Taking the pressure off little lungs and hearts

New research into an anti-inflammatory drug for treating lung disease in pre-term babies has shown it also has the potential to prevent the disease’s subsequent complication, pulmonary hypertension (PH), a vascular condition that leads to heart failure and death in 50 per cent of cases.

Associate Professor Claudia Nold
Associate Professor Claudia Nold

Research conducted in 2017 by Hudson Institute found that the anti-inflammatory drug, interleukin 1 receptor antagonist (IL-1Ra), could save preterm babies from the severe lifelong effects of the lung disease bronchopulmonary dysplasia (BPD) if given within hours of delivery.

In an extension of earlier pre-clinical research, Associate Professor Claudia Nold, Professor Marcel Nold and PhD student Christine Bui have now shown the drug has a two-fold protective benefit for new born babies. In the study, published in Frontiers in Immunology, the researchers found that the drug is effective in not only averting BPD but also in preventing PH, which is the most serious complication associated with BPD.

Pulmonary hypertension

PH, which occurs in 15-30 per cent of BPD patients, is a condition that arises from the damage BPD causes to blood vessels and tissue in the lung.

In a healthy lung, the right chamber of the heart pumps blood through the pulmonary artery and into the lung to oxygenate the blood. The blood is then pumped into the left chamber of the heart and into the circulation system, where it supplies oxygen to the tissues of the body.

In babies with BPD, the right chamber of the heart pumps blood through a lung with fewer blood vessels for the blood to flow into, causing pressure in the pulmonary artery to rise.

This increase in pressure over-taxes the heart muscle causing right heart failure, which eventually reduces blood flow to the tissues to a critical level that is unable to support life.

 BPD onset

Premature newborn babies’ immature lungs are often unable to cope with the essential and life-saving respiratory support they are exposed to in hospital.

Lead researcher, A/Prof C Nold said, “Up to 60 per cent of preterm babies within the lowest birth weight group develop BPD, an inflammatory lung disease that disrupts normal development of the lungs by inhibiting alveolar (air sac) and blood vessel growth.

“BPD also causes tissue damage, further reducing the volume of lung tissue, blood vessels and alveoli. The more premature a baby at birth, the higher the risk of BPD,” she said.

Delivering IL-1Ra

Monash Children’s Hospital Professor for Paediatric Immunology and Consultant Neonatal Paediatrician, Prof M Nold said, “In this pre-clinical study, we found that by blocking early onset inflammation with IL-1Ra, we could prevent alveolar damage and limit blood vessel loss in the lung.

“We could both improve the development of the lungs, as well as rescue blood vessel development. This meant there was less pressure on the pulmonary circulation artery, thereby preventing BDP-PH.

“These preclinical findings may prove highly useful for pre-term infants going forward, as we currently have no safe and effective treatment for BPD and BPD-PH.”

How does IL-1Ra work?

IL-1Ra is a natural protein and is the inhibitor of IL-1, one of the most potent inflammatory mediators. The body uses IL-1Ra to curb excessive inflammation. In some diseases that involve chronic inflammation such as rheumatoid arthritis, the patient often does not produce enough IL-1Ra, and in these cases the IL-1Ra can be used to supplement the body’s natural stores and act as an anti-inflammatory drug.

BPD-PH facts

  • Almost 1 in 10 babies in Australia are born premature
  • Up to 60 per cent of preterm babies will develop BPD
  • 15-30 per cent of BPD patients will develop PH
  • PH leads to death in 50 per cent of cases
  • The anti-inflammatory drug IL-1Ra has been used safely by more than 150 000 patients since its introduction to clinical medicine in 1993.

Collaborators | Australian Synchrotron; Monash Children’s Hospital; Monash University; University of Rzeszow, Rzeszow, Poland; University of Otago, Dunedin, New Zealand; National Cerebral and Cardiovascular Center Research Institute, Suita, Japan; Department of Pharmacy, Amsterdam UMC, Amsterdam, Netherlands

 Funders | Future Leader Fellowship – The National Heart Foundation of Australia, Larkins Fellowship, Victorian Government’s Operational Infrastructure Support Program, Rebecca Cooper Foundation, IMBL at the Australian Synchrotron

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Research Group leading this work