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July 2022 - June 2023

Wal-yan Centre Annual Report

About the Wal-yan Respiratory Research Centre

The English translation of our Noongar name is “Place of Healthy Lungs”. “Wal-yan” means lungs, and “Warlang-up” means healthy place. We would like to acknowledge Walter Jnr McGuire and Elder May McGuire for the Noongar name of place with English translation.

The Wal-yan Respiratory Research Centre - a powerhouse partnership between Telethon Kids Institute, Perth Children’s Hospital Foundation and Perth Children’s Hospital - brings together clinicians, scientists and community members from across the globe with a united goal to prevent childhood respiratory illness and ensure that all children have healthy lungs for life.

Our Vision To ensure that every child has healthy lungs for life.

Our Mission

Acknowledgement We would like to acknowledge and pay our respect to Australia’s Aboriginal and Torres Strait Islander peoples as the traditional custodians of the lands, the waterways, and the skies across Australia. We would like to thank the Aboriginal and Torres Strait Islander people for caring and sharing the land on which we are able to learn and undertake our respiratory research. We would like to acknowledge the Noongar Nations and especially the Noongar Whadjuk People on whose land the Wal-yan Warlang-up Respiratory Research Centre at the Telethon Kids Institute is situated. We would like to acknowledge and thank the traditional custodians of all the lands we have worked in across the Kimberley and Pilbara regions over the past year, including but not limited to Tawuwu, Bardi, Jawi, Karajarri, Juwalinny, Mangala, Nyungamarta, Yulpartja, Jaru, Kukatja and Marapikurrinya people. We pay our respects to elders past and present. We share our friendship and our kindness. We work together to ensure that every child has healthy lungs, for life.

To prevent and cure respiratory illness in children through world-class, multidisciplinary research, that will drive pioneering discoveries out of the labs and into the community, across WA, Australia and beyond. Our work extends across six strategic research areas:

Beating Chronic Lung Disease Early Life Influences Respiratory Infections and Immune Systems Lungs and the Environment Indigenous Health Implementation into Clinics

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Contents Highlights

Community Involvement and Engagement

Global Reach and Impact

Funding and Developing our Researchers

Awards and Positions

Honours and PhD Student Highlights

Published papers

Grant Income

Wal-yan Centre Expenditure

Our supporters

Message from the Director In reflecting on the past year, I am inspired by the remarkable achievements made by our dedicated team and supportive community. In Australia, the alarming reality remains that around one million children are living with serious respiratory diseases, with over 110,000 of these children residing in Western Australia. Over the fourth year of the Wal-yan Centre’s powerhouse partnership between Telethon Kids Institute, Perth Children’s Hospital Foundation and Perth Children’s Hospital, the Centre has continued its unwavering commitment to making a significant impact on the health of these children through groundbreaking research. Our 140-strong team, working tirelessly on over 100 research projects, has been instrumental in driving our mission forward. While it is impossible to mention every achievement in this report, I would like to highlight some notable milestones from the past year. We have accelerated our research efforts in developing an innovative and patented treatment for childhood wheezing and asthma. Our groundbreaking work utilizing a new class of drugs to enhance airway epithelial repair brings hope to millions of children suffering from these respiratory conditions. In a world-first discovery, we have provided evidence that not all biodiesel fuels are equal. Our research has demonstrated that the exhaust from certain biodiesel types,

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particularly those derived from beef tallow, can produce more toxic health effects than others. This vital knowledge will shape environmental practices and promote healthier alternatives for the wellbeing of our children. Other study results have shown the effectiveness of a common asthma drug for very premature babies who go on to suffer from lung complications. By expanding our understanding of treatment options, we can provide better care and outcomes for these vulnerable infants. I am delighted to share that we have reached a significant milestone in our 20-year MAVRIC study by recruiting our 1000th participant. This ongoing study aims to better understand and predict why specific children experience recurrent respiratory exacerbations, while also developing new treatments to reduce the likelihood of asthma development. Our regional wet cough work has also made significant advancements, focusing on the prevalence and management of chronic wet cough in Aboriginal children to improve their long-term lung health. These efforts are a testament to our commitment to addressing health disparities and ensuring equal access to care for all children. In line with our commitment to innovation, we have continued to develop a clinical program for implementing phage therapy. This program specifically targets bacterial infections resistant to antibiotics, including lung infections in

children living with cystic fibrosis. By exploring alternative treatment options, we aim to provide new hope for those affected by these challenging conditions. Furthermore, we are proud to have acquired state-of-the-art lung function testing equipment dedicated to research purposes. This valuable resource will enhance our capabilities and facilitate groundbreaking studies that push the boundaries of respiratory research. Looking towards the future, the Wal-yan Centre is embarking on a new additional research direction—investigating the impact of climate change on children’s respiratory health in Australia. Our team is merging geospatial data on health, climate, and socio-economics to conduct a comprehensive whole-of-continent study that will be crucial for informing policies and interventions nationally. As we progress in our mission, we are cognizant of the challenges faced by the research community. Securing funding and providing viable career pathways for emerging scientists remain critical priorities. Rest assured, we will continue to advocate for the necessary resources to support our research and nurture future leaders in the field. Our achievements would not be possible without the unwavering support of our community. I extend my heartfelt thanks to our study participants, their families, our community reference group members, research buddies, collaborators and partners, and our corporate

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and philanthropic supporters. Your commitment and collaboration have played an instrumental role in improving, extending, and saving the lives of children suffering from various respiratory diseases. I would also like to express my gratitude to each, and every staff member involved in the Wal-yan Centre. Your dedication and tireless efforts have brought us closer to our vision of a healthier future for children battling respiratory illnesses. Together, we will continue to drive innovation, find solutions, and transform lives. Professor Stephen Stick Director, Wal-yan Respiratory Research Centre

Highlights

These researchers at the Walyan Centre have discovered an FDA-approved medication traditionally used to treat pain in children and adults – that enhances repair and reduces inflammation in airway epithelial cells from children with asthma. The research team, including collaborators at Monash University, was granted a patent in 2022 on the ‘Promotion of Epithelial Repair’, paving the way for a potentially new class of drugs which target a previously unknown asthma pathway.

Healing airways so kids with asthma can breathe better An exciting discovery is that the airways of children with asthma do not repair effectively when injured, for example, following virus infections. The group has identified a mechanism to restore healthy repair using a new class of drugs that will protect young sufferers from ongoing lung damage and improve their long-term health outcomes.

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The team, led by Dr Thomas Iosifidis, is now investigating the preclinical safety and effectiveness of these therapeutics, prior to clinical trial assessment. In the near future, this novel treatment solution will help heal the airways of children with asthma, protecting them from ongoing damage, and improving their long-term health outcomes. Read the full story here

Common asthma drug gives hope for better lung health for some preterm babies

Biodiesels not as clean and green as they seem

A new study has found a common asthma drug is effective for some very premature babies who go on to suffer from lung complications.

In a world being urged to embrace renewable options, biodiesel fuels – made from plants and animal by-products – are increasingly touted as a greener, cleaner choice than traditional diesel.

Every year nearly two million babies are born at less than 32 weeks of gestation globally. These babies face a broad range of health challenges, including respiratory problems throughout life. So far, there are no specific treatments to improve the lung health of children surviving preterm birth after discharge from the neonatal intensive care unit. A clinical trial led by Associate Professor Shannon Simpson aimed to determine the effectiveness of a common asthma medication, ‘Flixotide’, for treating ongoing breathing problems in preterm born children aged six to 12 years old, who were born at less than 32 weeks gestation.

Flixotide experienced modest improvements in lung function, compared to children in the control group, but nearly one quarter (23 per cent) of children experienced a significant improvement in their lung function. In addition, the study identified a group of children who benefited the most from corticosteroids, based on two markers of health measured at the start of the study. This finding may one day help clinicians identify which children will benefit the most from corticosteroid treatment. The findings of this study may change the way some preterm babies are treated, leading to improved respiratory health in this population.

The five-year Preterm paediatric Inhaled CorticoSteroid Intervention (PICSI) study found that children who received

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Read the full story here

But world-first evidence being produced by Dr Katherine Landwehr has raised questions about the health impacts of these seemingly friendly products. Dr Landwehr’s work has, for the first time, proved not all biodiesel fuels are equal, with the exhaust from some – especially biodiesel made from beef tallow – producing more toxic health effects than others. The findings have revealed that even short exposures to diesel and biodiesel exhaust can have toxic effects. Read the full story here

Community bands together to improve lung health of Aboriginal children in East Kimberley

20-year MAVRIC study celebrated recruitment of its 1000th participant

The study was the first to discover that a newly recognised species of rhinovirus (the common ‘cold’ virus) is the most common cause of children presenting to hospital with acute wheezing and asthma. Present research is aimed at uncovering why this new virus is such a serious worldwide problem in young children.

A co-designed and culturally secure intervention to improve medical follow-up for Aboriginal children hospitalised with acute chest infections resulted in higher follow-up rates and improved longerterm lung health outcomes for children.

A three-month intensive health promotion campaign in the East Kimberley region aimed to raise awareness of the dangers of a chronic wet cough in Aboriginal children.

