Director, Wal-yan Respiratory Research Centre
MB BChir PhD MRCP FRACP
Areas for research expertise: Research Interests; Paediatric respiratory disease; Cystic fibrosis; Respiratory epithelium; Lung structure-function relation; Health service delivery models
Dr Stick is a career clinician and clinical researcher and holds a National Health and Medical Research (NHMRC) Practitioner Fellowship. Dr Stick is a member of the Royal Australasian College of Physicians Research and Education Subcommittee, the NHMRC Scholarships Committee and the NHMRC Grant Review Panel. He is also a member of the American Thoracic Society (ATS), Pediatric Program Committee, Joint ATS/European Respiratory Society (ERS) Task Force on Infant Lung Function and USCF Foundation Data Safety Monitoring Committee.
In 2007, Dr Stick was appointed Clinical Lead of the Health Department of Western Australia, Respiratory Health Network, responsible for the translation of evidenced based models of care into state-wide health policy. Since 2005, he has been the Principal Investigator for the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). AREST CF has developed a unique early surveillance program that has focussed attention on early manifestations of CF lung disease and has contributed to a paradigm shift from an approach based on amelioration of respiratory disease to one focussed on prevention of bronchiectasis, the major cause of morbidity/mortality in CF.
In July 2010, a collaboration between centres in Perth and Melbourne to investigate early childhood lung disease that Dr Stick lead was designated as a NHMRC Centre of Research Excellence. Dr Stick is also principal investigator for the 1st intervention trial to prevent bronchiectasis in newborns diagnosed with cystic fibrosis (COMBAT CF).
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Projects
Lung damage in children with CF occurs much earlier than previously thought, and proving this is related to the decline that occurs later will create new paradigms for prevention and treatment.
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Publications
December 2022
Genome Sequences of Two Lytic Staphylococcus aureus Bacteriophages Isolated from Wastewater
Two lytic double-stranded DNA (dsDNA) bacteriophages, belonging to the family Herelleviridae, were isolated from wastewater in Western Australia. Biyabeda-mokiny 2 appears to belong to the genus Kayvirus, and Koomba-kaat 1 to Silviavirus.
Published research Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental Health Subsite: WalyanDecember 2022Genome Sequence of a Lytic Staphylococcus aureus Bacteriophage Isolated from Breast Milk
We identified a double-stranded DNA (dsDNA) bacteriophage appearing to belong to Herelleviridae, genus Kayvirus. The bacteriophage, Biyabeda-mokiny 1, was isolated from breast milk using a clinical isolate of Staphylococcus aureus.
Published research Inflammation Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental Health Subsite: WalyanDecember 2022Standardised 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
There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy.
Published research Infectious Diseases Epidemiology P4 Respiratory Health for Kids Subsite: WalyanDecember 2022Bacteriophage: A new therapeutic player to combat neutrophilic inflammation in chronic airway diseases
Persistent respiratory bacterial infections are a clinical burden in several chronic inflammatory airway diseases and are often associated with neutrophil infiltration into the lungs. Following recruitment, dysregulated neutrophil effector functions such as increased granule release and formation of neutrophil extracellular traps (NETs) result in damage to airway tissue, contributing to the progression of lung disease.
Published research Infectious Diseases Airway Epithelial Research P4 Respiratory Health for Kids Subsite: WalyanDecember 2022Complete Genomes of Three Pseudomonas aeruginosa Bacteriophages, Kara-mokiny 1, Kara-mokiny 2, and Kara-mokiny 3
Here, we present the complete genome sequence of Pseudomonas aeruginosa phages Kara-mokiny 1, Kara-mokiny 2, and Kara-mokiny 3. These phages have lytic capabilities against P. aeruginosa and belong to the myovirus morphotype. The genomes of Kara-mokiny 1 and Kara-mokiny 2 are 67,075 bp while that of Kara-mokiny 3 is 66,019 bp long.
Published research Airway Epithelial Research P4 Respiratory Health for Kids Subsite: WalyanDecember 2022Complete Genome Sequences of Four Pseudomonas aeruginosa Bacteriophages: Kara-mokiny 8, Kara-mokiny 13, Kara-mokiny 16, and Boorn-mokiny 1
Pseudomonas aeruginosa is an opportunistic pathogen. Here, we report the isolation of four bacteriophages from wastewater. All four bacteriophages belong to the Myoviridae family.
