley, director of the Medical Research Institute, said two years ago that our knowledge of asthma compared with that of cancer, stroke and heart disease in 1970.

Now Beasley says there has been progress, "but it's fair to say that our current understanding of asthma does not explain the international patterns".

What triggers asthma?

Asthma is defined as breathing difficulties - wheezing, coughing, breathlessness or chest tightness - caused by inflammation of over-sensitive breathing tubes in the lungs. A wide range of triggers, which worsen the inflammation, muscle spasms and mucus, have been identified.

Doctors and nurses advise asthma sufferers to identify and then avoid, if possible, their own triggers, which can include allergens - things that provoke an allergic reaction in asthmatics. Other possible triggers are tobacco smoke, dust, fumes, colds, weather changes and some foods and drugs (including aspirin).

Exercise can be a trigger for some people, but rather than give it up they are advised to modify it or find other ways of minimising their symptoms.

What are asthmatics allergic to?

Between 70 and 80 per cent of asthma cases in New Zealand are linked to allergies. The most common asthma-producing allergens are house dust mite faeces, cats' hair and saliva, pollen, urine from rodents, and mould.

Wellington Medical School researchers found some of the world's highest levels of the main dust mite allergen in the city's homes and have suggested that the removal of fitted carpets is one way of reducing them.

They have also shown that synthetic bed duvets - long recommended for asthmatics - contain 15 times more of this allergen than feather quilts. This is probably because the highly popular man-made product's outer fabric is of a looser weave.

The finding led to the withdrawal of the longstanding recommendation of synthetic duvets for asthmatics. The researchers suggest using special covers for bedding to contain the mites' microscopic faeces. Other recommendations include keeping pets outside, making sure the home is warm and dry (to avoid mould) and regularly cleaning surfaces where the mite grows.

But is cleanliness the answer - or the problem?

Some scientists think the rise in allergy-linked diseases, including asthma, eczema and hay fever, may be caused by lower rates of childhood infection over the past century as medical treatments and hygiene standards, such as safer food and water, have improved.

"People are asking the question: have all those things together conspired to cause the immune system as it develops in infants and young children to change," says Julian Crane, professor of clinical epidemiology at the Wellington Medical School.

Some researchers are also applying the theory to other immune disorders, such as type 1 diabetes, he says.

But the so-called hygiene hypothesis remains a theory. Much of the evidence is contradictory and researchers stress they are not advocating a return to unhygienic conditions and high rates of childhood infectious diseases which are themselves major causes of sickness and death.

How could better hygiene be responsible for asthma?

Crane explains that part of the immune system is devoted to fighting bacteria and viruses with Th1 cells, while the other part is designed to attack worms with Th2 cells. One side or the other is dominant.

Researchers speculate that if the first side is underused, the second may become overproductive and attack imaginary threats to the body.

Crane notes that the worm-killing side produces a protein called IgE, which is found at high levels in asthma sufferers with dust mite or pollen allergies. Researchers have found that children in developing countries also have high levels of IgE but little allergic disease.

They suspect this is because their bodies need the protein to fight worm-based diseases. But in Western countries without the same diseases, the overproduced protein may end up fighting harmless substances such as dust mite faeces or pollen.

Does our genetic make-up play a role in asthma?

Yes, in the sense that the disease tends to run in families. But environmental factors seem more important in deciding whether asthma becomes a problem, as a large international study has found.

Since 1991, researchers in 56 countries have been measuring asthma prevalence among 721,000 children aged 6-7 or 13-14 in a study called Isaac, the International Study of Asthma and Allergies in Childhood.

The key marker was having wheezing or whistling in the chest in the previous 12 months.

Among 13-14-year-olds, they found rates of 20 per cent or higher in New Zealand, Australia, Britain, Canada, the United States and parts of Central and South America. The chairwoman of the Isaac steering committee, Associate Professor Innes Asher, of the Auckland Medical School, says one of the ongoing study's surprising findings is that some people of similar genetic stock, but living in different places, had markedly different childhood asthma rates.

Hong Kong's rate was 20 per cent, while in Guangzhou it was less than 5 per cent.

Portugal had intermediate rates, while in Portuguese-colonised Brazil there were some high rates.

"This evidence suggested strongly to us that the main reasons for variations in rates of asthma around the world were due to environmental influences, not genetic influences," says Asher.

