By LOUISE THOMAS

Asthma is not giving up its secrets easily.

A global study of childhood asthma and allergies involving more than 700,000 children in 155 centres across 56 countries has netted results that present medical thinking is at a loss to explain.

Researchers are finding striking differences in the prevalence of asthma in different countries. (After Britain, New Zealand is the second wheeziest nation in the world.)

The first phase of the study has produced a world map of asthma and allergy occurrence. The results challenge present theories about the cause of asthma.

Phase two is just beginning for researchers across the world, including Otago University's Wellington Asthma Research Group. New Zealand, with its high incidence, is of special interest to the international research team. Other top scorers besides Britain are Australia and Ireland, followed by North, Central and South American countries.

Countries like those in Eastern Europe and Indonesia, Greece, China, Taiwan, Uzbekistan, India and Ethiopia are relatively asthma-free.

A previous theory that genetics played a major role in global asthma patterns has been discredited by the study.

Professor Richard Beasley of Wellington, coordinator of Phase One of the International Study of Asthma and Allergies in Childhood (Isaac), says that while genetics is still important on an individual basis (an asthma sufferer still needs the right genetics for the expression of the disease), there is no correlation between genetic types and occurrence.

Hong Kong has a prevalence rate five times higher than Guangzhou, he says. "These two places are very close geographically and the two peoples have a similar genetic background."

European people who had migrated to Australia showed marked differences from those in Europe. So the evidence suggests that environmental factors, whatever they are, are more powerful than genetic makeup.

"Air pollution has always been widely regarded as a risk factor but I think this study clearly shows that this doesn't play a major role.

"For example, New Zealand has one of the highest asthma prevalence rates but little air pollution.

"Smoking is regarded as a risk factor, but it certainly does not have a major influence on these patterns - this is not a global pattern of cigarette consumption.

"So we know about risk factors at an individual level, but clearly we don't fully understand the role of other major risk factors that are producing such striking differences in asthma prevalence."

Professor Beasley says phase two will involve the testing of different theories of the possible causes of asthma in an attempt to explain the global trends.

The first-phase study saw patterns that were completely unknown before.

For example, there was a very strong gradient of asthma incidence across Europe, from the northwest to the southeast. There were 10-fold differences between Britain and Greece.

The study will now look at a smaller number of selected centres in much greater detail and the possible risk factors involved in asthma and allergies, to see if a start can be made to explaining such trends.

"There are very few diseases where we cannot explain global patterns," he says.

"I think we are in the same position with asthma as we were with cancer and cardiovascular epidemiology of 30 years ago."

Still to be examined is the relationship between early life diseases of children and asthma.

In particular, researchers are interested in any respiratory infections children may have previously suffered.

Some researchers believe that some types of respiratory infections in childhood may be protective and other types of infection may predispose you towards asthma.

For example, there is an inverse relationship between tuberculosis rates and asthma prevalence. So the centres that had very high rates of tuberculosis had a corresponding low rate of asthma.

"Is TB in some way protective? This is an interesting possibility, as there is evidence that if your lung develops an immune system to fight TB, then it doesn't become allergic, a condition necessary for asthma," the professor says.

Major funding for the Isaac project has come from the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, and Glaxo Wellcome International.