Published research Airway Epithelial Research P4 Respiratory Health for Kids Subsite: WalyanMarch 2022The 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
In the Saline Hypertonic in Preschoolers (SHIP) study, inhaled 7% hypertonic saline improved the lung clearance index in children aged 3-6 years with cystic fibrosis, but it remained unclear whether improvement is also seen in structural lung disease. We aimed to assess the effect of inhaled hypertonic saline on chest CT imaging in children aged 3-6 years with cystic fibrosis.
Cystic Fibrosis Published research P4 Respiratory Health for Kids Subsite: WalyanMarch 2022Investigating the Implications of CFTR Exon Skipping Using a Cftr Exon 9 Deleted Mouse Model
Severity and disease progression in people with Cystic Fibrosis is typically dependent on their genotype. One potential therapeutic strategy for people with specific mutations is exon skipping with antisense oligonucleotides. CFTR exon 9 is an in-frame exon and hence the exclusion of this exon would excise only 31 amino acids but not alter the reading frame of the remaining mRNA.
Cystic Fibrosis Published research Airway Epithelial Research Subsite: WalyanFebruary 2022Comparison 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
To compare type 2 polysomnography (T2PSG) to the gold standard type 1 in-laboratory polysomnography (T1PSG) for diagnosing obstructive sleep apnea (OSA) in children; validate home T2PSG in children with suspected OSA.
Published research Child Disability Subsite: WalyanFebruary 2022Primary Nasal Epithelial Cells as a Surrogate Cell Culture Model for Type-II Alveolar Cells to Study ABCA-3 Deficiency
ATP Binding Cassette Subfamily A Member 3 (ABCA-3) is a lipid transporter protein highly expressed in type-II alveolar (AT-II) cells. Mutations in ABCA3 can result in severe respiratory disease in infants and children. To study ABCA-3 deficiency in vitro, primary AT-II cells would be the cell culture of choice although sample accessibility is limited. Our aim was to investigate the suitability of primary nasal epithelial cells, as a surrogate culture model for AT-II cells, to study ABCA-3 deficiency.
Published research Airway Epithelial Research Subsite: Walyan BREATH Translational GeneticsJanuary 2022A screening tool to identify risk for bronchiectasis progression in children with cystic fibrosis
The marked heterogeneity in cystic fibrosis (CF) disease complicates the selection of those most likely to benefit from existing or emergent treatments. We aimed to predict the progression of bronchiectasis in preschool children with CF.
Cystic Fibrosis Published research Subsite: WalyanJune 2022Macrophage PD-1 associates with neutrophilia and reduced bacterial killing in early cystic fibrosis airway disease
Macrophages are the major resident immune cells in human airways coordinating responses to infection and injury. In cystic fibrosis, neutrophils are recruited to the airways shortly after birth, and actively exocytose damaging enzymes prior to chronic infection, suggesting a potential defect in macrophage immunomodulatory function.
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for Kids Subsite: WalyanMay 2022Association between early respiratory viral infections and structural lung disease in infants with cystic fibrosis
Infants with cystic fibrosis (CF) develop structural lung disease early in life, and viral infections are associated with progressive lung disease. We hypothesized that the presence of respiratory viruses would be associated with structural lung disease on computed tomography (CT) of the chest in infants with CF.
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for Kids Subsite: WalyanMay 2022AI-Driven Cell Tracking to Enable High-Throughput Drug Screening Targeting Airway Epithelial Repair for Children with Asthma
The airway epithelium of children with asthma is characterized by aberrant repair that may be therapeutically modifiable. The development of epithelial-targeting therapeutics that enhance airway repair could provide a novel treatment avenue for childhood asthma.
Published research Airway Epithelial Research P4 Respiratory Health for Kids Subsite: WalyanMay 2022Pseudomonas aeruginosa modulates neutrophil granule exocytosis in an in vitro model of airway infection
A population of neutrophils recruited into cystic fibrosis (CF) airways is associated with proteolytic lung damage, exhibiting high expression of primary granule exocytosis marker CD63 and reduced phagocytic receptor CD16. Causative factors for this population are unknown, limiting intervention. Here we present a laboratory model to characterize responses of differentiated airway epithelium and neutrophils following respiratory infection.
