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The prestigious journal Nature Medicine has published a UWA study proposing a radical new blueprint for the control of asthma in children - and Raine Study participants played a role in the international research.

Back in 1980, UWA Postdoctoral Fellow Pat Holt embarked on what has become a protracted journey to unravel the mechanisms of asthma, a disease that is expected to be the most common emergency bringing distressed parents and children to local hospitals this winter.

During the 1980s, asthma research around the world was accelerating as a result of what was becoming known internationally as ‘the asthma epidemic'.

"For several years people simply didn't accept what was happening, but as the incidence of asthma rose relentlessly, it was universally acknowledged that a First World epidemic was occurring. At that stage it appeared very much a ‘western-lifestyle-type' disease, for asthma was much less frequent in the Third World," recalls the UWA Adjunct Professor whose latest research findings (in collaboration with Professor Peter Sly who has recently relocated to University of Queensland) were published in the prestigious journal Nature Medicine.

Pat Holt's postdoctoral research back in 1980 provided the ‘eureka moment' that set him on his current research path. That involved developing an experimental model in which mice inhaled low levels of allergens to induce antibodies equivalent to those that cause the narrowing of airways in asthmatic humans. The aim was to identify the controlmechanism responsible for regulating production of these allergic antibodies, and ultimately to discover why this malfunctioned in asthmatics.

"The surprise was that not only did the mice fail to develop these antibodies, but instead the longer we exposed them the more resistant they became to allergic sensitisation. They had developed a state of profound immunological tolerance to the allergen that specifically prevented them making these antibodies. This tolerance phenomenon had never previously been observed in the lung, and we realised that it provided a major clue to how respiratory allergies are normally avoided by the healthy immune system," explains the UWA researcher.

"The challenge then became finding out what causes this immunological tolerance to fail in some humans, particularly during childhood when most asthma-associated allergies first manifest. I've been following that path of research ever since".

Professor Holt, Deputy Director at the Telethon Institute of Child Health Research, says the study - published in the biomedical journal Nature Medicine, Volume 18 (Number 5) May 2012 - brings together research spanning 15 years and presents a radical blueprint for the future control of asthma in children.

Professor Holt and his collaborators (which include multi-disciplinary teams of researchers in several Australian and overseas centres) are at the forefront of an international effort to identify the first triggers responsible for the onset of asthma.

Their studies have shown that while most children develop tolerance to dust mites and pollens during preschool years, others fail to do so and this subgroup is at increased risk for asthma development. However, the highest risk of all is associated with the combination of respiratory allergies and recurring viral infections, which interact in children to create a particularly potent form of airway inflammation.

Professor Holt says these studies collectively have provided a new set of rationales for the prevention of the initial onset of asthma in children.

"New anti-inflammatory therapeutics are being developed all the time but virtually exclusively for established asthma and allergies in adults, but we believe many of these may be effective as preventive agents," he explains.

"We now know enough about how asthma starts and progresses during childhood to identify subgroups of young subjects who are most likely to benefit from early treatment. "We also know that a substantial proportion of severe asthma in the adult population is a direct result of the persistence of the milder childhood form into adulthood, and so halting progression early has the potential to markedly reduce the subsequent burden of chronic adult disease.

"Trials we have designed to test examples of these new approaches are already in progress in Australia and in the US, and others are in the pipeline.

"We are starting to see growing interest from the international pharmaceutical industry in this preventive approach, despite the fact that is completely alien to their traditional thinking which until now has been focussed exclusively on developing drugs to treat established asthma.

"There is also encouraging support from influential organisations such as the National Institutes of Health in the US that set much of the international agenda related to development of new types of medical treatments - so there are exciting times ahead for this important area of research".

More than two million Australians have asthma. Health researchers know that the narrowing and blocking of airways has been on the increase since the 1970s and that asthma can be linked to genetics, environment, pollution and diet.

Professor Holt says that unravelling the complexities of diseases such as asthma has been significantly advanced by using information from the UWA-supported Raine Study which offers local and international researchers more than 21 years of health data.

The study began with a cohort of 2,900 pregnant mothers and focused initially on birth weight. For more than two decades, the mothers and children involved have provided uniquely detailed information on how general health patterns change over time in relation to development, genetics and environmental exposures. The 23-year follow-up of Raine participants funded by NHMRC began in January.

Published in Uniview Vol. 31 No. 2 Winter 2012