The MAVRIC (Mechanisms of Acute Viral Respiratory Infection in Children) study celebrated the recruitment of the 1000th participant to the study, eight-year-old Sullivan Strahan. The 20-year study, being led by Professor Peter Le Souef and Associate Professor Ingrid Laing, is designed to discover why some children are more susceptible to getting severe respiratory illnesses when they have a viral infection.

Study shows lung health of Aboriginal children hospitalised with chest infections improved following co-designed intervention

The ongoing study also continues to try to better understand and predict why particular children keep returning to hospital with respiratory exacerbations, and to develop new treatments which reduce the likelihood of them developing asthma. Read the full story here

Researchers from the Wal-yan Centre, led by Professor André Schultz, and the Kulunga Aboriginal Unit at the Telethon Kids Institute partnered with Kimberley Aboriginal Medical Services, Yura Yungi Aboriginal Medical Services, Aboriginal families, and clinicians in the East Kimberley to improve the lung health of Aboriginal children. They aimed to raise awareness and to develop solutions for timely detection, accurate diagnosis, and optimal management of chronic wet cough in Aboriginal children. A wet cough experienced by a child for more than four weeks can be a sign of underlying infection known as protracted bacterial bronchitis. If left untreated, this can lead to irreversible, life-shortening lung damage known as bronchiectasis. Read the full story here

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New treatment option for West Australians with cystic fibrosis one step closer thanks to generosity of Conquer Cystic Fibrosis Access to phage therapy, a treatment option for antibiotic resistant superbugs, is now one step closer for people with cystic fibrosis (CF) in WA thanks to a $500,000 donation from Conquer Cystic Fibrosis to the Wal-yan Centre. Antimicrobial resistance occurs when bacteria develop ways to resist antimicrobial medicines, such as antibiotics. These resistant bacteria then grow causing very bad and uncontrolled infections.

Individuals living with CF and their families need alternatives to antibiotics to fight against the harmful bacteria that cause these lung infections – a powerful new weapon is phage therapy. The Wal-yan Centre is home to the Phage WA team – a network which aims to make phage therapy a reality to treat a variety of bacteriacaused infections, including lung infections in children living with CF. The team is led by Professor Stephen Stick and Associate Professor Anthony Kicic.

This is a big problem for people living with CF because they usually take high-dose, longcourse antibiotics frequently to fight serious and potentially deadly lung infections.

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Read the full story here

Aboriginal children hospitalised with acute chest infections are at-risk of developing bronchiectasis, which is a chronic, debilitating and life-shortening lung disease. The earliest sign of chronic lung disease after hospitalisation is usually a wet cough for more than four weeks. If the ongoing wet cough is managed early, bronchiectasis can often be prevented. Therefore, effective follow-up after being discharged from hospital is essential. The study, co-led by Dr Pam Laird and Professor André Schultz, demonstrates the urgent need for a national follow-up strategy for Aboriginal children who have been hospitalised for acute chest infections, to prevent more serious lung disease. Read the full story here

Study finds high rates of chronic lung disease in remote-living Aboriginal children A study co-designed and conducted in partnership with Aboriginal communities found that almost one in five children across four remote Kimberley communities has some form of chronic lung disease. New trial aims to nip chronic lung disease in the bud for First Nations kids The team were successful in securing a $1.97 million Medical Research Future Fund grant to develop and trial an effective, culturally secure follow-up strategy, to ensure that Aboriginal children around the nation are receiving effective medical follow-up and treatment. The four-year trial will be led by Dr Pam Laird from Telethon Kids Institute in collaboration with The University of Western Australia and the Menzies School of Health Research, with a team of researchers from Telethon Kids, UWA, the Queensland University of Technology, the University of Queensland, and Curtin University. The group will work with partner organisations from Queensland and from the Kimberley and Pilbara regions in Western Australia, including Aboriginal medical services that support remote-living First Nations communities.

Analysis of worldwide research showed that despite advances in neonatal care, preterm babies have lower lung function throughout their life A review of existing research on lung function in individuals born preterm found that whilst there have been overall improvements in lung function due to advances in neonatal care, individuals born preterm continue to have lower lung function throughout their life compared to babies born fullterm. Furthermore, the research review showed that where a baby is born can have an impact on their lung function outcomes, with preterm born babies in Scandinavian countries having better lung function outcomes than babies born in similarly economic developed countries.

Co-authored by Dr James Gibbons, the research paper was published in JAMA Pediatrics, which is a peerreviewed medical journal published by the American Medical Association. This paper suggests that there is still further work to do in determining what impacts poorer lung function in people born prematurely. Read the full story here

New study to find COVIDfighting properties in existing medications

New study to better understand how bronchiectasis develops during childhood

Nearly 50 existing prescription medications already used by Australians will be tested by new research in the fight against COVID’s mutant variants.

A new research project – the WA Paediatric Bronchiectasis Cohort Study – officially commenced with the aim of looking at children with bronchiectasis in Western Australia, to better understand how this disease develops during childhood.

The new research, led by Associate Professor Anthony Kicic, will investigate the anti-viral properties of 45 medications already approved by the Therapeutic Goods Administration. Associate Professor Kicic said repurposing existing medications may offer a new shield in the battle against the emerging threats of COVID variants that are continuing to prove deadly. This research will provide doctors with an insight into what medications they can prescribe to help someone with COVID. Read the full story here

Bronchiectasis is one of the most underdiagnosed and neglected lung diseases in children and adults across the world. Importantly, early detection and treatment of bronchiectasis in childhood can prevent and slow progression of lung damage. This study, led by Dr Kathryn Ramsey, aims to gain knowledge into the disease mechanisms of childhood bronchiectasis so that targets for treatment can be identified. Read the full story here

The results reveal 17.9 per cent of the children screened had a chronic respiratory disease – either protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD), bronchiectasis, or asthma. PBB and CSLD are conditions which, if not properly treated, can lead to bronchiectasis – a disease that eats away at the lungs, causing progressive, irreversible, and life-shortening damage. The findings of this study – led by Dr Pam Laird - will help to fill a serious information gap about how common and serious chronic lung disease is in Aboriginal children, and how important it is to urgently tackle it in a culturally secure way. Read the full story here

Read the full story here

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A team of clinician-researchers from the Wal-yan Centre worked with the Kimberley Aboriginal Medical Service and 16 Aboriginal community researchers to screen almost 400 children aged 0-18 years living in the four communities.

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Development of new therapies for respiratory viruses supported by State Government grant A project to be undertaken by a team of researchers at the Wal-yan Centre, led by chief investigator Professor Stephen Stick, aims to develop interventions that could provide protection in the event of a new pandemic, and against common viruses already infecting children and adolescents in Western Australia. The two-year project is made possible thanks to nearly $600,000 in funding provided by the State Government’s WA Child Research Fund. The project will identify the factors that determine the outcome of viral exposure and infection. The development of new therapies for respiratory viruses, including new viruses with pandemic potential, is a World Health Organization priority. Read the full story here

New state-of-the-art lung function testing equipment becomes a reality Respiratory function testing is essential for the diagnosis, monitoring, and treatment of a range of conditions, including asthma, cystic fibrosis and the chronic lung disease of prematurity. However, these tests are highly specialised and require adapted equipment to be suitable for testing in children. Thanks to funding support from the Stan Perron Charitable Foundation, the Telethon Kids Institute and the Walyan Centre, the Centre now has a range of new specialist respiratory function testing equipment, dedicated for research use, on hand. In addition, portable equipment is available, to enable bedside and community-led research in rural and remote communities, which is vital for respiratory research. Program Manager of the Children’s Lung Health team, Dr Elizabeth Smith, said the new equipment is invaluable for the research work her team undertakes.

300th participant recruited to crucial respiratory research program Research into innovative treatments for people with asthma and antibiotic resistance supported by Innovation Fellowships Two Wal-yan Centre researchers were awarded a 2022 Innovation Fellowship supported by the WA Government’s Future Health Research and Innovation Fund. Associate Professor Anthony Kicic (pictured below) was awarded $145,036 for enabling the establishment of a phage bioreactor facility for human therapeutic application. Dr Tom Iosifidis (pictured above) was awarded $110,726 to investigate an innovative treatment to enhance airway repair, which is anticipated to reduce asthma exacerbations and hospitalisation. Read the full story here

A research program, which enables over 25 important respiratory research studies to be undertaken, celebrated the recruitment of its 300th participant. The Western Australian Epithelial Research Program (WAERP) is a community cohort biobank that collects and stores respiratory epithelial cells from the upper (nose) and lower (trachea) airways of Western Australian children and adults undergoing non respiratory elective surgery. Airway cells are known to be the first line of defence against respiratory viruses, bacteria, pollutants and allergens.

WAERP Study Recruitment Officer Amy Greenly said that by taking part in the program, the participants are bringing hope for people with respiratory conditions.

The WAERP biobank supports numerous and diverse research studies intended to improve understanding and assessment of treatments for respiratory conditions.

Read the full story here Wal-yan Respiratory Research Centre Annual Report 2023 Page 12

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Read the full story here

Research to help identify which children will develop asthma and to design more specific asthma treatments supported by Federal Government funding Research focussed on identifying which children will develop asthma, and developing more specific asthma treatments, has been supported by the National Health and Medical Research Council’s (NHMRC) Ideas Grants. This study will address the main gaps in asthma research that have delayed progress in preventing and treating asthma over the past 30 years - including a lack of understanding of why only some children develop asthma, and the lack of early susceptibility factors (biomarkers) to detect these children. The project – which will be undertaken by a team of expert children’s respiratory researchers, including Professor Peter Le Souef and Associate Professor Ingrid Laing - will determine if the future development of asthma in a child is influenced by changes to how their genes work as a result of behavioural and environmental factors, known as epigenetic changes. As epigenetic changes are reversible, this project has the potential to open the way for the development of entirely new therapies to counter epigenetic changes and achieve the largescale prevention of the development of asthma. Read the full story here

Patients with antibiotic-resistant lung infections to receive promising phage therapy treatment as part of new trial New study to determine if it’s safe for children born preterm to attend day care A new study to determine if it’s safe for children who were born preterm to attend day care officially commenced. Children born preterm are seven times more likely to be hospitalised within the first year of life with respiratory infections when compared with babies born at term. As day care is associated with increased risks of acquiring these respiratory infections, one of the most frequently asked questions by parents of children born preterm is whether it is safe to attend day care. The aim of the Kids INfections and Day care’s Effects on the lungs in those born Early (KINDEE) study is to improve lung health outcomes in children born preterm by better understanding the impact that respiratory infections and day care attendance have on their lung health during later childhood. The study’s lead investigators are Associate Professor Shannon Simpson and Dr James Gibbons. Read the full story here

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Patients with lung infections that are not responding to antibiotics will be treated with phage therapy as part of a new translational trial program. This will be the first time that a coordinated, standardised approach to assess the effectiveness of phage therapy for treating antibioticresistant pseudomonas lung infections in humans has been undertaken. The three-year program, to be led by Associate Professor Anthony Kicic, has received $1,972,632 funding under the Federal Government’s Medical Research Future Fund. Read the full story here

New risk factor identified to help predict the long-term lung health of young adults born very preterm A study which set out to determine ways to predict the long-term lung health of young adults born very preterm has shown that a childhood history of respiratory hospital admission should be a key consideration in the management of preterm children and adults. In addition, the study found that having a history of asthma in the mother or a personal history of allergies did not have any clear effect. As more and more babies are surviving premature birth due to better neonatal care, it’s important to identify those who are at the highest risk for longterm lung problems. The information gathered in this study, led by Associate Professor Shannon Simpson, can help healthcare providers better manage the long-term lung health of preterm children and adults. Read the full story here

466 babies recruited to AERIAL study The AERIAL study, in partnership with the ORIGINS Project (Joondalup Health Campus), endeavours to understand if exposures during pregnancy and early life can affect the cells lining the airways (epithelial cells) in newborns and whether this is associated with the development of wheeze, allergy and asthma later in childhood. We launched the AERIAL Study in August 2020, and this year saw the recruitment of the final participant, which includes 14 siblings, 2 sets of twins, 310 placenta samples and 462 newborn nasal samples collected – an extraordinary effort. The AERIAL families continued to embrace using the AERIAL smartphone app to monitor respiratory viral infections in real time, with 95% families using the app, 70% on a regular basis, resulting in the collection of 650 swabs from sick babies. The lead researcher on the AERIAL study is Dr Liz Starcevich.

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Making headlines about the health impacts of e-cigarettes Associate Professor Alex Larcombe’s leading program of research into what’s in e-cigarette products including nicotine in some, as well as other toxic chemicals and substances – has been referenced multiple times throughout the year in mainstream media stories, social media mentions and citations. Associate Professor Larcombe has also directly participated in a range of media interviews, to educate the public about the dangers of vaping. This research work has had a massive and rapid impact on how e-cigarettes are viewed from a health effects of exposure perspective, helping to reinforce the message that e-cigarettes are not harmless, and to inform policy.

Great minds came together at Wal-yan Scientific Retreat Wal-yan Centre team members and special guests travelled to Wadjemup (Rottnest) in October to spend an intensive two days together learning about, and providing input into, the broad range of research projects underway within the Centre.

Vertex grants to support advances in cystic fibrosis care Three outstanding researchers - Dr Daniel Laucirica, Dr KakMing Ling and Dr Samuel Montgomery - were awarded Vertex Cystic Fibrosis (CF) Mentored Innovation Research Awards. Together, Dr Laucirica, Dr Ling and Dr Montgomery received $540,000 funding to support their innovative and collaborative clinical research to improve the care of people with CF. Dr Laucirica’s project will specifically assess whether phages (viruses that kill bacteria) can be used as an anti-inflammatory therapy targeting neutrophils in the lungs during infection.

Dr Ling’s research project will yield important data for the future use of phage therapy in individuals with CF. This information will focus on the effectiveness of phages, how they are administered, and the various formulations available. Dr Montgomery’s research study aims to improve the lung health of young children with CF following a viral infection. Read more about Dr Ling’s and Dr Montgomery’s research Learn more about Dr Laucirica’s research

Community Involvement and Engagement

The scientific retreat also provided a forum to discuss future collaborations, new ideas and opportunities, and ways to improve the Centre’s research work. Read the full story here

At the Wal-yan Centre, we prioritise amplifying the community’s voice in respiratory research. Our unwavering commitment lies in ensuring that our research is not only relevant, but also delivers high-quality outcomes and successful translation of our research findings into effective clinical care. As part of this commitment we are proud to have over 50 community members who contribute to our research through our eight community reference groups: • BREATH (Building Respiratory Equity for Aboriginal and Torres Strait Islander Health) Consumer Reference Group of WA • Child and Adolescent Cystic Fibrosis Consumer Reference Group of WA

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• MAP (Metabolomics to predict asthma in children) Consumer Reference Group • Neuromuscular Consumer Reference Group • Next Generation CF Youth Consumer Reference Group • Paediatric Bronchiectasis Consumer Reference Group of Western Australia • Preterm Community Reference Group • Western Australian Epithelial Research Program (WAERP) Consumer Reference Group In addition, we are fortunate to have a number of community members who help to shape our research as ‘research buddies’ and as research investigators.

Community Involvement and Engagement (cont) Other community involvement highlights this year include: • A special evening where supporters of the Wal-yan Centre came together to learn about some of the Centre’s research underway in the areas of phage therapy, e-cigarettes and heated tobacco products, asthma, and lung health following preterm birth. Rael Rivers, who herself has asthma, as do her three children, also delivered a heartfelt presentation on ‘Why she wants change’.

• Completion of a preterm lung health priority setting partnership where the community were invited to work together with the Children’s Lung Health team to establish the community’s top 10 research priorities for the lung health of people born prematurely.

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During the period 1 July 2022 to 30 June 2023, the Centre’s organic Facebook posts reached 29,786 people and the number of followers increased to 580. The Centre’s tweets appeared on user’s screens (impressions) over 114,000 times, with the number of Twitter followers increasing to 350. Coverage of the Centre’s work has also been included on partner social media channels, including Telethon Kids Institute, Perth Children’s Hospital Foundation and Perth Children’s Hospital.

• Presentations at Cystic Fibrosis WA events and involvement in the organisation’s fundraising events including 65 Roses Day and the Matagarup Bridge Climb for Cystic Fibrosis • Associate Professor Anthony Kicic featured as the guest medical speaker at the Conquer Cystic Fibrosis ball, Professor Stephen Stick was interviewed for the special video presentation on the evening and Alana Harper braved the chilly waters of the Swan River, to swim one kilometre as part of the Dare to Care Swim for Conquer Cystic Fibrosis.

Through the Centre’s website, social media channels Twitter and Facebook - and mainstream media coverage, engagement with the community has increased.

There were 7,837 unique page views to the Wal-yan Centre website during the year and 30 news stories were published. • Consumer representatives embedded into the Centre’s governance committee - the Wal-yan Centre Scientific Steering Committee – and on award review and selection panels.

Relevant stories continued to be pitched to traditional media outlets and specialist publications, with coverage being achieved on many occasions during this time period.

• Wal-yan researchers volunteered to share their science through the Telethon Kids Institute’s outreach and education program

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Global Reach and Impact To achieve a strong global collaboration, we work in partnership with world-class researchers, clinicians and investigators, and participate in respiratory conferences and networks globally. International conferences we presented at during the year include: - American Thoracic Society, Washington DC - Australian Pacific Respiratory Society, Japan - International Congress of Antimicrobial Chemotherapy, Perth, Australia - North American Cystic Fibrosis Conference, Philadelphia, USA

- Research collaborations with: • Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique • Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid • Dalhousie University, Halifax, Canada • Department of Clinical Science, University of Bergen, Bergen, Norway • Department of Pediatrics, University of Wisconsin - Madison, Madison, WI, USA

- The European Respiratory Society (ERS) International Congress, Barcelona, Spain

• Department of ENT, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark

- The International Meeting on Indigenous Child Health in Tulsa, Oklahoma

• Erasmus University Medical Center, Rotterdam, Netherlands

- The Thoracic Society of Australia and New Zealand and The Australia and New Zealand Society of Respiratory Science (TSANZSRS) Annual Scientific Meeting, Christchurch, New Zealand

• Emory university, Georgia, USA

We are actively collaborating with colleagues and organisations around the world including:

• ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain

- Prematurity’s Effects on the Lungs in Children and Adults Network (PELICAN) - the European Respiratory Society’s fourth clinical research collaboration. Associate Professor Shannon Simpson co-chairs the consortium alongside Dr Jenny Hallberg from the Karolinska Institute, Sweden.