Cystic Fibrosis Published research Infectious Diseases Airway Epithelial Research P4 Respiratory Health for Kids Subsite: Walyan Respiratory viral infectionsApril 2022Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis
Mucus hyperconcentration in cystic fibrosis (CF) lung disease is marked by increases in both mucin and DNA concentration. Additionally, it has been shown that half of the mucins present in bronchial alveolar lavage fluid from preschool-aged CF patients are present in as non-swellable mucus flakes.
Cystic Fibrosis Published research Subsite: WalyanMarch 2021Role of Tris-CaEDTA as an adjuvant with nebulised tobramycin in cystic fibrosis patients with Pseudomonas aeruginosa lung infections: A randomised controlled trial
We tested if disrupting iron utilisation by P. aeruginosa by adding the Tris-buffered chelating agent CaEDTA to nebulised tobramycin would enhance bacterial clearance and improve lung function in CF patients.
Cystic Fibrosis Published research P4 Respiratory Health for Kids Subsite: WalyanDecember 2021Dysregulated Notch Signaling in the Airway Epithelium of Children with Wheeze
The airway epithelium of children with wheeze is characterized by defective repair that contributes to disease pathobiology. Dysregulation of developmental processes controlled by Notch has been identified in chronic asthma. However, its role in airway epithelial cells of young children with wheeze, particularly during repair, is yet to be determined.
Asthma Published research Airway Epithelial Research P4 Respiratory Health for Kids Bacterial Respiratory Infectious Disease Group Subsite: WalyanFebruary 2021Pseudomonas aeruginosa Resistance to Bacteriophages and Its Prevention by Strategic Therapeutic Cocktail Formulation
Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials.
Cystic Fibrosis Published research Subsite: WalyanJanuary 2021Overcoming Challenges to Make Bacteriophage Therapy Standard Clinical Treatment Practice for Cystic Fibrosis
Individuals with cystic fibrosis (CF) are given antimicrobials as prophylaxis against bacterial lung infection, which contributes to the growing emergence of multidrug resistant (MDR) pathogens isolated. Pathogens such as Pseudomonas aeruginosa that are commonly isolated from individuals with CF are armed with an arsenal of protective and virulence mechanisms, complicating eradication and treatment strategies.
Cystic Fibrosis Published research Airway Epithelial Research Subsite: WalyanJanuary 2021Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis
Neutrophil elastase is a significant risk factor for structural lung disease in cystic fibrosis, and Pseudomonas aeruginosa airway infection is linked with neutrophilic inflammation and substantial respiratory morbidity. We aimed to evaluate how neutrophil elastase (NE) activity changes after P. aeruginosa eradication and influences early disease outcomes. We assessed participants in the AREST CF cohort between 2000 and 2018 who had P. aeruginosa cultured from their routine annual bronchoalveolar lavage (BAL) fluid and who underwent eradication treatment and a post eradication BAL. Factors associated with persistent P. aeruginosa infection, persistent neutrophilic inflammation following eradication and worse structural lung disease one year post-eradication were evaluated.
Cystic Fibrosis Published research Early Childhood Development Airway Epithelial Research Subsite: WalyanJanuary 2021ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma
COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. We obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC.
Asthma Published research Airway Epithelial ResearchNovember 2021Development and validation of a miniaturized bacteriophage host range screening assay against antibiotic resistant Pseudomonas aeruginosa
Antimicrobial resistance is a current global health crisis, and the increasing emergence of multidrug resistant infections has led to the resurgent interest in bacteriophages as an alternative treatment.
Published research Airway Epithelial Research Subsite: WalyanSeptember 2021Phage therapy for multi-drug resistant respiratory tract infections
The emergence of multi-drug resistant (MDR) bacteria is recognised today as one of the greatest challenges to public health. As traditional antimicrobials are becoming ineffective and research into new antibiotics is diminishing, a number of alternative treatments for MDR bacteria have been receiving greater attention. Bacteriophage therapies are being revisited and present a promising opportunity to reduce the burden of bacterial infection in this post-antibiotic era.
Published research Subsite: Walyan Immune systemAugust 2021A cluster randomized trial of interferon ss-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19)
SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19).
Infectious Diseases Subsite: Walyan Systems Vaccinology COVID-19August 2021Previous Influenza Infection Exacerbates Allergen Specific Response and Impairs Airway Barrier Integrity in Pre-Sensitized Mice
In this study we assessed the effects of antigen exposure in mice pre‐sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression.
