Respiratory
Improve the respiratory health and well-being of all children and young people.
Our group focuses on the lung conditions that cause children to need hospital care.
Our clinicians and scientists aim to use translational experiments and study designs, observation and clinical trials to be at the forefront of setting the global clinical management agenda for children and adolescents with conditions such as
- Cystic fibrosis
- Bronchiectasis
- Sleep-disordered breathing
- Wheezing disorders, asthma and other complex conditions.
More information
Group Leaders
Group Members
Our projects
Next-GEN Cystic Fibrosis (CF) study
We are exploring the mental health of teenagers with cystic fibrosis to establish a more targeted treatment approach to this crisis.
Read more...Inflammation in paediatric pulmonary diseases
This project, funded by the Chan Zuckerberg Initiative, will apply state-of-the-art technologies to characterise pulmonary inflammation in children diagnosed with conditions including wheeze, asthma, cystic fibrosis, idiopathic bronchiectasis, and acute lower respiratory tract infections. Our goal is to identify biomarkers of disease severity for the development of effective treatment strategies.
Developing an immune cell atlas of the healthy paediatric airway
To better diagnose and treat immune-mediated childhood respiratory diseases, we need to understand how the immune environment in disease differs from that of a healthy respiratory system. In this project, funded by the Paediatric Networks for the Human Cell Atlas, we will provide an immune and epithelial cell atlas of the healthy paediatric airway as a reference for understanding globally important childhood lung diseases.
Mononuclear phagocytes as a therapeutic target in cystic fibrosis lung disease
To identify a target for novel anti-inflammatory therapy in children with cystic fibrosis, we need to first develop a greater understanding of the inflammatory pathways in lungs affected by cystic fibrosis. This project, funded by a Vertex Research Innovation Award, will use novel laboratory techniques focusing particularly on mononuclear phagocytes (which are the most common immune cells in the lung) to identify immune cells that cause damaging inflammation. The project will then study these cells in the laboratory to see how they respond to viral and bacterial infection to identify targets for therapeutic intervention.
Synergy CF
We are a key hub of the Synergy CF team, which is a program of work funded by an NHMRC Synergy Grant. In this work, we collaborate with researchers at Telethon Kid’s Institute (Perth, Australia), Emory University (Atlanta, USA), and the University of North Carolina (Chapel Hill, USA) to study early-life lung disease in cystic fibrosis. This project involves an assessment of the role of the microbiome, inflammation, and airway mucous composition in lung disease.
Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF)
AREST-CF is a longstanding collaboration between MCRI and the Telethon Kid’s Institute (Perth, Australia). It is a research program that monitors the health of children with cystic fibrosis from diagnosis at birth across their early life. The program has transformed the understanding of early life CF lung disease and now is expanding to include assessment of adolescent participants. AREST-CF forms the foundation on which many of our other cystic fibrosis-related studies are based.
Optimising Monitoring of Intravenous Aminoglycosides in Children with Cystic Fibrosis
Intravenous antibiotics are a cornerstone of cystic fibrosis care, however, relatively little investigation of the optimum dosing of antibiotics has occurred. This is even though children with cystic fibrosis metabolise medications differently, and optimising dosing increases the chance of therapeutic benefit while reducing the risk of side effects. This project is a collaboration with A. Prof Amanda Gwee (Infectious Diseases group) seeks to define optimal dosing of tobramycin, an intravenous antibiotic commonly used in children with cystic fibrosis.
Digital Health-Based Models of Care for Children with Cystic Fibrosis
Description: (100 words maximum): Digital health tools offer the opportunity to transform the care of those with chronic diseases. Currently, the burden of monitoring for exacerbations of disease falls on children and their families. Digital health tools such as mobile phone applications to collect patient-reported outcomes and wearable devices, offer the opportunity to shift the burden of monitoring off patients and families and to pick up exacerbations at the earliest stage. In this project, we are seeking to utilise these tools to improve the care of children with cystic fibrosis.
