Funded Research

The Dorothy Nell Marzol Innovation Grant

RESEARCHER:  Dr Steven Taylor

PROJECT:  Australian-wide surveillance for fungal infection:  a national metagenomic analysis across 19 cystic fibrosis centres

INSTITUTION:  South Australian Health & Medical Research Institute, South Australia

BUDGET:  $80,000 (1 Year)

SUMMARY:  CF lung infections are devastating. They contribute to both everyday breathlessness as well as exacerbations. Over the last few years, several revolutionary changes have been made to how CF is treated. We are already seeing that the main CF lung pathogens are declining because of these therapies. However, previously when we see changes to the microbes that cause lung infections, we see emergence of new ones. This is concerning as there are no treatment plans for these new microbes. My research will investigate the lung “microbiome” of 912 samples from people with CF across Australia. This will include looking at fungi in the lungs, which are often overlooked, but known to become more common following changes to treatment. By looking at samples collected before and after starting new treatments, we can identify key microbes to monitor, giving us the best chance to protect people with CF from new infections.

REPORTS: Final Report

FBM Lung Health Grant 

(sponsored by not-for-profit partner BTC Speciality Health)

RESEARCHER: Naomi Chapman

PROJECT:  Does the MetaNeb®, a new airway clearance device, change measures of lung oxygenation, secretion clearance and other measures of lung function in adults with cystic fibrosis when they are well?

INSTITUTION:  Curtin University, Western Australia

BUDGET:  $5,000 (1 year)

SUMMARY:  Physiotherapy plays an important role in the management of CF by applying airway clearance techniques, which, reduce the amount of thick secretions in the lungs therefore, reducing lung infections and slowing disease progression. Although there are a range of techniques used to clear airway secretions, there is no evidence to support one over others. The MetaNeb® (Hill-Rom) is a device that delivers positive airway pressure and pulsed flow during inspiration and expiration which could assist in secretion clearance. However, there are no published studies investigating its effects on secretion clearance in adults with CF. There is emerging evidence that using functional magnetic resonance imaging (fMRI) can assist in measuring effectiveness of secretion clearance and lung oxygenation, yet this technique has not been widely used in adults with CF. This study will investigate the MetaNeb® and determine if fMRIs are able to measure secretion clearance and lung oxygenation following airway clearance.

REPORTS: Final Report

Abbie Fennessy Memorial Fellowship 

(sponsored by Mediplast)

RESEARCHER:  Tiffany Dwyer

PROJECT:  Investigations into the associations between exercise, physical activity and sedentary behaviour with glycaemic control in adults with cystic fibrosis after initiation of Trikafta

INSTITUTION:  University of Sydney, New South Wales

BUDGET:  $5,000 (1 year)

SUMMARY:  People with CF often have high and low blood glucose levels (BGLs), which can negatively affect health and quality of life. Diabetes and pre‐diabetes are common in adults with CF, with 40‐50% diagnosed with CF‐related diabetes. In people with other types of diabetes, there is a risk of low BGLs after exercise, but overall improved BGLs with regular exercise. Exercise is important for maintaining and improving health in all people with CF, yet we don’t know the impacts of exercise and physical activity on BGLs.

In April 2022, Trikafta was made available on the PBS for more than 85% of Australians with CF 12 years and older. Trikafta significantly improves lung function and quality of life, but can also cause low BGLs in some people.

This study will use gold‐standard measures of BGLs and physical activity to investigate the effects of exercise and physical activity on BGL control in adults with CF who are taking Trikafta. Results will inform safe exercise prescription (to reduce low BGLs after exercise) and provide guidelines on physical activity and sedentary behaviour (to improve BGL control).

REPORTS: Final Report

CFRL Innovation Grant

(sponsored by Cystic Fibrosis Research Limited, Queensland)

RESEARCHER:   Tamara Blake

PROJECT:  Improving detection and assessment of lung disease in young children with CF

INSTITUTION:  University of Queensland, Queensland

BUDGET:  $80,000 (1 year)

SUMMARY:   In Australia, 1/2500 babies are born with cystic fibrosis (CF). Irreversible damage to their lungs often begins very early in life and without any symptoms. A significant limitation to early detection has been the lack of measures suitable for use in infants/toddlers. Currently used techniques are performed under sedation in specialised laboratories which is often a traumatic experience for patients and their families. We propose to assess the appropriateness of a new, innovative technique – oscillometry – that can be performed during quiet sleep and is very sensitive to early changes in the CF lung. Validation of this technique in this population will provide parents and physicians with detailed lung health information much sooner than current methods. Results from this pilot study will also inform future study designs that will aim to better understand the mechanisms of early CF lung disease and how new techniques can be used to monitor disease progression.

REPORTS:  Progress Report

Conquer CF Lung Health Transplant Grant 

(Sponsored by Conquer Cystic Fibrosis, Western Australia)

RESEARCHER:  Dr Herbert Ludewick

PROJECT:  Transforming diagnosis of lung transplant rejection

INSTITUTION:  Heart & Lung Research Institute, Western Australia

BUDGET:  $48,000 (1 year)

SUMMARY:  Lung transplant offers hope to those with end-stage cystic fibrosis, but half of recipients face mortality within 6-7 years, often due to rejection despite immune suppression. Accurate diagnosis of lung rejection episodes and timely treatment can lengthen healthy survival for CF patients receiving lung transplantation. Detecting rejection currently involves invasive lung sampling under general anaesthesia, posing risks for lung collapse and serious bleeding. Damage to the lung during episodes of rejection can release lung specific DNA into the blood. Our project proposes a blood test to diagnose rejection by detecting elevated lung DNA levels. We aim to find a signature specific to DNA from the lung and test for it in the blood. This non-invasive method will eliminate biopsy risks and simplifies monitoring, potentially extending recipients’ healthy survival. By transforming rejection diagnosis, we aim to enhance outcomes for cystic fibrosis patients post-transplant.

REPORTS:  Progress Report & FINAL REPORT

CFWA Post Graduate Top Up Scholarship 

(sponsored by Cystic Fibrosis Western Australia)

RESEARCHER:  Rohan Flint

PROJECT:  Assessing aerosolised bacteriophage to treat antibiotic resistant bacterial infections

INSTITUTION:  Telethon Kids Institute, Western Australia

BUDGET:  $37,500 (3 years)

SUMMARY:  In recent years, bacterial resistance to antibiotics has grown very quickly, and poses a considerable threat to human health. Bacteriophages or phages are viruses that specifically infect and destroy bacteria, and they have been presented as an alternative therapy for bacterial infections that have become resistant to a large number of antibiotics. Nebulisers can convert a liquid solution into an aerosol and have been proposed as the preferred method to deliver phage to infections within the lung. With little work conducted in this area, this project will use nebulisation to see if phage that can infect antibiotic resistant bacteria can be delivered to treat airway infections. This will be done by first identifying phage that can be nebulised without losing their activity, and then testing their activity against antibiotic-resistant bacteria on infected human airway cells.

REPORTS:  Year 1, Year 2

ACFRT Top Up Scholarship

Project Title: The impact of helpful and harmful immune responses in the CF lung

Principal Researcher: Emma Ledger

Institution: University of Queensland Diamantina Institute

Value:  $15,000

Duration: 3 years

Summary:  Pseudomonas aeruginosa is a highly multi-drug resistant bacteria which causes chronic lung infections in individuals with cystic fibrosis (CF). This bacterium is extremely difficult to eradicate and is a major cause of morbidity and mortality in CF. Our research investigates specific antibodies produced by patients that enhance, rather than clear these bacterial infections resulting in further disease burden.  This project aims to better understand the prevalence, impact, and mechanisms of these ‘bad antibodies’ in individuals with CF by characterising them for the first time within patient sputum and towards the patient’s infecting strain. Additionally, we aim to investigate the impact the latest CF transmembrane conductance regulator (CFTR) modulator therapies have on P. aeruginosa infection and these dysregulated antibody responses. This research is critical for the development of targeted therapies to neutralise these ‘bad antibodies’, clear persistent multi-drug resistant lung infections and improve patient outcomes further in this post-modulator era.

Reports: INTERIM REPORT

CFWA Golf Classic Grant (funded by Cystic Fibrosis Western Australia)

Project Title: Neutrophils in CF

Principal Investigator: Luke Garratt

Institution: Telethon Kids Institute/University of Western Australia

Value:  $28,000

Duration: 1 year

Summary:  In cystic fibrosis (CF), neutrophils accumulate in areas of the lung as mucus builds up and germs infect the airways. My research has found that in CF airway inflammation, neutrophils choose to actively release their harmful products rather than trying to eat and kill the germs causing infection. In a laboratory model of CF airway inflammation, we have found that only certain germs induce this behaviour. We are now studying how the gene expression of neutrophils determines their function, with the aim to understand whether we can prevent certain functions by inducing or repressing genes within the neutrophil. This CFWA funded project is exploring the ability of new nanoparticle technologies to modify gene expression in neutrophils, as neutrophils are short-lived cells that do not respond to traditional methods. The hope is that this technology could inform a new class of anti-inflammatories for controlling neutrophil behaviour in CF airways.

Reports: INTERIM REPORT

The Cystic Fibrosis Metabolic Monitoring Grant (funded by COSMED Asia-Pacific Pty Ltd)

Project Title: The road map to personalised diet management in children with cystic fibrosis

Principal Researchers: Hiran Selvadurai and Andrea Kench

Institution: The Children’s Hospital, Westmead

Value:  $5,000

Duration: 1 year

Summary:  We  know that people with cystic fibrosis (CF) need more energy from food to grow and fight infections than healthy people. However, there is very little information available on specific macronutrient (carbohydrate, protein and fat) requirements for children with CF. In particular, it is not known how macronutrients contribute towards fueling the body during periods of rest and during exercise. This information is needed so that we can implement personalised nutritional goals. This is particularly important in the context of new CF treatments (modulator medications) which have led to a significant improvement in lung function, weight and quality of life. Further, significant infections such as NTM is a growing problem in patients with CF but it is not clear how these infections impact on macronutrient use and energy expenditure in children with CF. Exciting new technologies now enable us to quantify nutritional macronutrient requirements for children. The purpose of this research study is to ascertain if we can determine macronutrient requirements for children with CF. 

Reports: INTERIM REPORT

Ann Maree Bosch Career Fellowship

Project Title: Progressing novel treatment options to improve management of infections in people with cystic fibrosis

Principal Researcher: Stefanie Bader

Institution: Walter & Eliza Hall Institute of Medical Research

Value:  $10,000

Duration: 1 year

Summary: Bacterial infection is the most common cause of death in people with cystic fibrosis (CF). The immune cells responsible for combating bacteria are often defective in CF patients and can damage the lungs and gut while trying to fight infection. This reaction worsens disease and fails to kill the pathogen. We propose to use a new class of drugs that can tackle this problem in two ways: by killing infected host cells, reducing the number of bacteria and by removing defective immune cells. This approach has the potential to improve quality and length of life in people with CF by addressing disease in the lung and the gut.  The Fellowship would provide an invaluable opportunity for me to travel to a lab in the Netherlands which specialises in CF and the gut. There, I would be able to test our drugs both in in-vivo and organoid models of CF gut disease to gain substantial knowledge on how to apply their techniques to our research at WEHI. This would allow my lab to test a greater array of drugs in Australia. I will share the techniques I learn, not just with my lab at WEHI, but with other CF researchers in Australia. 

Reports: FINAL REPORT

Conquer CF (Respiratory) Innovation Grant (funded by Conquer Cystic Fibrosis)

Project Title: Establishing a pipeline for repurposing anti-inflammatory drugs to tackle viral-induced exacerbations in children with cystic fibrois.

Principal Investigator: Samuel Montgomery

Institution: Curtin University/Telethon Kids Institute

Value:  $50,000

Duration: 1 year

Summary:  This study aims to improve the lung health of young children with cystic fibrosis (CF) following a viral infection. Rhinovirus infection (the “cold” virus) is common in young children, often resulting in presentation to hospital emergency departments. This is worsened in children with chronic airway disease such as the inheritable disease cystic fibrosis (CF) where infection with rhinovirus results in deteriorating lung health, sadly often permanently, leading to chronic bacterial infection and increased hospitalisation. Rhinovirus infects the cells lining the airway (the “epithelium”) provoking a large inflammatory response, which can lead to lung damage. We have previously identified a specific type of inflammation which is associated with decreasing lung health in children without bacterial infection. We propose to block this inflammation using a drug, interleukin-1 receptor antagonist, as a new anti-inflammatory treatment for the cold virus in children with CF. We will use a model of the airway in the laboratory to test the safety and effectiveness of this drug to reduce this inflammation. This study aims to provide evidence to progress to a clinical trial, as this drug is already approved for use in other diseases and could be rapidly translated into clinical use for children with CF. 

Reports: INTERIM REPORT & FINAL REPORT

CFWA Golf Committee Contribution to CF Research (funded by Cystic Fibrosis Western Australia)

Project Title: Does a diagnosis of Tracheobronchomalacia affect health outcomes in children with cystic fibrosis?

Principal Researchers: Julie Depiazzi and Crystal Bourke

Institution: Perth Children’s Hospital

Value:  $5,000

Duration: 1 year

Summary:  Around 41% of young children with cystic fibrosis (CF) in Western Australia have been reported to have tracheobronchomalacia (TBM) seen during bronchoscopy – a condition where parts of the windpipe or airways are floppier than would be considered normal. In the short-term this TBM finding can lead to a change of the child’s daily physiotherapy and airway clearance program, however despite its prevalence, little is known about the long-term impact of TBM. 

The aim of this study is to compare health outcomes of children with CF, both with and without TBM, up to the age of 4 years, and will include imaging, inflammation markers and infection comparisons. We hope our findings will provide clinicians and families with more insight into, if any, long-term impacts of this condition.

Reports: INTERIM REPORT & FINAL REPORT

Conquer CF (GI) Innovation Grant (funded by Conquer Cystic Fibrosis)

Project Title: Short Chain Fatty Acids and Gastrointestinal complications in cystic fibrosis

Principal Investigator: Josie van Dorst

Institution: University of New South Wales

Value:  $50,000

Duration: 1 year

Summary: Cystic fibrosis (CF) is a life-shortening genetic condition, which causes thick mucus, chronic infection, and inflammation not only in the lungs but also the gut. People with CF also have an imbalance between beneficial and harmful gut bacteria, which are linked to poor growth, gut symptoms, chronic gut inflammation and increased cancer risk. Short chain fatty acids (SCFA) are produced by beneficial bacteria in the gut, mainly from prebiotic dietary fibres. SCFAs fuel the activities of beneficial bacteria and have many important roles in the gut and wider health, including combating inflammation and cancer activity, and regulating the communication with the lungs (gut-lung axis) and the immune system. Despite this, there is limited knowledge regarding SCFA in individuals with CF.

Reports: NONE DUE

Abbie Fennessy Memorial Fellowship (funded by Mediplast)

Project Title: The Early Childhood Project: Circle of Security-Parenting in cystic fibrosis (CF)

Principal Researcher: Stella Li

Institution: The Children’s Hospital, Westmead

Value: $5,000

Duration: 1 year

Summary:  This project focuses on supporting parents of children with CF during the early childhood period (under 5). This is a period that often coincides with CF diagnosis and can be filled with stress, worry, and guilt. We are offering the Circle of Security parenting program which aims to help parents reflect on and meet their child’s medical and emotional needs and ultimately strengthening the parent-child relationship.

Reports: NONE DUE

CFWA Top Up Scholarship (funded by Cystic Fibrosis Western Australia)

Project Title: Studying how pseudomonias aeruginosa becomes resistant to phage therapy to identify how to prevent it occuring

Principal Researcher: Andrew Vaitekenas

Institution: Curtin University

Value:  $37,500

Duration: 3 years

Summary:   Psuedomonas aeruginosa causes harmful lung infections in CF lungs and becomes resistant to existing antibiotic treatments. There is a lack of antibiotics being developed and alternative treatments are needed. A therapy using viruses that specifically kill bacteria is effective, but P. aeruginosa can become resistant to this too. My project aims to understand how P. aeruginosa becomes resistant to phages and what this means for the bacteria. I will use this knowledge to develop and test strategies that increase the effectiveness of phage therapy and prevent resistance occurring. These strategies can aid our group in making phage therapy a regularly used therapy, preventing further resistance and treating those with infections that are currently untreatable.

Reports: INTERIM REPORT & FINAL REPORT

Special CF Research Seeding Grant (funded by Cystic Fibrosis ACT)

Project Title: Development of new mucus-thinning drugs for CF patients

Principal Researcher: Shiyi Xi

Institution: The Walter & Eliza Hall Institute of Medical Research

Value:  $5,000

Duration: 1 year

Summary:   Mucus-based airway obstructions and the complications they cause are a significant source of morbidity and mortality in CF patients. The current leading mucolytic drug Pulmozyme® only works on 70% of patients, and many people would greatly benefit from more effective alternatives. This project will focus on a promising new target for novel mucolytic drugs – a mucus-thickening protein called trefoil factor-3 (TFF3). My lab has generated and identified 15 candidate antibodies that antagonize TFF3 activity and will be evaluated on patient sputum samples. We aim to benchmark the activity of these potential mucolytics against Pulmozyme® and to assess if they have additive of synergistic activities with the current drugs.

Reports: FINAL REPORT

CFRL Top Up Scholarship  (funded by Cystic Fibrosis Research Limited, Queensland)

Project Title: Investigation of factors influencing glucose control in cystic fibrosis 

Principal Researcher: Rebecca Keating

Institution: University of Queensland

Value:  $15,000

Duration: 3 years

Summary:   This research project will aim to determine whether the use of DPP4 inhibitors assist in removing blood glucose levels for the entire day in individuals with CF impaired glucose tolerance. It will assess its effects on gut hormoneas, gut microbacteria and inflammation. It will also determine whether using a mixed meal tolerance test may be more useful in determining CF impaired glucose tolerance.

Reports: INTERIM REPORT & PROGRESS REPORT

Lung Health Grant (funded by For Benefits Medicine)

Project Title: Telehealth to promote mucociliary clearance in adolescents with cystic fibrosis

Principal Researcher: Anna Middleton

Institution: The Children’s Hospital, Westmead NSW

Value:  $5,000

Duration: 1 year

Summary:   CF adolescents with poor adherence to airway-clearance and exercise will be randomised to a 4-week block of either stationary airway-clearance or the same routine interspersed with short intervals of exercise. Sessions will be supervised by a physiotherapist over telehealth twice a week. After a 2-week wash-out period participants will cross-over to the alternative intervention. Adherence, ease of expectoration, spirometry and exercise perceptions will be measured after each block of therapy. We hope to evaluate whether telehealth in CF adolescents improves airway-clearance technique and adherence and whether the addition of short intervals of exercise interspersed during airway-clearance improves mucociliary-clearance.

Reports: NONE DUE

Innovation Grant  

Project Title: Safety and effectiveness of triple-caftor combinations in cystic fibrosis during pregnancy

Name: Elena Schneider-Futschik

Institution: University of Melbourne

Value:  $80,000

Duration: 1 year

Summary:   The recent approval of the novel CFTR modulator triple combination Trikafta targets the majority of cystic fibrosis (CF) patients, but potentially excludes pregnant women as the clinical efficacy of these important drugs is limited by our lack of understanding what short and long-term effects these drugs could have on developing babies. This project will investigate the entry of the triple combination across the placenta in an animal CF model that replicates a common CF mutation. The project will also assess the potential of maternal administration of these drugs to reduce the amount of CF damage occurring before birth. This innovative approach has significant potential in improving clinical practice worldwide.

Reports: PROGRESS REPORT

CFSA Innovation Grant  (funded by Cystic Fibrosis South Australia)

Project Title: Sphingosine-1 phosphate and zinc – novel mediators of vascular dysfunction in children with CF

Principal Investigator: Andrew Tai

Institution: The University of Adelaide

Value:  $50,000

Duration: 1 year

Summary:  Increased lung artery blood pressure in cystic fibrosis (CF) is linked to poorer survival. Treatment is ineffective as diagnosis usually occurs in adulthood, when the disease is at a later stage. Current CF paradigms are based on the assumption that there is no or minimal lung disease in newborns with CF, and prevention therapy in early childhood has not therefore been considered. We propose a substantial shift in this current paradigm: that there is progression of vascular dysfunction in parallel with the gradual progression of lung disease through childhood in CF and that prevention/intervention therapies before measurable disease would provide a new therapeutic approach. Based on findings by us and others of a role for arterial zinc and sphingosine-1 phosphate (S1P) in cardiovascular disease and a link between zinc and S1P in the vasculature we will investigate blood/ airway samples from children (and adults as controls) with CF, and lungs from CF rats. Long-term treatment with macrolide antibiotic is being increasingly used in CF; however, they this is now known to result in the emergence of antibiotic resistant bacterial strains. We will test a novel non-antibiotic macrolide to address the global priority of halting the generation of further antibiotic resistant bacteria, a profound problem that is one of the biggest threats to global health today.

Reports: INTERIM REPORT & FINAL REPORT

Conquer CF (Respiratory) Innovation Grant (funded by Conquer Cystic Fibrosis)

Project Title: Designing optimal phage cocktails for kids with cystic fibrosis (DOCK-CF)

Principal Investigator: Ameneh Khatami

Institution: University of Sydney

Value:  $50,000

Duration: 1 year

Summary:   To manage chest infections, children with cystic fibrosis (CF) are exposed to broad-spectrum, toxic antibiotics several times per year. This is only moderately effective, with infections often becoming increasingly difficult to treat due to evolving antimicrobial resistance. Bacteriophages (phages) are viruses that replicate within bacteria, causing highly selective bacterial killing. Since phages do not attack human cells they are safe for clinical use, and their targeted bacterial killing reduces their impact on our healthy microbiome (commensal bacteria). Thus, phage therapy offers a safer and more precise solution than antibiotics.We hypothesise that Pseudomonas aeruginosa and Staphylococcus aureus strains that colonise children with CF can be eradicated effectively by combinations of phages (“phage cocktails”). This would result in reduced lung damage and allow recovery of normal lung growth, improving the life expectancy of children with CF. In addition, reduced toxicity and microbiome effects compared to antibiotics would improve quality of life for patients and their families. This proposal aims to identify phages with ‘killing’ activity against the main strains of these bacteria isolated from a large cohort of children with CF.  Research outcomes will feed into a translational pipeline to investigate this promising therapy in children with CF within 5 years.

Reports: INTERIM & FINAL REPORT

Golf PhD Top Up Scholarship (funded by Cystic Fibrosis Western Australia)

Project Title: Me, myself and I: An exploratory study of self-concept in adults with Cystic Fibrosis (CF) in an evolving era of care.

Principal Researcher: Maggie Harrigan

Institution: University of Western Australia

Value:  $37,500

Duration: 3  years

Summary:   The PhD study explores self-concept (sometimes called self-identity) e.g. how you view yourself, a sense of who you are as a person in the various aspects of life. Outside CF, self-concept has been widely associated with improved health, however there is currently a lack of self-concept research within CF. I will be examining levels of self-concept within the adult CF community and associations between self-concept, mental, social and physical health. The study will also explore the potential impact of evolving CFTR modulator treatments on self-concept.  As CF treatments evolve, what is means to have CF continues to change, potentially bringing new opportunities and challenges.  Amidst this change it is pertinent to develop our understanding of the social and emotional needs of those living with CF.  

Publication: ‘Me, myself, and I: A systematic review of cystic fibrosis and self‐concept’.

Report: INTERIM

Golf PhD Top Up Scholarship (funded by Cystic Fibrosis Western Australia)

Project Title: Investigating an alternative therapeutic agent for the treatment for bacterial infections in kids with cystic fibrosis

Principal Researcher: Joshua Iszatt

Institution: Curtin University

Value:  $37,500

Duration: 3  years

Summary:   This project is focused around the development and investigation of a therapeutic agent that could be used to treat multi-drug resistant bacteria tha frequently cause persistent lung infections in children with cystic fibrosis.

Report: INTERIM & FINAL REPORT

Ann Maree Bosch Fellowship

Project Title: The Gut-Lung Axis in early cystic fibrosis (GLAX-CF)

Principal Researcher: Katherine Frayman

Institution: Murdoch Children’s Research Institute

Value:  $9,500

Duration: 1 year

Summary:  My research explores the development of the gastrointestinal and lower airway microbiota during the first two years of life in newly diagnosed infants with cystic fibrosis, and their relationship to each other, to lower airway inflammation and to clinical manifestations of disease. It will examine the impact of continuous antibiotic prophylaxis on the microbial milieu in both niches, and its relationship to clinically relevant outcomes. Ultimately, my research aims to highlight opportunities for intervention, for example, modification of the gastrointestinal microbiota with pro-, pre- or antibiotics, in order to influence respiratory phenotype. The Ann Maree Bosch Career Fellowship will enable me to travel to the United States to establish key collaborations with the University of Washington and Seattle Children’s Hospital, Washington and attend the North American Cystic Fibrosis Conference.

Report: NONE DUE

Conquer CF (GI) Innovation Grant (funded by Conquer Cystic Fibrosis)

Project Title: Towards understanding gut host-microbe interactions and personalised probiotic therapy in cystic fibrosis using organoid-derived 2D intestinal models

Principal Investigator: Keith Ooi

Institution: University of New South Wales

Value:  $50,000

Duration: 1 year

Summary: Cystic fibrosis (CF) is a life-shortening genetic condition, which causes thick mucus, chronic infection, and inflammation in the lungs and gastrointestinal (GI) tract. People with CF have an imbalance in their GI bacterial population (microbiome) known as “dysbiosis”, and chronic GI inflammation, both of which are linked to poor growth, GI symptoms and increased cancer risk. A survey of CF patients and clinicians globally has ranked GI symptoms 2nd in priority, ahead of respiratory issues, yet no GI-specific therapies currently exist. Stem cells obtained from gut biopsies from people with CF can be used to grow 2-dimensional and 3-dimensional organoid culture systems which replicate real life (“mini guts”). We will investigate the host-microbe interactions involved in GI dysbiosis, inflammation and malignancy, using CF patient-specific intestinal organoids. We believe this study will provide a crucial step towards personalised therapies based on host-microbe interactions with the aim of reducing GI complications in CF. Successful personalised therapies would revolutionise CF treatments and other conditions subject to host-microbe interactions. 

Reports: NONE DUE

Abbie Fennessy Memorial Fellowship (funded by Technipro-Pulmomed Pty Ltd)

Project Title: CF Physio.com:  development of interactive and education videos of inhalation therapy and airway clearance

Principal Researchers: Jen Hauser & Jenny Bishop

Institution: Royal Hobart Hospital & Westmead Hospital

Value: $5,000

Duration: 1 year

Summary:  CFPhysio.com is an educational website which currently translates the TSANZ clinical practice guidelines “Physiotherapy for CF”, and evidence based educational literature into a practical, self-paced, educational resource for physiotherapists. The website currently provides a platform for education and learning of evidence-based physiotherapy management in cystic fibrosis, for physiotherapists. Since its official launch in August 2019, over 400 physiotherapists have registered and used the site. A second stage of the project is proposed, including the provision of educational resources for individuals with CF, carers, family, friends, employers, teachers etc, including video content of inhalation therapy and physiotherapy treatment techniques. 

Report: FINAL REPORT

Innovation Grant

Project Title: Enhancing the innate ability of CF macrophages to kill and clear MABS

Principal Investigator: Abdullah Tarique

Institution: University of Queensland

Value: $80,000

Duration: 1 Year

Summary: Currently 13-20% of patients with CF are infected with Mycobacterium abscessus (MABS) and there is growing concern that increasing incidence of MABS infection is leading to accelerated pulmonary decline, and to reduced survival. MABS are notoriously difficult to treat, in part because of widespread antibiotic resistance, thus necessitating the use of toxic drug regimens. We herein propose to evaluate an alternative approach to clear MABS by boosting the anti-bacterial responses of CF patients using novel therapeutic agents. Macrophages are the professional killer cells that kill bacteria including MABS from the lungs. Sputum and venous blood are the two main sources for macrophage researchers. Due to inadequate volume of patient’s specimen available for research, macrophage researchers struggle in getting enough macrophages from patients’ specimen which thereby limit macrophage research in CF. We herein propose to develop an immortalized CF macrophage cell line that will offer indefinite supply of CF macrophages to the researchers to investigate macrophage defect in CF as well as finding out ways to improve their anti-microbial responses in CF.

Report:  FINAL REPORT

Ann Maree Bosch Career Fellowship

Project Title: Targeting a forgotten cell to prevent cystic fibrosis lung disease

Principal Researcher: Shivanthan Shanthikumar

Institution: Murdoch Children’s Research Institute

Value: $9,000

Duration: 1 year

Summary:  The life expectancy for someone born with cystic fibrosis (CF) today is only 44 years. In CF the major cause of shortened life expectancy, as well as reduced quality of life, is lung disease. A major cause of lung disease in CF is excessive inflammation which causes to irreversible lung damage. Currently a number of treatments are used in CF such as antibiotics and chest physiotherapy, however no treatments target inflammation. There are new treatments which address the malfunctioning ion channel which causes CF, however these treatments only target specific certain genetic mutations, and so not all patients benefit from them. Any treatments aimed at inflammation in CF would benefit all patients, and could be used together with existing and new treatments. There are a number of different cell types that contribute to inflammation, however one that has not been investigated is the alveolar macrophage. These cells only exist in the lung and are one of the initial cells that trigger an inflammatory response. There are multiple types of alveolar macrophages in CF lungs, and thus far they have not been studied. The overall aim of my research is to identify targets for treatment relating to alveolar macrophages.

Report: FINAL REPORT

David Millar Giles Innovation Grant

Project Title:  An Australian Alliance of personalised lab grown mini-organs to save the rarest of them all

Principal Investigator: Shafagh Waters

Institution: University of New South Wales

Value: $45,000

Duration: 1 Year

Summary: Some individuals with rare CFTR mutations have been shown to benefit from the available modulator therapies. Sadly, most will have no opportunity to access these breakthrough treatments. Currently no clinical test exists to predict patient’s response to a modulator drug. We are using a new technology in the field of personalised medicine. Stem cell derived mini-organs are generated from small biopsies serving as a personal CF model or an AVATAR. They are tested in the lab to predict an individual CF patients’ responses to therapeutic agents. Should one or more therapies prove effective in the lab, these can be recommended for use as targeted therapies for the patient.

In the last 2 years we have created AVATARs from children with CF that visit the Sydney Children’s Hospital and have predicted outcome of modulator therapies. In this application we propose to extend our platform to create an Australian-wide alliance for people with rare CF by extending to 11 CF clinics (6 paediatric and 5 adult). This project will provide a novel therapeutic opportunity, ultimately enabling ‘managed’ off-label access to the CFTR modulator therapies for individuals with rare CFTR mutations who show response to the therapy in a prospective mini-organ test.

Reports: FINAL REPORT

Innovation Grant 

Project Title: Optimising patient-derived stem cell technology in cystic fibrosis to predict CFTR modulator response

Principal Investigator: Gerard Kaiko

Institution: University of Newcastle and Hunter Medical Research Institute (Newcastle and Northern NSW)

Value: $80,000

Duration: 1 Year

Summary: CFTR modulator therapy offers great hope to improve the quality of life of cystic fibrosis (CF) patients with an array of different mutations. However, the high-cost, limitations of efficacy, and restrictions of therapies to clinical trial targeted mutations has created a powerful need for a lab test to better predict which CFTR mutations and which individual patients will respond to a given therapy. This type of precision-medicine is already critical but will only become more vital in the future as CFTR modulator therapy options increase. Stem cell technology has enabled patient cells to be readily grown in the laboratory. The use of ‘mini-guts’, grown from a CF patient intestinal biopsy, is being used in the Netherlands to suggest whether a given CFTR mutation may respond to a given therapy. To enable this type of testing to be put into practice in Australia there are two major questions that we aim to address in this project. Firstly, what is the optimal stem cell technology and functional test to apply to patient cells to determine whether they will respond to therapy. Secondly, can we predict a patient’s response to CFTR therapy in the clinic by testing the drugs on their stem cells.

Reports: 6 MONTH & FINAL REPORT

Innovation Grant (funded by Cystic Fibrosis Community Care Victoria)

Project Title: Colorectal Cancer

Principal Investigator: Keith Ooi

Institution: University of New South Wales

Value: $50,000

Duration: 1 Year

Summary: Adults with cystic fibrosis (CF) now face new complications such as colorectal cancer (CRC). The cause is unknown but gut inflammation and gut bacteria imbalances are possible causes. The risk for CRC in CF is high enough that new CRC screening guidelines recommend colonoscopy for patients >40 years and for post-transplant patients >30 years old. Performing colonoscopies in adult CF patients is complex due to comorbid diseases including poor lung function and diabetes. Non-invasive screening tests are needed, similar to faecal occult blood testing (FOBT) used for general population screening. While FOBT utility in CF remains unclear, other stool tests for gut inflammation (calprotectin and M2-PK) have shown promise in detection of CRC and polyps in the general population. They are elevated in children with CF and may be potential early markers of future CRC in adults with CF. To investigate this further, we will invite patients who meet criteria for CRC screening to provide stool samples prior to their scheduled colonoscopies. Markers of gut inflammation including calprotectin and M2-PK, FOBT and imbalances in gut bacteria will be assessed and compared with incidence of CRC and number of adenomas. Predictors for colorectal cancer and precancerous lesions will also be assessed.