Published research Influenza Airway Epithelial Research Respiratory Environmental Health Subsite: WalyanAugust 2021Cystic fibrosis clinical isolates of aspergillus fumigatus induce similar muco-inflammatory responses in primary airway epithelial cells
Aspergillus is increasingly associated with lung inflammation and mucus plugging in early cystic fibrosis disease during which conidia burden is low and strains appear to be highly diverse. It is unknown whether clinical Aspergillus strains vary in their capacity to induce epithelial inflammation and mucus production.
Cystic Fibrosis Published research Subsite: WalyanJune 2021Lung inflammation and simulated airway resistance in infants with cystic fibrosis
Cystic fibrosis (CF) is characterized by small airway disease; but central airways may also be affected. We hypothesized that airway resistance estimated from computational fluid dynamic (CFD) methodology in infants with CF was higher than controls and that early airway inflammation in infants with CF is associated with airway resistance.
Cystic Fibrosis Published research Children's Lung Health Subsite: Cystic Fibrosis Subsite: WalyanJune 2021Systems biology and bile acid signalling in microbiome-host interactions in the cystic fibrosis lung
The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review is focused on the genetically inherited condition of Cystic Fibrosis.
Cystic Fibrosis Published research Subsite: Cystic Fibrosis Subsite: WalyanApril 2021Time to get serious about the detection and monitoring of early lung disease in cystic fibrosis
Structural and functional defects within the lungs of children with cystic fibrosis (CF) are detectable soon after birth and progress throughout preschool years often without overt clinical signs or symptoms. By school age, most children have structural changes such as bronchiectasis or gas trapping/hypoperfusion and lung function abnormalities that persist into later life. Despite improved survival, gains in forced expiratory volume in one second (FEV1) achieved across successive birth cohorts during childhood have plateaued, and rates of FEV1 decline in adolescence and adulthood have not slowed. This suggests that interventions aimed at preventing lung disease should be targeted to mild disease and commence in early life.
Cystic Fibrosis Published research Subsite: WalyanDecember 2020BAL Inflammatory Markers Can Predict Pulmonary Exacerbations in Children With Cystic Fibrosis
Pulmonary exacerbations in cystic fibrosis are characterized by airway inflammation and may cause irreversible lung damage. Early identification of such exacerbations may facilitate early initiation of treatment, thereby potentially reducing long-term morbidity. Research question: Is it possible to predict pulmonary exacerbations in children with cystic fibrosis, using inflammatory markers obtained from BAL fluid?
Cystic Fibrosis Published research Early Childhood Development P4 Respiratory Health for Kids Subsite: Cystic Fibrosis Subsite: WalyanDecember 2020Minimal structural lung disease in early life represents significant pathology
In this cohort, as compared with the AREST CF cohort, the authors highlight the limited correlation between infection and inflammation with lung function and structural impairment, and that this was mainly explained by the mild changes identified in lung function and on chest CT scan.
Cystic Fibrosis Published research Subsite: WalyanNovember 2020Bile Acid Signal Molecules Associate Temporally with Respiratory Inflammation and Microbiome Signatures in Clinically Stable Cystic Fibrosis Patients
Cystic fibrosis (CF) is a congenital disorder resulting in a multisystemic impairment in ion homeostasis. The subsequent alteration of electrochemical gradients severely compromises the function of the airway epithelia.
Published researchOctober 2020Microbiomic Analysis on Low Abundant Respiratory Biomass Samples; Improved Recovery of Microbial DNA From Bronchoalveolar Lavage Fluid
In recent years the study of the commensal microbiota is driving a remarkable paradigm shift in our understanding of human physiology. However, intrinsic technical difficulties associated with investigating the Microbiomics of some body niches are hampering the development of new knowledge. This is particularly the case when investigating the functional role played by the human microbiota in modulating the physiology of key organ systems. A major hurdle in investigating specific Microbiome communities is linked to low bacterial density and susceptibility to bias caused by environmental contamination.
Published research P4 Respiratory Health for Kids Subsite: WalyanOctober 2020Early disease surveillance in young children with cystic fibrosis: A qualitative analysis of parent experiences
Sensitive measures of early lung disease are being integrated into therapeutic trials and clinical practice in cystic fibrosis (CF). The impact of early disease surveillance (EDS) using these novel and often intensive techniques on young children and their families is not well researched.
Cystic Fibrosis Published research Child Health, Development & Education P4 Respiratory Health for Kids Children’s Respiratory ScienceJune 2020Azithromycin Partially Mitigates Dysregulated Repair of Lung Allograft Small Airway Epithelium
Chronic airway injury and dysregulated repair programs are evident in airway epithelium obtained from patients with bronchiolitis obliterans syndrome
Published research Airway Epithelial Research P4 Respiratory Health for KidsJune 2020Assessing the unified airway hypothesis in children via transcriptional profiling of the airway epithelium
Upper and lower airways are conserved in their transcriptional composition, and variations associated with disease are present in both nasal and tracheal epithelium
Published research Systems Immunology Computational Biology Airway Epithelial Research P4 Respiratory Health for KidsJune 2020Epithelial Mesenchymal Transition in Respiratory Disease: Fact or Fiction
In this translational review, the mechanisms, roles, and impact of epithelial-mesenchymal transition in chronic lung diseases are discussed
Published research Airway Epithelial Research P4 Respiratory Health for KidsMay 2020Assessment of early lung disease in young children with CF: A comparison between pressure-controlled and free-breathing chest computed tomography
Our data suggest that FRC PC-CTs are less sensitive than TLC PC-CTs and that FB-CTs have similar sensitivity to PC-CTs in detecting lung disease
Cystic Fibrosis Published research P4 Respiratory Health for KidsMay 2020The detection of bile acids in the lungs of paediatric cystic fibrosis patients is associated with altered inflammatory patterns
Our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease
Cystic Fibrosis Published research P4 Respiratory Health for KidsMay 2020Structural determinants of long term functional outcomes in young children with cystic fibrosis
Chest CT identifies children at an early age who have adverse long-term outcomes
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsApril 2020Rhinovirus Infection Is Associated With Airway Epithelial Cell Necrosis and Inflammation via Interleukin-1 in Young Children With Cystic Fibrosis
This study found rhinovirus infection drives necrotic cell death in cystic fibrosis airway epithelial cells
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsApril 2020Blocking Notch3 Signaling Abolishes MUC5AC Production in Airway Epithelial Cells from Asthmatics
We demonstrate that NOTCH3 is a regulator of MUC5AC production
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsDecember 2019Azithromycin reduces airway inflammation induced by human rhinovirus in lung allograft recipients
Our data illustrate that rhinovirus infection is capable of infecting upper and lower airway epithelial cells, driving cell death and inflammation
Published research Airway Epithelial Research P4 Respiratory Health for KidsNovember 2019Early respiratory viral infections in infants with cystic fibrosis
Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsNovember 2019Oxidative stress and abnormal bioactive lipids in early cystic fibrosis lung disease
Several lipid biomarkers of early cystic fibrosis lung disease were identified, which point toward potential disease monitoring and therapeutic approaches
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsSeptember 2019Changing Prevalence of Lower Airway Infections in Young Children with Cystic Fibrosis
Aspergillus species and P. aeruginosa are commonly present in the lower airways from infancy
Cystic Fibrosis Published research Academic Biostatistics P4 Respiratory Health for KidsJuly 2019The cumulative effect of inflammation and infection on structural lung disease in early cystic fibrosis
Pulmonary inflammation in surveillance bronchoalveolar lavage has a cumulative effect on structural lung disease extent, more so than infection
Cystic Fibrosis Published research P4 Respiratory Health for KidsApril 2019Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis
These findings indicate that early CF lung disease is characterized by an increased mucus burden and inflammatory markers without infection or structural lung disease
Cystic Fibrosis Published research P4 Respiratory Health for KidsApril 2019Elastase Exocytosis by Airway Neutrophils Associates with Early Lung Damage in Cystic Fibrosis Children
Protease elastase exocytosis by airway neutrophils occurs in all cystic fibrosis children, and its cellular measure correlates with early lung damage
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsNovember 2018Predicting disease progression in cystic fibrosis
Comprehensive scores incorporating clinical, lung function, imaging and laboratory data will become essential in the future for predicting disease progression and for use in clinical trials
Cystic Fibrosis Published research P4 Respiratory Health for KidsNovember 2018Elucidating the interaction of CF airway epithelial cells and rhinovirus: Using the host-pathogen relationship to identify future therapeutic strategies
A better understanding of the innate immune responses by CF airway epithelial cells is needed to identify why viral infections are more severe in CF
Cystic Fibrosis Published research Computational Biology Airway Epithelial Research P4 Respiratory Health for KidsNovember 2018Use of a primary epithelial cell screening tool to investigate phage therapy in cystic fibrosis
