Helping pre-term babies avoid bronchopulmonary dysplasia by controlling inflammatory response

Medical researchers are a big step closer to understanding and controlling the inflammatory responses in pre-terms that can cause devastating heart and lung conditions including bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH).

Professor Claudia Nold and Professor Marcel Nold from The Ritchie Centre at Hudson Institute of Medical Research helping pre-term babies avoid bronchopulmonary dysplasia.
L-R: Professor Claudia Nold, Professor Marcel Nold

It is the immune system’s job to defend the body from potentially harmful invaders. Because there is a myriad of such pathogens, stunningly versatile defence strategies have evolved, including one called type-2-polarised inflammation. 

Type-2-polarised inflammation’s regular job is to fight off parasites and to counterbalance type-1 and -3 responses. However, in pre-term babies with under-developed lungs, this inflammatory response is out of place and out of control, and can cause permanent damage to lung tissue, its supplying blood vessels and the heart.

Controlling inflammatory response

Now a team including Melbourne’s Hudson Institute, Monash University and Monash Children’s Hospital has identified the specific inflammatory responses in pre-terms that drive this process, and identified several risk factors that clinicians treating the mothers before birth and the babies thereafter – that is, obstetricians and neonatal paediatricians – can aim to avoid.

Professor Marcel Nold says the research, published this week in the highly influential journal Science Translational Medicine, is significant in various ways: “The discovery that type-2-polarised inflammation drives cardiopulmonary disease in these babies allows us to now work on ways to control pre-term inflammation and avoid the damage it wreaks.”

“We have also managed to identify that administering the hepatitis B vaccine shortly after birth – as is done in a number of neonatal intensive care units – can augment type-2-driven inflammation, but delaying this vaccine can avoid that problem,” Prof Nold said.

“There is nothing wrong with the hepatitis B vaccine itself,” he said. “But this is a good example of how better understanding of disease mechanisms, in this case regulation of the immune system early in the life of preterm babies, can improve the care we provide to our patients. Simply giving the vaccine later will likely do the trick for most babies.”

Fellow researcher, Professor Claudia Nold, says this research has also provided insight into how some existing treatments work: “We have known that administration of magnesium sulphate and glucocorticoids to the mother before birth have protective properties in preterm infants, and our research now identifies a mechanism by which this protection works.”

“Early life disease often leads to lifelong health problems. Our ultimate goal is to prevent preterm babies developing ongoing conditions, so understanding and controlling how pre-term inflammatory damage occurs is a huge step toward that goal,” she said.

New pre-term treatments – targeting inflammation

The team also believes there could be new treatment strategies to tackle early life cardiopulmonary disease. It has been known for some time that type-2-polarised inflammation also plays a critical role in diseases affecting older children and adults, for example in asthma and allergies, from which at least 2.7 million Australians suffer.

Medications targeting type-2 inflammation have been developed for these patients, and these treatments can now be considered as a means of controlling the type-2-polarised inflammation driving early life cardiopulmonary disease.

In fact, the team recently commenced a clinical trial in which they specifically target the inflammatory mechanisms they have identified as culprits causing illness in preterm babies, to prevent damage to their lung and heart as well as their gut and brain, aiming to offer them and their families a brighter outlook on life.

With Australia’s biggest team of inflammation researchers, Hudson Institute is a leader in the field, and is proud to have led this highly productive collaboration with clinicians and scientists at Monash University and Monash Children’s Hospital as well as the Mercy and Royal Women’s Hospitals and CSL Ltd, along with local, interstate and international partners. Hudson Institute, Monash University and Monash Health are particularly pleased that both lead authors, who are former PhD students of the Professors Nold, namely Dr Bui with a background in science and Dr Lao in medicine, have brought their degrees to a conclusion with a highlight publication that can truly make a difference to young patients and their families.

Collaborators | Monash University, Melbourne, Victoria, Australia; Hokkaido University, Sapporo, Japan; Monash Children’s Hospital, Melbourne, Victoria, Australia; National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan; Australian Synchrotron, Clayton, Victoria, Australia; Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia; Centenary Institute, Sydney, New South Wales, Australia; 13University of Technology Sydney, Ultimo, New South Wales, Australia; Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia; Mercy Hospital for Women, Melbourne, Victoria, Australia; Royal Women’s Hospital, Melbourne, Victoria, Australia; University of Melbourne, Melbourne, Victoria, Australia; Murdoch Children’s Research Institute, Melbourne, Victoria, Australia; Medicum Wesemlin, Lucerne, Switzerland; St. Vincenz Hospital, Limburg, Germany  

Funders | NHMRC, National Heart Foundation, CSL Ltd, Australian Synchrotron, Jack Brockhoff Foundation, Rebecca L Cooper Foundation

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