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Bronchiolitis: developing ways to prevent or treat serious lung infections

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What did the project achieve?

Bronchiolitis is a distressing, potentially life-threatening lung condition, commonly caused by infection with the respiratory syncytial virus (RSV). Sadly, over 100,000 children under five years old will lose their lives to RSV each year worldwide.1 There is an urgent need to understand why some children are more susceptible to severe RSV infectionsand to find ways to prevent and treat life-threatening infections.

“The outcomes of this research have the potential to be used in predicting risk of RSV infection and/or severe illness, to enable the targeting of protective interventions, and may lead to new approaches to prevent and treat RSV infection in the future,” says Professor Donald J. Davidson of the University of Edinburgh.

This research focused on cathelicidin, a naturally-produced substance made by the body that is thought to act as a ‘shield’ in the nose, blocking the entry point for RSV. The team studied nose fluid samples from premature and full-term babies and young children in the UK and Europe. They wanted to find out when cathelicidin is first made, track its levels over time and understand how its levels influence the risk of severe RSV infection.

“This has enabled us to establish the normal levels of cathelicidin in the nose – and how these levels change over time after birth,” says Professor Davidson. “We’ve also discovered how its levels can vary depending on the baby’s season of birth and with the development of healthy populations of bacteria in the airways.”

In laboratory-based studies, the researchers have also made new discoveries toward understanding the potential of using compounds that can boost cathelicidin in the cells lining the airways to help protect against RSV infection and the spread of the virus.

“Receiving Action funding was a fantastic boost for our research, enabling us to collect and analyse clinical samples from infants and study potential new anti-viral treatments in the laboratory,” says Professor Davidson. “We hope that our findings will ultimately help inform new approaches to prevent and treat babies and young children with RSV infections, for which no effective treatment currently exists.”

This research was completed on

Bronchiolitis is a distressing, potentially life-threatening lung infection that affects over 33 million babies and infants worldwide every year.1 It is very often caused by the respiratory syncytial virus (RSV), but little is known about why some children develop potentially lethal infections while others have mild symptoms. Professor Donald J. Davidson at the University of Edinburgh is investigating the protective effects of cathelicidin, a naturally-occurring anti-viral compound. He is aiming to develop ways to boost the body’s cathelicidin production to help prevent or treat RSV infections, saving babies lives and reducing the heartache of life-threatening infections.

This grant is also supported by The Chief Scientist Office (CSO) Scotland.

How are children’s lives affected now?

Bronchiolitis is typically caused by viral infection leading to blockages in the tiny airways of the lungs, making breathing difficult. It is more common in children who are born prematurely, have congenital heart disease, a weakened immune system or are under six months old.

Around one in three children in the UK will develop bronchiolitis before their first birthday, with around 45,000 admitted to hospital each year for monitoring or treatment.2 Infection with the respiratory syncytial virus (RSV) is the most common cause.  

“In older children and adults this common and highly contagious virus may cause mild, cold-like symptoms – but it can be much more serious for young infants,” says Professor Davidson. “Unfortunately, there is currently no vaccine available to protect against RSV – and there are no effective treatments.”

Sadly, over 100,000 children under five years old will lose their lives to RSV each year worldwide.1

“Understanding why some children are more susceptible to severe RSV infections could lead to new ways to protect babies from serious illness,” says Professor Davidson.

How could this research help?

“Our aim is to find ways to prevent or treat potentially life-threatening lung infections caused by RSV in young children,” says Professor Davidson.

The team are building on from their previous discovery about a naturally-produced substance in the body called cathelicidin.

“We believe that infants, particularly those born too soon, initially have very little cathelicidin in their noses,” says Professor Davidson. “The absence of a ‘cathelicidin shield’ at this entry point for RSV, may increase their risk of a serious infection.”

The team are measuring cathelicidin in the noses of babies (born full-term or prematurely) – to find out when they start to make it, track its levels as children grow, and see how levels influence their risk of severe RSV infection.

“We will now be able to extend our studies of naturally-produced cathelicidin with laboratory work to see if cathelicidin-boosting strategies can help protect against RSV,” says Professor Davidson. “If our results are encouraging, our goal is for clinical trials within five to ten years – to test ways to prevent or treat serious RSV infections.”

References

  1. Shi, T. et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. The Lancet 2017; 390(10098): 946-958.
  2. NHS Choices: https://www.nhs.uk/conditions/bronchiolitis/complications/ [website accessed 28 August 2018]

 

 

 

Project Leader Professor Donald J Davidson, MBChB PhD FRSB
Project Team Professor Debby Bogaert, MD PhD Professor Jürgen Schwarze, Dr. med. habil. FRCPCH Dr Catherine M McDougall, MSc MBChB PhD MRCPCH Professor James P Boardman, BSc (Hons) MBBS MSc PhD FRCPCH Professor Steve Cunningham, MBChB PhD FRCP FRCPCH
Project Location University of Edinburgh Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh
Project Location Other MRC Centre for Reproductive Medicine, Queen’s Medical Research Institute, University of Edinburgh
Project duration 2 years
Date awarded 25 July 2018
Project start date 1 February 2019
Project end date 30 September 2022
Grant amount £180,527
Grant code GN2703

 

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