Molecular Assessment of Thoracic Empyema
Thoracic Empyema is a complication of bacterial pneumonia. Treatment always involves prolonged antibiotics, and knowledge of exactly which bacteria is causing the infection allows targeted antibiotic therapy. When the infectious agent is unknown, broad-spectrum antibiotics are given which increases the risk of side effects and antibiotic resistance. In this project, which is a collaboration with A. Prof Catherine Satzke (Translational Microbiology group) seeks to improve our ability to detect which bacteria is causing empyema through the use of a multiplex polymerase chain reaction test which can identify the common causes of paediatric empyema.
Bayesian Evidence Adaptive Treatment of Cystic Fibrosis (BEAT CF)
BEAT CF is a clinical registry and adaptive platform trial of children and adults with a diagnosis of Cystic Fibrosis. Those enrolled in the BEAT CF Platform will consent to the systematic collection of their demographic, treatment, outcome (including safety), and other relevant clinical data to better inform the future management of CF exacerbations and inform the BEAT CF Clinical Trial. Participating families are required to answer 2 types of online surveys about how their child is feeling every 3 months when they are well and about their symptoms weekly during an exacerbation.
CLINICAL AND MOLECULAR EPIDEMIOLOGY and IMMUNE CHARACTERISTICS Of RESPIRATORY SYNCYTIAL VIRUS infections IN CHILDREN < 2 years of age (CAMEO study)
CAMEO is a hospital-based observational study of children <2 years of age hospitalised with respiratory syncytial virus (RSV) infection co-led by Drs Anna Do, Paul Licciardi, Prof Kim Mulholland (New vaccines group) and A/Prof Nigel Crawford (SAEFVIC). It includes clinical, virological, immune and laboratory arms. Real-time surveillance of RSV positive cases and g-gene and whole-genome sequencing of viral samples is undertaken to evaluate the clinical and molecular epidemiology of severe RSV infections at The Royal Children’s Hospital. A subset of children undergo comprehensive immunological profiling to identify biomarkers of severe disease.
COVID-ALI – Air-Liquid interface: using a human airway epithelium model in COVID-19
This study uses an established epithelial cell culture (“air-liquid interface”) technique to create an in vitro ‘living’ model of the human respiratory epithelium. In collaboration with A. Prof Catherine Satzke (Translational Microbiology group) and Prof Kanta Subbarao (Peter Doherty Research Institute), are exploring infection and transmission of viruses such as SARS-CoV-2, RSV and influenza and viral-bacterial co-infection, to help understand disease pathogenesis and to explain potential therapeutic targets.
REPEAT trial – Reducing exacerbations in people with PCD using Erdosteine and Azithromycin Therapy
Primary ciliary dyskinesia (PCD) is a rare, incurable disease that causes chronic respiratory infections and bronchiectasis. The European Respiratory Society has identified bronchiectasis as one of the most neglected lung diseases in current clinical practice. This NHMRC-funded randomised controlled trial (led by Queensland Children’s Hospital) evaluates a currently prescribed antibiotic (but not licensed for long-term use in PCD) azithromycin and a novel mucolytic (erdosteine) in reducing exacerbations of bronchiectasis in children and adults with PCD.
Australian National Non-Cystic Fibrosis Bronchiectasis Registry (Lung Foundation Australia)
National Clinical Registry of adults and children with bronchiectasis. Longitudinal data collection from enrolled patients recruited via the Royal Children’s Hospital multi-disciplinary bronchiectasis clinic, led by Children’s Hospital Queensland and Lung Foundation, Australia.
Oral bacterial lysate to prevent persistent wheeze in infants after severe bronchiolitis; a randomised placebo-controlled trial (BLIPA)
MRFF-funded parallel, multicentre, double-blinded, superiority randomised controlled trial in 5 Australian sites to complement the United Kingdom (UK) National Institute of Health Research (NIHR) funded study, led by Prof Jonathan Grigg. Our primary hypothesis is that treatment with oral bacterial lysate reduces the incidence of doctor-diagnosed wheeze 19-24 months post-hospitalisation for bronchiolitis.