In New Zealand, Maori and Pacific Island children have the same rates of asthma but higher hospitalisation rates. Researchers believe the difference lies in access to health care, rather than biology.

What are the likely causes of asthma?

The study checked for links between asthma rates and a number of environmental and social markers and unearthed fresh evidence for the hygiene hypothesis and other theories. It found:

* The richest countries on average wheeze at twice the rate of the poorest.

* The higher a country's notified rate of tuberculosis, the lower its rate of asthma.

* No link between overall asthma and national immunisation rates, although among the older children immunisation was potentially protective against asthma.

* No significant link between asthma and eating fats, but a hint of increased risk from eating "trans fatty acids", present in margarine and many other foods. The more seafood and olive oil children ate, the lower their asthma risk, but it was only a weak association.

* Higher vegetable consumption was linked weakly with lower asthma rates.

* Eating cereals and nuts was more noticeably protective.

Smoking is a known asthma trigger, but the Isaac findings discount it as an explanation for countries' different asthma prevalence rates. Pollen and pollution are also triggers, but this study failed to find significant links to prevalence of the disease.

Will the study lead to new asthma drugs?

Many international studies are looking for drugs to treat the immune systems of people with allergies or to vaccinate children to stop them becoming allergic.

In New Zealand there are two main streams of research. One involves the use of the tuberculosis vaccine BCG, derived from a weakened strain of cattle tuberculosis bug. The trials have had mixed results. An initial study led by Beasley testing repeated injections in humans produced unwanted side-effects, including localised swelling.

"The other finding was that we were unable to show an effect in terms of asthma control," says Beasley. "It's these sorts of studies that have led to groups like Genesis attempting intra-nasal administration."

Genesis Research and Development, a New Zealand-based biotechnology company and its British partner SR Pharma say they are working on a nasal spray to deliver their experimental asthma vaccine, Avac, more thoroughly to patients' upper airways.

A preliminary trial to test safety using nasal drops was successful, Genesis says. Symptoms were not reduced, but this was expected as they continued on their asthma drugs and the drops were not expected to spread the vaccine well through the airways.

Wellington's Malaghan Institute of Medical Research is continuing its animal-based research with the BCG vaccine, trying to find a part of it to use that is effective but spares patients the side-effects. It says it has identified the key molecules produced by BCG that could lead to a safe and active vaccine.

Its asthma group leader, Professor Graham Le Gros, is excited about the potential of some genetically modified "glow-in-the-dark" mice, which provoked protests from anti-GM campaigners when they arrived two years ago. Le Gros says a green fluorescent jellyfish protein replaces a hormone made by Th2 cells from the worm-killing side of the immune system. When the cell starts producing an allergy, the cell lights up inside the mouse.

What else is being done here?

The other main local research effort focuses on pills containing lactobacilli, beneficial bugs found in yoghurt. Trials of these bugs, called probiotics, will test whether they reduce symptoms of eczema and hay fever, which often occur alongside asthma. A preliminary study of probiotics in Europe has shown a reduction in babies' eczema.

Studies have suggested that lactobacilli are less common in the gut of Westerners than in people from the Third World, and less common in children with allergies than those without.

Crane says the aim is to test if manipulating the makeup of the bowel's bacteria can change early development of the children's immune systems away from the allergic response.

Part of the research base to the probiotics theory is the strong suggestion from European and New Zealand studies that the use of antibiotics in early life is linked to asthma and other allergic diseases later on.

Crane's team is also involved in an asthma study of more than 1000 urban children followed since birth, looking at factors including maternal and infant diet, infections, immunisation, passive smoking and indoor allergens.

Are farm children less likely to develop asthma?

Professor Neil Pearce, the director of Massey University's Wellington-based public health research centre, says European studies have revealed, but not explained, a protective effect on their farms.

"It seems to be livestock - cattle basically.

"European farming has a lot more contact between humans and animals. The animals are often kept indoors, so New Zealand is a good place to test the theory because there's less contact here."

His centre will start a three-year study in the lower North Island next month, comparing 3000 families who live on farms with 1000 in cities and towns.

How far away is a breakthrough asthma drug?

Crane says a dozen or more molecules have excited drug companies and of them one or two might become potent weapons.

nzherald.co.nz/health