• King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

• ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain • INSERM, Paris, France

• Meyer Children’s Hospital, Florence, Italy • Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, Barcelona, Spain • Respiratory Medicine, University College London, London, UK • Research Institute, Hospital for Sick Children, Toronto, Canada • School of Medicine at Pontificia Universidad Católica de Chile • School of Medicine, Cardiff University, Cardiff, Wales

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• Seattle Children’s Research Institute, Seattle, WA, USA • The Bixby Center for Population, Health and Sustainability, School of Public Health, University of California, Berkeley, California, USA • Thirona, Nijmegen, The Netherlands • University of British Columbia, Canada • University of North Carolina at Chapel Hill School of Medicine, NC, USA

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• University of Manchester, UK • University of Bern, Bern, Switzerland • University of Washington, Seattle, WA, USA • University Health Network and University of Toronto, Canada • Yamagata Prefectural Central Hospital, Yamagata, Japan

Seed funding awarded to support three bold research ideas Attention-grabbing seed funding pitches were delivered by six researchers aiming to secure $20,000 in funding to help progress their bold ideas to the next stage.

Funding and developing our researchers The Wal-yan Centre is committed to supporting current and the next generation of respiratory researchers. This is being achieved through investing in our people and their ideas by providing funding opportunities for high quality research. Some funds also provide opportunity for new ideas and new research partnerships to grow ideas, and often results in further funding. Seven innovative lung health research projects announced as the 2023 Wal-yan Centre Strategic Inspiration Projects

The winners Michelle Schwager (left), Jane Choi (centre) and Renee Ng (absent from image), and Melinda Judge (right), award-winning ideas included:

Valued at a total of $1.99 million, the successful projects are looking at:

• investigating why some children with acute wheeze have an increased risk of recurrent asthma exacerbation

• accelerating an innovative, patented, therapeutic avenue to treat childhood wheezing and asthma using a new class of drugs that enhance airway epithelial repair Team Lead - Dr Thomas Iosifidis

• a creative approach to phage therapy, and • the effects of environmental factors on the respiratory health of Australian children.

• clearly defining the impact of climate change on children’s respiratory health in Australia – Team Lead - Professor Peter Le Souëf • if the way our immune system develops before birth is similar to how it functions in our respiratory system when we are older – Team Lead - Professor Stephen Stick • analysing the inhalable aerosols produced by e-cigarettes and relating the outcomes directly to the resultant health risks – Team Lead - Associate Professor Alex Larcombe

Seven innovative lung health research projects received funding support as the 2023 Wal-yan Respiratory Research Centre Strategic Inspiration Projects. The projects align to the purpose of the Centre - to undertake innovative, transformative work where teams come together to create significant impact and value to our community.

• development of a clinical program to implement bacteriophage (phage) therapy for bacterial infections that are resistant to antibiotics – Team Lead Associate Professor Anthony Kicic

Five innovative research projects supported by Inspiration Awards 2022

• working in partnership with First Nations communities throughout WA and wider Australia, local State and Aboriginal health services to reduce the significant Indigenous health gap in relation to respiratory disease – Team Lead Professor André Schultz

The Inspiration Awards are designed to support new and exciting projects that do not fit the traditional grant schemes.

• whether azithromycin - a commonly used antibiotic – is a safe, simple and affordable intervention to prevent severe early life acute respiratory infections in those born very preterm – Team Lead Associate Professor Shannon Simpson All supported projects set out to make significant impact within the Centre’s six strategic research areas. Importantly, they all provide the opportunity for collaboration and involvement from researchers across the Centre.

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Valued at $440,000, the Wal-yan Centre Inspiration Awards 2022 supported five cuttingedge research projects.

The five successful research projects are focussing on: • development of a mix-and-read assay (laboratory test) for detecting multiple viruses and bacteria in just minutes – Chief Investigator Patricia Agudelo-Romero • testing whether clusters exist in the blood immune cells collected from children during wheezing and asthma, to guide early identification and treatment of children at high-risk of developing persistent respiratory exacerbations – Chief Investigator Laura Coleman

Wal-yan Respiratory Research Centre Annual Report 2023 Page 23

• development of software that can automatically analyse the data generated by the wearable electrical impedance tomography belt – a tool used to monitor lung function in real time – Chief Investigator Yuliya Karpievitch • understanding how allergies interfere with the immune system’s ability to fight viruses in children and contribute to asthma development Chief Investigator Jonatan Leffler • establishing how climate change has altered Aboriginal child health over the last 30 years, with the aim of using this information to help protect Aboriginal children from future environmental health risks – Chief Investigator Peter Le Souef

Prizes, Awards and Positions

Funding and developing our researchers (cont)

• A/Prof Shannon Simpson was one of National Health and Medical Research Council’s ‘Ten of the Best’ which highlights outstanding Australian research • A/Prof Shannon Simpson was awarded a Stan Perron Charitable Foundation People grant • A/Prof Shannon Simpson featured in a Herald Sun article as one of Australia’s top female scientists changing the world • Dr Samuel Montgomery received the Thoracic Society of Australia and New Zealand (TSANZ) Janet Elder International Travel Award in the early career researcher category • A/Prof Anthony Kicic was awarded 2022 PhD Supervisor of the Year at Telethon Kids Institute • Dr Elizabeth Smith was awarded a European Respiratory Society (ERS) Young Scientist Sponsorship

Wal-yan Centre scholarship awardees to research interventions for improving lung health As part of the Wal-yan Centre’s aim to support the next generation of scientists in children’s respiratory research, a competitive scholarship program was introduced. The successful candidates, Michael Beaven (pictured middle) and Sourav Shyam (pictured left), and Yaqin Alziyadat (right), will receive three years of funding to support their PhD completion. Michael’s PhD is focussed on understanding how the body of an adult who was born preterm responds to incremental exercise, and how this response changes over time compared to adults who were born at term.

Yaqin is looking at how modifying the body’s immune system using a bacterial lysate (medicine made from bacterial cells that are broken down) can redirect the way the immune system reacts to viral respiratory infections in young children, towards more natural responses and away from those that lead to wheeze and asthma.

• Dr Patricia Agudelo-Romero was appointed as a member of the European Virus Bioinformatics Center • Grace Pettigrew was awarded a European Lung Foundation Travel Grant for Best Abstract in Patient Centred Research for the ERS International Congress • Grace Pettigrew was awarded a Thoracic Society of Australia and New Zealand and The Australia and New Zealand Society of Respiratory Science (TSANZSRS) Annual Scientific Meeting (ASM) 2023 Travel Grant • Tiffany Bradshaw was awarded a TSANZSRS ASM 2023 Travel Grant • Talya Conradie, was awarded the best talk at the November Microbiome Virtual International Forum

• Denby Evans was awarded the Ann Woolcock New Investigator Award • Denby Evans was awarded the Stan and Jean Perron Excellence Award • Renee Ng was awarded the American Society for Microbiology Best Oral Presentation Award, and the International Society of Antimicrobial Chemotherapy Young Investigator Travel Award at the International Congress of Antimicrobial Chemotherapy • Andrew Vaitekenas was one of six finalists for the Ann Woolcock New Investigator Award • Josh Iszatt was awarded first prize in the Wal-yan Centre New Investigator presentations • Rebecca Watkinson was awarded second place in the Wal-yan Centre New Investigator presentations • Dr Katherine Landwehr achieved a chancellor’s commendation at her doctorate graduation • Daniel Laucirica passed his PhD thesis • Laura Coleman submitted her PhD thesis • Jane Choi submitted her PhD thesis • Renee Ng Submitted her PhD thesis • Alex de Bont passed his Masters course • Honours student Julia Casella passed her course • Honours student Ashleigh Heng-Chin passed her course • Honours student Jake Puglia passed his course • Honours student Braeden Simms passed his course

Sourav’s PhD is focussed on whether therapeutics and drugs can improve lung health. If the answer to this is yes, Sourav’s study aims to streamline what drugs and therapies would help improve patients’ airways.

Wal-yan Respiratory Research Centre Annual Report 2023 Page 24

Honours and PhD Student Highlights

Wal-yan Respiratory Research Centre Annual Report 2023 Page 25

Published papers 1.

Anagnostopoulou P, Latzin P, Jensen R, Stahl M, Harper A, Yammine S, Usemann J, Foong RE, Spycher B, Hall GL, Singer F, Stanojevic S, Mall MA, Ratjen F, Ramsey KA. Normative data for multiple breath washout outcomes in school-aged Caucasian children. Eur Respir J. 2022;60(2)

Ariff A, Song Y, Aguilar R, …… Khoo SK, Wiertsema S, Bassat Q, …… Laing IA, Guinovart C, ……. Le Souëf P, Zhang G. Genetic variants of TLR4, including the novel variant, rs5030719, and related genes are associated with susceptibility to clinical malaria in African children. Malar J. 2023;22(1)

13.