Evaluation of multiple breath washout as a screening test for bronchiolitis obliterans syndrome in paediatric haemopoietic stem cell transplant patients
Children who receive a haemopoietic stem cell transplant are at risk of developing bronchiolitis obliterans syndrome (BOS). Multiple breath washout (MBW) is a non-invasive test that has been more sensitive than traditional measures of lung function, such as spirometry. This 24-month longitudinal study aims to determine if MBW can detect the onset of BOS sooner than spirometry and allow for earlier intervention.
Gut Lung Axis in Early Cystic Fibrosis
Increasing evidence suggests a relationship between bacterial communities in the gut and the lung, likely influenced by the immune system. This study explores this relationship in cystic fibrosis through the molecular analysis of serial stool, oral, nasal, lung washing and blood samples collected from infants aged 0-2 years. Associations between the gut-lung axis and clinical outcomes such as growth, and lung disease severity, will be assessed to develop therapeutic targets.
Funding
- Chan Zuckerberg Initiative Inflammation Network
- Paediatric Networks for the Human Cell Atlas
- Vertex Research Innovation Award
- The University of Sydney NSW 2006. Australia
- National Health and Medical Research Council (NHMRC)
Collaborations
- Wal-yan Respiratory Research Centre, Telethon Kid’s Institute (Perth, Australia)
- Bioinformatics and Computational Biology, Peter MacCallum Cancer Centre (Melbourne, Australia)
- Marsico Lung Institute, University of North Carolina (Chapel Hill, USA)
- Tirouvanziam Laboratory, Emory University (Atlanta, USA)
- Sanders DB, Indianapolis, Indiana (USA)
- Bush AB, Imperial College, London (UK)
- Varki, S, Christian Medical College, Vellore (India)
- Davis, S, University of North Carolina (Chapel Hill, USA)
- King, P, Monash University.
- Ooi, K, Sydney Children’s Network, NSW.
- Snelling, T, University of Sydney, NSW
- Cheong, J. Women and Children’s Hospital, Melbourne.
- An, P, University of Medicine and Pharmacy, Ho Chi Minh City
- WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Murdoch Children's Research Institute
- Queensland Children’s Hospital, Brisbane, QLD
- Menzies School of Health Research, Darwin, NT
- Translational Microbiology, Murdoch Children's Research Institute
- Infectious Diseases, Murdoch Children's Research Institute
- New vaccines, Murdoch Children's Research Institute
- SAEFVIC, Murdoch Children's Research Institute
- Marsland Laboratory, Department of Immunology and Pathology, Monash University (Melbourne, Australia)
Featured publications
Single cell flow cytometry profiling of bronchoalveolar lavage in children. American Journal of Respiratory Cell and Molecular Biology 2020; 63(2) 152-159. S. Shanthikumar, M Burton, R Saffery, S Ranganathan, MR Neeland.
The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis. Thorax 2017; 72:1104-1112 Frayman KB*, Armstrong DS, Carzino R, Ferkol TW, Grimwood K, Storch GA, Teo SM, Wylie KM, Ranganathan SC.
Maternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring. Nat Commun. 2020 Mar 24;11(1):1452. Vuillermin PJ, O'Hely M, Collier F, Allen KJ, Tang MLK, Harrison LC, Carlin, JB, Saffery R, Ranganathan S, Sly PD, Gray L, Molloy J, Pezic A, Conlon M, Topping D, Nelson K, Mackay CR, Macia L, Koplin J, Dawson SL, Moreno-Betancur M, Ponsonby AL; J. Craig Venter Institute; BIS Investigator Group.
Worsening respiratory function to 8 years in infants born extremely preterm. N Eng J Med 2017;377(4):329-337. Doyle LW, Carse E, Adams AM, Ranganathan S, Opie G and Cheong JLY for the Victorian infant Collaborative Study Group.
Early Lung Disease in Infants and Preschool Children with Cystic Fibrosis: What Have We Learnt and What Should We Do About It? Am J Respir Crit Care Med. 2017;195(12):1567-75. Ranganathan SC, Hall GL, Sly PD, Stick SM, Douglas TA; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF).