Radical 'remodelling' theory points to possible asthma cause

PERMANENT changes to a person's airways traced back to early childhood or even the womb may be responsible for soaring asthma rates, it was claimed yesterday.

A combination of genetic and environmental factors is thought to "remodel" the lungs and make them susceptible to asthma attacks, according to a new theory.

The idea is radically different from the traditional view which sees changes to the airways as the result of asthma, not the underlying cause.

Leading asthma expert Professor Stephen Holgate, from the University of Southampton, said: "Our thinking is being turned around. If you begin to uncouple from the traditional thinking, and start to explore why we have failed to overcome the disease, you can open up a whole new range of therapeutic possibilities."

Asthma is becoming increasingly common in Western countries about one in eight British children is now asthmatic but no-one knows why.

An attack happens when a trigger, such as animal fur, pollen, cigarette smoke or dust mites, cause the airways to become inflamed.

Mucus production increases and the muscles surrounding the airways contract, narrowing the space through which air can flow.

It used to be thought that between attacks the airways returned to normal. However, in the 1990s French scientists showed that, in some asthmatic adults, the airway walls are permanently narrowed and thickened.

The smooth muscle surrounding the tubes was three to four times thicker than in non-asthmatics, and much "twitchier" contracting readily in response to even slight stimuli.

Suspicions were aroused that this "remodelling" might be fundamental to the disease.

The idea has now found direct support from studies of tissue samples taken from the lungs of children, New Scientist reported today.

Last year researchers at the Royal Brompton Hospital in London looked at biopsy samples from 19 children with severe asthma. All had airways that were significantly thickened, which is believed to be a key indicator of "remodelling".

The extent of thickening did not correlate with the amount of inflammation, suggesting a pre-existing condition.

Preliminary research on monkeys has since indicated that exposure to common asthma triggers at an early age can cause dramatic changes to the airways.

American scientists found that infant macaques exposed both to dust mite allergen and ozone pollution developed hyper-responsive airways thickened with muscle and collagen.

Further clues have emerged from the discovery of genes linked to asthma.

Professor Holgate has been investigating whether this gene, called Adam33, might be affected by environmental factors.

Laboratory experiments with mouse embryos have shown cigarette smoke do alter the gene's functioning.

Smoke, allergens or items in a mother's diet could cross the placenta and have an impact on Adam33, Professor Holgate speculates.

"Maybe asthma is a developmental problem in the way that the airways form.

"Maybe it gives the child a susceptible set of tubes that have been pre-programmed by interactions between genes and the environment. You could call it 'pre-modelling'."

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