Chen Y, Lv Q, Andrinopoulou ER, ……. Caudri D, Davis SD, Rosenfeld M, ……. Stick S, Tiddens HAWM. Automatic bronchus and artery analysis on chest computed tomography to evaluate the effect of inhaled hypertonic saline in children aged 3-6 years with cystic fibrosis in a randomized clinical trial. J Cyst Fibrosis. 2023

14.

Corin Willers C, Frauchiger BS, Stranzinger E, …… Ramsey KA. Feasibility of unsedated lung MRI in young children with cystic fibrosis. Eur Respir J. 2022;60(5)

15.

Dahl MJ, Lavizzari A, Davis JW, Noble PB, Dellacà R, Pillow JJ. Impact of fetal treatments for congenital diaphragmatic hernia on lung development. Anat Rec. 2022

16.

De Luca D, Tingay DG, Van Kaam AH, Courtney SE, ……… Pillow JJ, Van Tuijl M, Carnielli VP, et al for the Neonatal ARDS Project Collaboration Group. Epidemiology of Neonatal Acute Respiratory Distress Syndrome: Prospective, Multicenter, International Cohort Study. Pediatr Crit Care Med. 2022;23(7):524-34.

17.

Depiazzi J, Bourke C, Stick S, Withers A. Prevalence of tracheobronchomalacia is higher than previously reported in children with cystic fibrosis. Pediatr Pulmonol. 2023

18.

Donovan GM, Wang KCW, Elliot JG, James AL, Noble PB. Quantifying airway remodelling for research or clinical purposes: How should we normalize for airway size? Respirology. 2023

Atshan SS, Hamat RA, Aljaberi MA, …….. Kicic A. Phage Therapy as an Alternative Treatment Modality for Resistant Staphylococcus aureus Infections. Antibiotics. 2023;12(2)

19.

Evans DJ, Pillow JJ, Simpson SJ, Kicic A. Living with lung disease: experimental models to assess the long-term effects of prematurity. Am J Physiol Lung Cell Mol Physiol. 2022;323(5):L503-L14.

Bakker C, Chivers E, Chia XW, Quintrell E, Wyrwoll C, Larcombe A. Switching from tobacco cigarettes in very early pregnancy: The effects of in utero e-cigarette exposure on mouse offspring neurodevelopment and behaviour. Physiol Behav. 2023;263

20.

Fabri L, Shanthikumar S, Tadd K, Morgan L, Schultz A, Robinson P. Fissure adjacent partial lobe atelectasis in primary ciliary dyskinesia. J Paediatr Child Health. 2022;58(4):683-6.

21.

Bhakta NR, Kaminsky DA, Bime C, Thakur N, Hall GL, McCormack MC, Stanojevic S. Addressing Race in Pulmonary Function Testing by Aligning Intent and Evidence With Practice and Perception. Chest. 2022;161(1):288-97.

Fernando DT, Bhatt R, Saiganesh A, Schultz A, Gera P. Lung abscess: 14 years of experience in a tertiary paediatric hospital. ANZ J Surg. 2022;92(7-8):1850-5.

22.

Bowatte G, Bui DS, Priyankara S, ……. Martino D, Holloway JW, Svanes C, et al. Parental preconception BMI trajectories from childhood to adolescence and asthma in the future offspring. J Allergy Clin Immunol. 2022

Foong RE, Franklin P, Sanna F, Hall GL, Sly PD, Thorstensen EB, Doherty DA, Keelan JA, Hart RJ. Longitudinal effects of prenatal exposure to plastic-derived chemicals and their metabolites on asthma and lung function from childhood into adulthood. Respirology. 2023;28(3):236-46.

23.

Caparrós-Martín JA, Saladie M, Agudelo-Romero SP, Reen FJ, Ware RS, Sly PD, Stick SM, O’Gara F, for the COMBAT Study Group. Detection of bile acids in bronchoalveolar lavage fluid defines the inflammatory and microbial landscape of the lower airways in infants with cystic fibrosis. Microbiome. 2023;11(1)

Freislich Z, Stoecklin B, Hemy N, Pillow JJ, Hall GL, Wilson AC, Simpson SJ. The ventilatory response to hypoxia is blunted in some preterm infants during the second year of life. Front Pediatr. 2022;10

24.

Gill FJ, Cooper AL, Laird P, Leslie GD. Aboriginal perspectives on recognising clinical deterioration in their child and communicating concerns to clinicians. J Pediatr Nurs. 2022;63:e10-e7.

25.

Gwatimba A, Ho J, Iosifidis T, Karpievitch YV. Rainbow: Automated Air-Liquid Interface Cell Culture Analysis Using Deep Optical Flow. Journal of Open Source Software. 2022;7(71):4080.

26.

Gwatimba A, Rosenow T, Stick SM, Kicic A, Iosifidis T, Karpievitch YV. AI-Driven Cell Tracking to Enable High-Throughput Drug Screening Targeting Airway Epithelial Repair for Children with Asthma. J Pers Med. 2022;12(5)

27.

Chang AB, Morgan LC, Duncan EL, ……. Schultz A, Leo PJ, McCallum GB, et al. Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, doubledummy, 2×2 partial factorial, randomised controlled trial. BMJ Open Respir Res. 2022;9(1)

Hemstock EJ, Foong RE, Hall GL, Wheeler AJ, Dharmage SC, et al. No association between in utero exposure to emissions from a coalmine fire and post-natal lung function. BMC Pulm Med. 2023;23(1)

28.

11.

Chapman L, Larcombe AN, Lim E (2022) The evidence on e-cigarettes is clear. Medicus. 62(4):13.

Ho RM, Bowen AC, Blyth CC, Imrie A, Kollmann TR, Stick SM, Kicic A. Defining the pediatric response to SARS-CoV-2 variants Front Immunol. 2023 May 25;14:1200456. doi: 10.3389/ fimmu.2023.1200456. eCollection 2023.

29.

12.

Chaya S, Macginty R, Jacobs C, Githinji L, Hlengwa S, Simpson SJ, Zar HJ, Hantos Z, Gray DM. Normal values of respiratory oscillometry in South African children and adolescents. ERJ Open Res. 2023;9(2)

Hufsky F, Abecasis A, Agudelo-Romero P, Bletsa M, Brown K, et al. Women in the European Virus Bioinformatics Center. Viruses. 2022;14(7)

30.

Iszatt JJ, Larcombe AN, Garratt LW, Stick SM, Agudelo-Romero P, Kicic A, for the WAERP and Arest CF Study Groups. Genome Sequences of Two Lytic Staphylococcus aureus Bacteriophages Isolated from Wastewater. Micro Res Ann. 2022;11(12)

Caudri D, Turkovic L, de Klerk NH, Rosenow T, Murray CP, Steyerberg EW, Ranganathan SC, Sly P, Stick SM, Breuer O, for the AREST CF Study Group. A screening tool to identify risk for bronchiectasis progression in children with cystic fibrosis. Pediatr Pulmonol. 2022;57(1):122-31.

Chang AB, Bell SC, Byrnes CA, …….. Laird P, Mooney S, Morgan L, et al. Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand. Respirology. 2023;28(4):339-49.

10.

Wal-yan Respiratory Research Centre Annual Report 2023 Page 26

Wal-yan Respiratory Research Centre Annual Report 2023 Page 27

Published papers (cont) 31.

Iszatt JJ, Larcombe AN, Garratt LW, Trend S, Stick SM, Agudelo-Romero P, Kicic A. Genome Sequence of a Lytic Staphylococcus aureus Bacteriophage Isolated from Breast Milk. Micro Res Ann. 2022;11(12)

46.

Landwehr KR, Nabi MN, Rasul MG, Kicic A, Mullins BJ. Biodiesel Exhaust Toxicity with and without Diethylene Glycol Dimethyl Ether Fuel Additive in Primary Airway Epithelial Cells Grown at the Air-Liquid Interface. Environ Sci Technol. 2022;56(20):14640-8.

32.

Kaminsky DA, Simpson SJ, Berger KI, Calverley P, ……. Hall GL, Ioan I, Irvin CG, et al. Clinical significance and applications of oscillometry. Eur Respir Rev. 2022;31(163)

47.

Larcombe A. Dispelling misconceptions about who uses e-cigarettes and why. Med J Aust. 2023

33.

Kelada L, Wakefield C, Vidic N, Armstrong DS, …….. Schultz A, Selvadurai H, Tai A, Jaffe A. Genomic testing for children with interstitial and diffuse lung disease (chILD): parent satisfaction, understanding and health-related quality of life. BMJ Open Respir Res. 2022;9(1)

48.

Larcombe A, Allard S, Mullins B. Chemical analysis of fresh and aged Australian e-cigarette liquids. Med J Aust. 2022

34.

Kentgens AC, Latzin P, Anagnostopoulou P, ……. Harper A, Yammine S, Foong RE, Hall GL, Singer F, ……. Ramsey KA. Normative multiple-breath washout data in school-aged children corrected for sensor error. Eur Respir J. 2022;60(2)

49.

Larcombe A, Chapman D, Ween M. What doctors should consider before prescribing e-liquids for e-cigarettes. Med J Aust. 2022

50.

Larcombe AN, Chivers EK, Huxley RR, Musk AW, Franklin PJ, Mullins BJ. Electronic Cigarette Usage Patterns and Perceptions in Adult Australians. Toxics. 2023;11(3)

51.

Larcombe AN, Iosifidis T, Foong RE, Berry LJ, Stumbles PA, Strickland DH, Sly PD, Kicic A. Exacerbation of chronic cigarette-smoke induced lung disease by rhinovirus in mice. Respir Physiol Neurobiol. 2022;298:103846.

52.

Lau GTY, Laird P, Stevenson PG, Schultz A. Frequency of protracted bacterial bronchitis and management pre-respiratory referral. J Paediatr Child Health. 2022;58(1):97-103.

53.

Laucirica DR, Schofield CJ, McLean SA, Margaroli C, Agudelo-Romero P, Stick SM, Tirouvanziam R, Kicic A, Garratt LW, for the Western Australian Epithelial Research Program and Australian Respiratory Early Surveillance Team for CF. Pseudomonas aeruginosa modulates neutrophil granule exocytosis in an in vitro model of airway infection. Immunol Cell Biol. 2022;100(5):35270.

54.

Laucirica DR, Stick SM, Garratt LW, Kicic A. Bacteriophage: A new therapeutic player to combat neutrophilic inflammation in chronic airway diseases. Front Med. 2022;9

55.

Laird P, Ball N, Brahim S, Brown H, Chang AB, Cooper M, Cox D, Cox D, Crute S, Foong RE, Isaacs J, Jacky J, Lau G, McKinnon E, Scanlon A, Smith EF, Thomason S, Walker R, Schultz A. Prevalence of chronic respiratory diseases in Aboriginal children: A whole population study. Pediatr Pulmonol. 2022;57(12):3136-44.

Ling KM, Stick SM, Kicic A. Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes? Front Med (Lausanne). 2023 May 17;10:1088494. doi: 10.3389/fmed.2023.1088494. eCollection 2023

56.

40.

Laird P, Burr C, Gill FJ, Schultz A. Spring-infusors: How a simple and small solution can create king-sized complexity. Nurs Open. 2023;10(2):1125-34.

Liu J, Bowatte G, Pham J, Perret JL, ……. Martino D, Mishra GD, Abramson MJ, et al. Prepubertal smoke exposure of fathers and increased risk of offspring asthma: a possible transgenerational effect. Eur Respir J. 2022;60(4)

57.

41.

Laird PJ, Chang AB, Walker R, Barwick M, Whitby J, Cooper MN, Gill F, McKinnon E, Schultz A. Evaluation of the implementation and clinical effects of an intervention to improve medical follow-up and health outcomes for Aboriginal children hospitalised with chest infections. Lancet Reg Health West Pac. 2023

Mann TS, Larcombe AN, Wang KCW, Shamsuddin D, Landwehr KR, Noble PB, Henry PJ. Azithromycin inhibits mucin secretion, mucous metaplasia, airway inflammation, and airways hyperresponsiveness in mice exposed to house dust mite extract. Am J Physiol Lung Cell Mol Physiol. 2022;322(5):L683-L98.

58.

Margaroli C, Horati H, Garratt LW, Giacalone VD, Schofield C, Dittrich AS, Rosenow T, Dobosh BS, ……. Kicic A, Guglani L, Stick SM, Janssens HM, Tirouvanziam R. Macrophage PD-1 associates with neutrophilia and reduced bacterial killing in early cystic fibrosis airway disease. J Cyst Fibrosis. 2022

59.

Markovetz MR, Garbarine IC, Morrison CB, ……. Stick SM, Ehre C, Boucher RC, et al. Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis. J Cyst Fibrosis. 2022

60.

Marpole R, Ohn M, O’Dea CA, von Ungern-Sternberg BS. Clinical utility of preoperative pulmonary function testing in pediatrics. Paediatr Anaesth. 2022;32(2):191-201.

61.

Marpole R, Wilson AC. Benefits of reviewing pancreatic function in children with cystic fibrosis. Pediatr Pulmonol. 2022;57(6):1537-9.

35.

Kicic-Starcevich E, Hancock DG, Iosifidis T, Agudelo-Romero P, Caparros-Martin JA, Silva D, Turkovic L, Le Souef PN, Bosco A, Martino DJ, Kicic A, Prescott SL, Stick SM. Airway Epithelium Respiratory Illnesses and Allergy (AERIAL) birth cohort: study protocol medRxiv. 2023 May 3:2023.04.29.23289314. doi: 10.1101/2023.04.29.23289314. Preprint.PMID: 37205501

36.

Keszler M, Pillow JJ, Courtney SE. High-frequency ventilation. Goldsmith’s Assisted Ventilation of the Neonate: An Evidence-Based Approach to Newborn Respiratory Care, Seventh Edition: Elsevier; 2022. p. 269-87.

37.

Khatami A, Foley DA, Warner MS, Barnes EH, Peleg AY, Li J, Stick S, Burke N, Lin RCY, Warning J, Snelling TL, Tong SYC, Iredell J. Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial. BMJ Open. 2022;12(12)

38.

Kotecha SJ, Gibbons JTD, Course CW, Evans EE, Simpson SJ, Watkins WJ, Kotecha S. Geographical Differences and Temporal Improvements in Forced Expiratory Volume in 1 Second of Preterm-Born Children: A Systematic Review and Meta-analysis. JAMA Pediatr. 2022

39.

42.

Laird PJ, Walker R, McCallum G, …….. Cooper M, Norman R, Patel B, Lau G, Chang AB, Schultz A. Change in health outcomes for First Nations children with chronic wet cough: rationale and study protocol for a multi-centre implementation science study. BMC Pulm Med. 2022;22(1)

43.

Landwehr KR, Hillas J, Mead-Hunter R, King A, O’Leary RA, Kicic A, Mullins BJ, Larcombe AN, for the WAERP Study Group. Toxicity of different biodiesel exhausts in primary human airway epithelial cells grown at air-liquid interface. Sci Total Environ. 2022;832

44.

Landwehr KR, Hillas J, Mead-Hunter R, King A, O’Leary RA, Kicic A, Mullins BJ, Larcombe AN, for the WAERP Study Group. Biodiesel feedstock determines exhaust toxicity in 20% biodiesel: 80% mineral diesel blends. Chemosphere. 2023;310

45.

Landwehr KR, Mead-Hunter R, O’Leary RA, Kicic A, Mullins BJ, Larcombe AN. Respiratory Health Effects of In Vivo Sub-Chronic Diesel and Biodiesel Exhaust Exposure. Int J Mol Sci. 2023;24(6)

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Wal-yan Respiratory Research Centre Annual Report 2023 Page 29

Published papers (cont) 77.

Pinot de Moira A, Strandberg-Larsen K, ……. Foong RE, Haakma S, Harris JR, Huang RC, Inskip H, Lertxundi A, et al. Associations of early-life pet ownership with asthma and allergic sensitization: A meta-analysis of more than 77,000 children from the EU Child Cohort Network. J Allergy Clin Immunol. 2022

78.

Ramsey K. Arsenic and respiratory disease. Handbook of Arsenic Toxicology: Elsevier; 2023. p. 381-94.

79.

Ramsey KA, Schultz A. Monitoring disease progression in childhood bronchiectasis. Front Pediatr. 2022;10

80.

Read JF, Serralha M, Mok D, Holt B, Cruickshank M, Karpievitch YV, Broadhurst DI, Sly PD, Strickland DH, Reinke SN, Holt PG, Bosco A. Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life. Front Immunol. 2022;13

McLeod C, Wood J, Mulrennan S, Morey S, Schultz A, Messer M, Spaapen K, Wu Y, Mascaro S, Smyth AR, Blyth CC, Webb S, Snelling TL, Norman R. Preferred health outcome states following treatment for pulmonary exacerbations of cystic fibrosis. J Cyst Fibros. 2022

81.

Reyna ME, Dai R, Tran MM, ……. Foong RE, Emmerson M, ……. Hall GL, Moraes TJ, Sears MR, Subbarao P. Development of a Symptom-Based Tool for Screening of Children at High Risk of Preschool Asthma. JAMA Netw Open. 2022;5(10):e2234714.

67.

Mercier J, Calmel C, Mésinèle J, Sutanto E, Merabtene F, Longchampt E, Sage E, Kicic A, Boëlle PY, Corvol H, Ruffin M, Guillot L. SLC6A14 Impacts Cystic Fibrosis Lung Disease Severity via mTOR and Epithelial Repair Modulation. Front Mol Biosci. 2022;9

82.

Ruseckaite R, Salimi F, Earnest A, …….. Schultz A, Wainwright C, Ward N, Wark P, Ahern S. Survival of people with cystic fibrosis in Australia. Sci Rep. 2022;12(1)

68.

Mincham KT, Scott NM, Lauzon-Joset JF, Leffler J, Stumbles PA, Holt PG, Strickland DH. Early Life Ovalbumin Sensitization and Aerosol Challenge for the Induction of Allergic Airway Inflammation in a BALB/c Murine Model. Bio-Protoc. 2019;9(5)

83.

Sahih M, Schultz A, Wilson A, Alakeson R, Taylor E, Mullins B, Martin AC. Paediatric headbox as aerosol and droplet barrier. Arch Dis Child. 2022;107(1):65-7.

