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Lung gas holds clue for future tuberculosis treatment

Posted June 6, 2013

Australian researchers have uncovered a link between low levels of the gas nitric oxide in the lungs of tuberculosis patients and the body’s ability to fight the deadly disease, opening the door to potential new treatments.

Nitric oxide, a gas that causes the blood vessels to relax, plays an important role in immune responses as the first line of defence against certain infectious agents, such as tuberculosis.

Senior Clinical Research Fellow with Menzies’ Global and Tropical Health division Dr Anna Ralph said tuberculosis patients had significantly lower levels of nitric oxide in the lung than the average healthy human.

Tuberculosis (TB) affects more than eight million people worldwide annually. It can cause life-long lung damage and death. The research, conducted by the Menzies school of health research, is published in the Journal of Infectious Diseases.

The research suggests a TB patient could recover faster than usual if normal antibiotic treatment is combined with a technique where nitric oxide levels are amplified using substances such as arginine, a protein found in peanuts.

“What our research has shown is that people who have TB don’t make enough of the nitric oxide when they really need it to be fighting off the TB, and that the people that have TB who do well are the ones who can get the biggest rise in their nitric oxide over time,” she said.

However, Dr Ralph said the answer was not as simple as increasing a patient’s arginine intake, since this can be chewed up by the wrong enzymes in people with advanced TB.

“We are looking at this question now, as well as exploring new ways of delivering arginine or other nitric oxide sources,” she said. “This is one part of the whole jigsaw puzzle in terms of looking at how to best control TB.”

The new findings could go a long way in in developing better treatment for those infected with the disease, she said, but the best strategy to beat TB is by preventing it through early detection and treatment of patients and their contacts.

Associate Professor in Paediatrics and Child Health at University of Sydney Ben Marais welcomed the new findings but said further research was needed.

“This is an exciting and novel finding, supporting previous studies that pointed in the same direction, but what needs to be done now is to gain a better mechanistic understanding of how TB influences the exhaled nitrogen oxide levels,” Dr Marais said.

Dr Marais, who also serves on the Centre for Research Excellence in Tuberculosis, said low levels of nitric oxide in TB patients could also be linked to previous medical conditions caused by excessive smoking or malnourishment, both common conditions in developing nations where TB is rampant.

“There are multiple variables that can influence nitric oxide levels in an ill, malnourished, TB patient compared to healthy controls,” he said.

“It definitely adds another layer of evidence to suggest that nitric oxide is clearly influenced by TB disease and might play a roll in susceptibility. It’s just a very complicated area in which to make simple deductions.”

The Menzies School of Health are now continuing their research in Malaysian Borneo.

Source: The Conversation, story by Emma Bourke

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