Researchers at HMRI may have solved why obese people can suffer more severe asthma which is resistant to normal treatments; to potentially develop new symptom reducing treatments.
The team has discovered that obese asthmatics have increased levels of two different types of immune proteins that work together to cause severe disease. Cytokines and inflammasomes pass signals between cells and trigger inflammation in the airways.
Chief Investigator and Associate Professor in Immunology and Microbiology at The University of Newcastle, Jay Horvat, said obesity is a risk factor for asthma and obese asthmatics are more likely to have severe, steroid-insensitive disease. But he said how obesity affects the pathogenesis and severity of asthma is poorly understood.
“We have identified that two types of immune proteins play interacting roles in obesity-associated severe disease. Our findings may mean that new treatments targeting these proteins could reduce symptoms in people with severe asthma,” A/Prof Horvat said.
“Using clinical and experimental studies, we have highlighted a novel link between increased type-2 and NLRP3 inflammasome responses in the airways in obesity-associated severe asthma and the therapeutic potential of targeting type-2 cytokine and/or NLRP3 inflammasome responses,” he said.
HMRI researchers collaborated with Australian and international researchers at University of Technology Sydney, Centre for inflammation Centenary Institute, Imperial College London, Trinity College Dublin and the University of Queensland.
Their research was published in the Journal of Allergy and Clinical Immunology in October 2021. The authors assessed associations between body mass index (BMI) and inflammasome and type-2 immune responses in airways samples of people with asthma. Functional roles for NLRP3 inflammasome and type-2 cytokine responses in driving key features of disease were demonstrated in experimental high fat diet-induced obesity-associated asthma.
“This research is important for our community because Australia’s rates of asthma is among the highest in the world and around one third of the population is classified obese.”
“Asthma and obesity are a significant health and economic burden.”
According to the ABS, around 2.7 million Australians (one in nine or 11.2%) had asthma in 2017-18. People living in inner regional (12.9%) or outer regional and remote Australia (12.7%) are more likely to have asthma than those living in major cities (10.6%). According to the Australian Institute of Health and Welfare, 31% of Australian adults were obese in 2017-18. People living in regional and remote areas are more likely to be obese than those living in major cities.
HMRI researchers are working to unravel how asthma develops to help develop more targeted treatment options. Asthma is often linked to the immune system and inflammation because the immune system is thought to be a regulator of asthma and airways inflammation by producing too many immune factors in response to a stimuli that should not cause such a reaction. Although half of asthmatics can gain some relief from the use of inhaled corticosteroids for the treatment of their asthma, another 50% do not see any therapeutic benefit of this treatment.
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The research team
James W. Pinkerton, PhD
Richard Y. Kim, PhD
Alexandra C. Brown, PhD
Brittany E. Rae, MPH
Chantal Donovan, PhD
Jemma R. Mayall, PhD
Olivia R. Carroll, B. BiomedSci Hon
Md. Khadem Ali, PhD
Hayley A. Scott, PhD
Bronwyn S. Berthon, PhD
Katherine J. Baines, PhD
Malcolm R. Starkey, PhD
Nazanin Z. Kermani, PhD
Yi-Ke Guo, PhD
Avril A.B. Robertson, PhD
Luke A.J. O’Neill, PhD
Ian M. Adcock, PhD
Matthew A. Cooper, PhD