Reports: INTERIM REPORT & UPDATE REPORT & FINAL REPORT

ACFRT Top-up Scholarship

Project Title: Adverse Early Risk Factors for Adult Cardiovascular Disease in Paediatric Cystic Fibrosis

Principal Researcher: Thomas Saunders

Institution: Murdoch Children’s Research Institute

Duration: 3 years

Value: $15,000

Summary: Life with cystic fibrosis (CF) has undergone dramatic changes over the past decades, thanks to early interventions throughout childhood, including a high fat diet. Unlike previous generations, current CF children are living beyond their twenties, and now into their fifth or sixth decades. However the new medical challenges they will face are largely unknown. In particular, the impact of the leading causes of death worldwide, atherosclerosis and cardiovascular disease (CVD- heart attack and stroke), are unknown. Lung diseases similar to CF have much higher risks of CVD than the general population and there are increasing case reports of CF individuals developing CVD.

Atherosclerosis (hardening of the arteries) is thought to be largely preventable, especially when intervention starts in childhood. Risk factors such as inflammation, metabolic stress, and abnormal fat metabolism are all found in people with CF; but they are also prescribed high-fat diets, necessary to maintain good weight gain and growth. As CF life expectancy improves, and there are more and more instances of CVD in CF adults, novel studies aiming to detect it will be crucial.

This study investigates if CF children have early changes to blood vessels, biomarkers and immune system that may lead to atherosclerosis and CVD in adulthood. We will perform non-invasive ultrasounds looking at arteries, assess smaller vessels with retinal photographs, and measure specific biomarkers and immune cells in the blood.

This study is expected to show that CF children do have changes that suggest they may be at higher risk of atherosclerosis and CVD in the future. This will indicate if our current nutritional goals are sufficient, and guide changes to minimise the impact of CVD in CF adults. As people with CF live longer, it is critical that their increased survival also has improved quality of life with any treatment side-effects minimised. As such, this study will have a direct impact on how we treat people with CF in the future.

Reports: NONE DUE

ACFRT Top-up Scholarship

Project Title: Computer Modelling of the Root Cause of Cystic Fibrosis

Principal Researcher: Miro Astore

Institution: The University of Sydney

Duration: 3 years

Value: $5,000

Summary: We will use physics based atomic models to develop our understanding of cystic fibrosis and find treatments for it. With a focus on those who cannot currently access existing treatments.

Reports: FINAL REPORT

CFWA Golf Classic Scholarship (funded by Cystic Fibrosis Western Australia)

Project Title: Exploring the therapeutic potential of phage therapy to treat Pseudomonas aeruginosa infection in people with cystic fibrosis

Principal Researcher: Renee Ng

Institution: University of Western Australia

Value: $37,500

Duration: 3 years

Summary: This study aims to explore a new treatment option for patients with bacterial lung infections using bacteriophages (‘phages’), a virus that targets and “eats” bacteria, eradicating them. Phage therapy is cheaper causes no side effects which is seen with currently used antibiotics. This project aims to understand if phage therapy can kill the bacteria and reduce the inflammation caused by infection.

Report:  FINAL REPORT

CFWA Golf Classic Scholarship (funded by Cystic Fibrosis Western Australia)

Project Title:  Does the MetaNeb®, a new airway clearance device, change lung function in adults with cystic fibrosis when they are well and when they are hospitalised for a lung infection?

Principal Researcher: Naomi Chapman

Institution: Curtin University

Value:  $37,500

Duration: 3 years

Summary:  Cystic fibrosis (CF) is an inherited lung disease that causes excessive airway secretions, damaging airways and leading to chronic infection. Clearing the airways is a vital component of their care and is believed to reduce lung infections and slow disease progression. Although there are a range of techniques used to clear airway secretions, there is no evidence to support one over others. Therefore, the choice of technique is based largely on patient/therapist preference. This project will look at the effects of a new airway clearance device called the MetaNeb®, on lung function, secretion clearance and CF related symptoms in adults with CF who are well and those hospitalised with a respiratory exacerbation or chest infection. If this device is shown to be more effective than the commonly used techniques, this would be of great clinical significance as it will assist in guiding clinical use of the device throughout CF centres in Australia and internationally.

Report: FINAL REPORT

Abbie Fennessy Memorial Fellowship (funded by Technipro-Pulmomed Pty Ltd)

Project Title: Infection Control and prevention with non-invasive ventilation use

Principal Researcher: Olivia McGuiness

Institution: Royal Prince Alfred Hospital

Value: $5,000

Duration: 1 year

Summary: Infection control and prevention is of paramount importance in the health care setting. The National Health and Medical Research Council in collaboration with the Australian Commission on Safety and Quality in Healthcare emphasize the importance of standard and transmission-based precautions (NHMRC, 2010). Recommendations for infection control and prevention are outlined for several commonly used medical devices including central venous catheters and mechanical ventilators used in the intensive care. There are no such guidelines for non-invasive ventilator (NIV) devices. Due to its high costs, patients usually obtain these devices from a hospital or government equipment loan program. NIV devices are used or the management of patients with acute and chronic respiratory failure including those with chronic obstructive lung disease (COPD), sleep disordered breathing and suppurative lung diseases, like Cystic Fibrosis (CF).

Report: NONE DUE