84.

Sanders DB, Deschamp AR, Hatch JE, Slaven JE, Gebregziabher N, Corput MKVD, Tiddens HAWM, Rosenow T, Storch GA, Hall GL, Stick SM, Ranganathan S, Ferkol TW, Davis SD. Association between early respiratory viral infections and structural lung disease in infants with cystic fibrosis. J Cyst Fibrosis. 2022;21(6):1020-6.

85.

Sanna F, Locatelli F, Sly PD, White E, Heyworth J, Blake D, Hall GL, Foong RE. Characterisation of lung function trajectories and associated early-life predictors in an Australian birth cohort study. ERJ Open Res. 2022;8(1)

86.

Savigni DL, Chang AY, Sorensen NL, Papagianis PC, Ahmadi-Noorbakhsh S, Pillow JJ, Noble PB. Airway smooth muscle thickness and contraction are enhanced by intraamniotic lipopolysaccharide in an ovine model of premature birth. J Appl Physiol (1985). 2022;133(4):959-69.

87.

Schultz A. Adherence to CF treatment can be improved with the right approach! Thorax. 2022;77(5):428.

88.

Schultz A, Barrett A, Balding E, Billingham W, Branch-Smith C, Grover Z, Yikilmaz G, Bourke C, Depiazzi J, Sander N, Foster J, Cooper M, Zepf F. A pilot study of disease related education and psychotherapeutic support for unresolved grief in parents of children with CF. Sci Rep. 2022;12(1)

89.

Schultz A, Chang AB, Gill F, Walker R, Barwick M, Munns S, Cooper MN, Norman R, Laird P. Implementation of a strategy to facilitate effective medical follow-up for Australian First Nations children hospitalised with lower respiratory tract infections: study protocol. BMC Pulm Med. 2022;22(1)

90.

Schultz A, McLeod C, Berry S, Marsh J, McKenzie A, Messer M, Wood J, Saville B, Jaffe A, Ranganathan S, Stick S, Wark P, Webb S, Snelling T. BEAT CF pulmonary exacerbations core protocol for evaluating the management of pulmonary exacerbations in people with cystic fibrosis. Trials. 2023;24(1)

91.

Shaw NC, Kicic A, Fletcher S, Wilton SD, Stick SM, Schultz A. Primary Nasal Epithelial Cells as a Surrogate Cell Culture Model for Type-II Alveolar Cells to Study ABCA-3 Deficiency. Front Med (Lausanne). 2022;9:827416.

62.

Martinovich KM, Kicic A, Stick SM, Johnsen RD, Fletcher S, Wilton SD. Investigating the Implications of CFTR Exon Skipping Using a Cftr Exon 9 Deleted Mouse Model. Front Pharmacol. 2022;13

63.

Mateus T, Seppanen EJ, de Gier C, Clark S, Coates H, Vijayasekaran S, Prosser K, Wiertsema SP, Fuery A, Kirkham LAS, Richmond PC, Thornton RB. Sleep Disordered Breathing and Recurrent Tonsillitis Are Associated With Polymicrobial Bacterial Biofilm Infections Suggesting a Role for Anti-Biofilm Therapies. Front Cell Infect Microbiol. 2022;12

64.

McKnight L, Schultz A, Vidic N, Palmer EE, Jaffe A. Learning to make a difference for chILD: Value creation through network collaboration and team science. Pediatr Pulmonol. 2023

65.

McLeod C, Smyth AR, Messer M, Schultz A, Wood J, Norman R, Blyth CC, Webb S, et al. Protocol for establishing a core outcome set for evaluation in studies of pulmonary exacerbations in people with cystic fibrosis. BMJ Open. 2022;12(9):e056528.

66.

69.

Mok LC, Garcia-Uceda A, Cooper MN, Kemner-Van De Corput M, Rosenow T, De Boeck K, Stick S, Tiddens HAWM. The effect of CFTR modulators on structural lung disease in cystic fibrosis. Front Pharmacol. 2023;14

70.

Mutlu S, Scalise M, Stumbles PA, Gazdhar A, Blank F. Allies or enemies? The effect of regulatory T cells and related T lymphocytes on the profibrotic environment in bleomycin-injured lung mouse models. Clin Exp Med. 2022

71.

Ng RN, Tai AS, Chang BJ, Stick SM, Agudelo-Romero P, Kicic A. Complete Genomes of Three Pseudomonas aeruginosa Bacteriophages, Kara-mokiny 1, Kara-mokiny 2, and Kara-mokiny 3. Micro Res Ann. 2022;11(12)

72.

Ngo CC, Massa HM, McMonagle BA, Perry CF, Nissen MD, Sloots TP, Thornton RB, Cripps AW. Predominant Bacterial and Viral Otopathogens Identified Within the Respiratory Tract and Middle Ear of Urban Australian Children Experiencing Otitis Media Are Diversely Distributed. Front Cell Infect Microbiol. 2022;12

73.

Parker E, Judge MA, Pastor L, ……. Carter KW, Anderson D, Mandomando I, Clifford HD, Naniche D, Le Souëf PN. Gene dysregulation in acute HIV-1 infection – early transcriptomic analysis reveals the crucial biological functions affected. Front Cell Infect Microbiol. 2023;13

74.

Patel D, Hall GL, Broadhurst D, Smith A, Schultz A, Foong RE. Does machine learning have a role in the prediction of asthma in children? Paediatr Respir Rev. 2022;41:51-60.

75.

Pattie P, Ranganathan S, Harrison J, Vidmar S, Hall GL, Foong RE, Harper A, Ramsey K, Wurzel D, for Arest CF. Quality of life is poorly correlated to lung disease severity in school-aged children with cystic fibrosis. J Cyst Fibrosis. 2022;21(3):e188-e203.

76.

Pettinari G, Finello J, Plaza Rojas M, ……. Agudelo-Romero P, Enet A, González C, Lascano R, Saavedra L. Autophagy modulates growth and development in the moss Physcomitrium patens. Front Plant Sci. 2022;13

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Wal-yan Respiratory Research Centre Annual Report 2023 Page 31

Published papers (cont) 92.

93.

Shein AMS, Wannigama DL, Higgins PG, Hurst C, Abe S, Hongsing P, Chantaravisoot N, Saethang T, Luk-In S, Liao T, Nilgate S, Rirerm U, Kueakulpattana N, Srisakul S, Aryukarn A, Laowansiri M, Hao LY, Yonpiam M, Ragupathi NKD, Techawiwattanaboon T, Ngamwongsatit N, Amarasiri M, Ounjai P, Kupwiwat R, Phattharapornjaroen P, Badavath VN, Leelahavanichkul A, Kicic A, Chatsuwan High prevalence of mgrB-mediated colistin resistance among carbapenem-resistant Klebsiella pneumoniae is associated with biofilm formation, and can be overcome by colistin-EDTA combination therapy. T.Sci Rep. 2022 Jul 28;12(1):12939. doi: 10.1038/s41598-022-17083-5.PMID: 35902639 Shrine N, Izquierdo AG, Chen J, Packer R, …….. Foong RE, Harris SE, Taylor A, ……. Hall GL, Gauderman WJ, Brightling C, et al. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Nat Genet. 2023;55(3):410-22.

94.

Smith EF, Hemy NR, Hall GL, Wilson AC, Murray CP, Simpson SJ. Risk factors for poorer respiratory outcomes in adolescents and young adults born preterm. Thorax. 2023

95.

Stanojevic S, Kaminsky DA, …….. Hall GL, Hallstrand TS, Leuppi JD, MacIntyre N, McCormack M, Rosenfeld M, Swenson ER. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J. 2022;60(1)

96.

Stick SM, Foti A, Ware RS, Tiddens H, Clements BS, Armstrong DS, et al for the Combat CF Study Group CCS. The effect of azithromycin on structural lung disease in infants with cystic fibrosis (COMBAT CF): a phase 3, randomised, double-blind, placebo-controlled clinical trial. Lancet Respir Med. 2022;10(8):776-84.

97.

Stoecklin B, Choi YJ, Dassios T, Jones JG, Lockwood GG, Pillow JJ. Unstable SpO2 in preterm infants: The key role of reduced ventilation to perfusion ratio. Front Physiol. 2023;14

98.

Temple SEL, Ho G, Bennetts B, ……. Schultz A, Gayagay T, Roscioli T, et al. The role of exome sequencing in childhood interstitial or diffuse lung disease. Orphanet J Rare Dis. 2022;17(1)

99.

Tiddens HAWM, Chen Y, Andrinopoulou ER, …….. Stick SM, Anthony MM, Au J, ……. Clements B, Cooper P, Davis SD, …….. Foti A, Gan R, et al for the SHIP-CT Study Group. The effect of inhaled hypertonic saline on lung structure in children aged 3–6 years with cystic fibrosis (SHIP-CT): a multicentre, randomised, double-blind, controlled trial. Lancet Respir Med. 2022;10(7):669-78.

100. Troy NM, Strickland D, Serralha M, de Jong E, Jones AC, Read J, Galbraith S, Islam Z, Kaur P, Mincham KT, Holt BJ, Sly PD, Bosco A, Holt PG. Protection against severe infant lower respiratory tract infections by immune training: Mechanistic studies. J Allergy Clin Immunol. 2022;150(1):93103. 101. Tu X, Gomez HM, Kim RY, Brown AC, de Jong E, Galvao I, Faiz A, Bosco A, Horvat JC, Hansbro P, Donovan C. Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma. Respir Res. 2023;24(1) 102. Tu X, Kim RY, Brown AC, de Jong E, Jones-Freeman B, Ali MK, Gomez HM, Budden KF, Starkey MR, Cameron GJM, Loering S, Nguyen DH, Nair PM, Haw TJ, Alemao CA, Faiz A, Tay HL, Wark PAB, Knight DA, Foster PS, Bosco A, Horvat JC, Hansbro PM, Donovan C. Airway and parenchymal transcriptomics in a novel model of asthma and COPD overlap. J Allergy Clin Immunol. 2022

104. Vaitekenas A, Tai AS, Ramsay JP, Stick SM, Agudelo-Romero P, Kicic A. Complete Genome Sequences of Four Pseudomonas aeruginosa Bacteriophages: Kara-mokiny 8, Kara-mokiny 13, Kara-mokiny 16, and Boorn-mokiny 1. Micro Res Ann. 2022;11(12) 105. Wang CJ, Noble PB, Elliot JG, Choi YS, James AL, Wang KCW. Distribution, composition, and activity of airway-associated adipose tissue in the porcine lung. Am J Physiol Lung Cell Mol Physiol. 2023;324(2):L179-L89. 106. Wang CJ, Noble PB, Elliot JG, James AL, Wang KCW. From Beneath the Skin to the Airway Wall: Understanding the Pathological Role of Adipose Tissue in Comorbid Asthma-Obesity. Compr Physiol. 2023;13(1):4321-53. 107. Wang KCW, Donovan GM, Saglani S, Mauad T, James AL, Elliot JG, Noble PB. Growth of the airway smooth muscle layer from late gestation to childhood is mediated initially by hypertrophy and subsequently hyperplasia. Respirology. 2022 108. Wang KCW, Foong RE. Editorial: The contributions of women to respiratory physiology and pathophysiology. Front Physiol. 2023;14 109. Wang KCW, James AL. Small for gestational age at term and adult lung function. Respirology. 2022 110. Wannigama DL, Amarasiri M, Hongsing P, Hurst C, Modchang C, Chadsuthi S, Anupong S, Phattharapornjaroen P, Rad S M AH, Fernandez S, Huang AT, Vatanaprasan P, Jay DJ, Saethang T, Luk-In S, Storer RJ, Ounjai P, Devanga Ragupathi NK, Kanthawee P, Sano D, Furukawa T, Sei K, Leelahavanichkul A, Kanjanabuch T, Hirankarn N, Higgins PG, Kicic A, Singer AC, Chatsuwan T, Trowsdale S, Abe S, McLellan AD, Ishikawa H. COVID-19 monitoring with sparse sampling of sewered and non-sewered wastewater in urban and rural communities iScience. 2023 Jul 21;26(7):107019. doi: 10.1016/j.isci.2023.107019. Epub 2023 Jun 9. 111. Wijs LA, Doherty DA, Keelan JA, ……. Hall GL, Sly PD, Holt PG, Hart RJ. Asthma and allergies in a cohort of adolescents conceived with ART. Reprod BioMed Online. 2022;45(6):1255-65. 112. Withers A, Maul J, Rosenheim E, O’Donnell A, Wilson A, Stick S. Comparison of home ambulatory type 2 polysomnography with a portable monitoring device and in-laboratory type 1 polysomnography for the diagnosis of obstructive sleep apnea in children. J Clin Sleep Med. 2022;18(2):393-402. 113. Withers PC, Cooper CE, Larcombe AN. Relative Water Economy Is a Useful Index of Aridity Tolerance for Australian Poephiline Finches. Birds. 2022;3(2):172-83. 114. Wyrwoll CS, Papini MG, Chivers EK, Yuan J, Pavlos NJ, Lucas RM, Bierwirth PN, Larcombe AN. Long-term exposure of mice to 890 ppm atmospheric CO2 alters growth trajectories and elicits hyperactive behaviours in young adulthood. J Physiol. 2022;600(6):1439-53. 115. Zannin E, Stoecklin B, Choi JY, Simpson SJ, Veneroni C, Dellaca RL, Pillow JJ. Ventilatory response and stability of oxygen saturation during a hypoxic challenge in very preterm infants. Pediatr Pulmonol. 2023;58(5):1454-62. 116. Zhu Y, Chew KY, Wu M, ……. Kollmann TR, Martino D, Joensuu M, Meunier FA, Balistreri G, Bielefeldt-Ohmann H, Bowen AC, Kicic A, Sly PD, Spann KM, Short KR. Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells. PloS Biol. 2022;20(8):e3001728.

103. Urs R, Stoecklin B, Pillow JJ, Hartmann B, Hall GL, Simpson SJ. Collecting exhaled breath condensate from non-ventilated preterm-born infants: a modified method. Pediatr Res. 2022;91(4):717-9.

Wal-yan Respiratory Research Centre Annual Report 2023 Page 32

Wal-yan Respiratory Research Centre Annual Report 2023 Page 33

Grant Income Members across the Centre received the following grants since July 2022 (along with a few earlier grants that were not included in the 2022 Annual Report). Wal-yan Centre researchers and their global collaborators were awarded a total of $17,604,309 in grant funding, covering projects to be delivered between 2021-2027. A breakdown of the awarded grants is presented in the table below. Chief Investigator Prof Stephen Stick

Project Title Priority Driven Childhood Respiratory Research

A/Prof Arresting and reversing Shannon Simpson lung function decline for survivors of preterm birth

Primary Fund Scheme

Start Date

End Date

Total

NHMRC investigator grant

2022

2027

$1,947,721

WA Near-miss Awards

31/12/2021

30/01/2023

$100,000

30/07/2023

$117,865

A/Prof Deb Strickland

Using OM-85 as an innate immune training agent to prevent respiratory infections

OM Pharma Contract Research

31/12/2021

Dr David Martino

Effects of chlorinated drinking water on the assembly of the infant gut microbiome Project (TUMS)

Water Corporation

29/03/2022

30/12/2023

$25,000

Dr Lea-Ann Kirkham

A novel otitis media vaccine: optimising manufacture and dosing strategies for human trials.

WA Child Research Fund (formerly TPCHRF)

29/05/2022

29/05/2023

$599,896

A/Prof Anthony Kicic

Compound repurposing into novel therapeutics to treat SARS-COV2 infection.

MRFF Coronavirus Response Initiative - 2021 COVID-19 Treatment Access and Public Health Activities

31/05/2022

A/Prof Shannon Simpson, Dr Andrew Wilson and Prof. Jane Pillow

Lungs for life: Using wearable oximetry and a virtual ward to improve outcomes of infants with bronchopulmonary dysplasia

MRFF Chronic Respiratory Diseases

1/01/2023

A/Prof Shannon Simpson

Arresting and reversing lung disease for the children of WA who were born too soon

Stan Perron People Fellowship

2023

Kids Infections aNd Day care’s Effects on the lungs in those born Early (KINDEE Study)

Research Excellence Awards - WA Child Health Research Fund

1/06/2022

Deeply phenotyping the Effect of Very and Extremely preterm birth on the Lungs of Primary school children - the DEVELOP Study

NHMRC Ideas WA Near-miss Awards

1/07/2022

Assessing the clinical utility of the lung clearance index in children with bronchiectasis

Australian bronchiectasis centre of research excellence

A/Prof Shannon Simpson

Dr Andrew Wilson

Dr1/06/2023 Kathryn Ramsey

Wal-yan Respiratory Research Centre Annual Report 2023 Page 34

1/06/2023

29/05/2024

30/06/2028

2027

31/06/2024

20/06/2023

31/06/2024

$998,520

$1,918,884.78

$571,729.89

$340,000

$100,000

$25,000

Chief Investigator

Project Title

Primary Fund Scheme

Start Date

End Date

Total

Dr Samuel Montgomery

Establishing a pipeline for repurposing antiinflammatory drugs to tackle viral-induced exacerbations in children with cystic fibrosis

Vertex Cystic Fibrosis Research Innovation Award- Mentored

19/06/2022

19/12/2023

$172,856

A/Prof Anthony Kicic

Enabling the establishment of a phage bioreactor facility for human therapeutic application.

DOH WA FHRIF Innovation Fellowships

26/06/2022

26/06/2023

$145,036

Dr Thomas Iosifidis

Towards preventing respiratory deterioration: a new class of mucosal repair therapeutics

DOH WA FHRIF Innovation Fellowships

26/06/2022

26/06/2023

$110,726

A/Prof Anthony Kicic

Making bacteriophage therapy a reality: Implementation of a novel treatment pipeline to treat antimicrobialresistant infections.

FHIRF - Innovation Seed Fund

27/06/2022

26/06/2024

$500,000

Dr David Hancock

The Microbiome in Young Children with Cystic Fibrosis

Perpetual Impact Grant

30/06/2022

29/06/2025

$54,000

A/Prof Shannon Simpson

Excellence Award