This study demonstrates the feasibility of utilizing pre-clinical in vitro culture models to screen therapeutic candidates
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsNovember 2018Interleukin-1 is associated with inflammation and structural lung disease in young children with cystic fibrosis
Our data associates IL-1α with early structural lung damage in CF and suggests this pathway as a novel anti-inflammatory target
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsAugust 2018CrossTalk opposing view: Mucosal acidification does not drive early progressive lung disease in cystic fibrosis
Whether airway mucosal acidification drives early progressive lung disease is controversial
Cystic Fibrosis Published research P4 Respiratory Health for KidsJuly 2018The association between Staphylococcus aureus and subsequent bronchiectasis in children with cystic fibrosis
De novo S. aureus acquisition at age 3 is associated with later bronchiectasis and FEF25-75 in children with CF
Cystic Fibrosis Published research Academic Biostatistics Children's Lung Health P4 Respiratory Health for KidsMay 2018Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma
This study demonstrates novel intrinsic differences in tight junctions gene and protein expression between airway epithelial cells of children with and without asthma
Asthma Published research Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthMay 2018Persistent induction of goblet cell differentiation in the airways: Therapeutic approaches
Here we review the current knowledge of key molecular pathways that are dysregulated during persistent goblet cell differentiation
Published research Airway Epithelial Research P4 Respiratory Health for KidsFebruary 2018Visualisation of Multiple Tight Junctional Complexes in Human Airway Epithelial Cells
Apically located tight junctions in airway epithelium perform a fundamental role in controlling macromolecule migration through paracellular spaces.
Published research Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthJanuary 2018Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung
We aimed to delineate the effects of LPS and AMP on airway inflammation, and potential contribution to airway disease by measuring airway inflammatory responses
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2018Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatic with natural aeroallergen exposure
Asthma Published research Human Immunology Systems Immunology Airway Epithelial Research Children's Lung Health P4 Respiratory Health for KidsJanuary 2018Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic fibrosis airway epithelial cells
This study assessed an alternative approach, using a small scale halide assay that can be adapted for a personalized high throughput setting to analyze CFTR function of pAEC.
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2017Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
In this review, we consider recent evidence regarding hypoxia and sterile inflammation in cystic fibrosis airways
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsFebruary 2017Induced sputum to detect lung pathogens in young children with cystic fibrosis
we aimed to determine the sensitivity and specificity of induced sputum with and without airway clearance techniques to detect lower airway pathogens in kids.
Published researchApril 2017Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma
In this study, we aimed to use microRNAs-which are critical regulators of signaling cascades-to identify so far uncharacterized asthma pathogenesis pathways
Asthma Published research Airway Epithelial Research Respiratory Environmental HealthJune 2017Early lung disease in infants and preschool children with cystic fibrosis: What have we learned and what should we do about it?
This review summarizes what we have learned about early lung disease in children with CF and discusses the implications for clinical practice and research
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsAugust 2017Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity
In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset.
Published research Inflammation Cardiometabolic Sunhealth Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthSeptember 2017The AREST CF experience in biobanking - More than just tissues, tubes and time.
Research to further improve outcomes for people with CF is dependent upon well characterised, archived and accessible clinical specimens.
Cystic Fibrosis Published research P4 Respiratory Health for KidsSeptember 2017Multiple-breath washout outcomes are sensitive to inflammation and infection in children with cystic fibrosis
The lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsSeptember 2017Air trapping in early cystic fibrosis lung disease-Does CT tell the full story?
Mosaic attenuation on expiratory chest computed tomography (CT) is common in early life cystic fibrosis (CF) and often referred to as "air trapping"
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsNovember 2017Effect of posture on lung ventilation distribution and associations with structure in children with cystic fibrosis
Background: We assessed the effect of posture on ventilation distribution and the impact on associations with structural lung disease.
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsNovember 2017Airway surface liquid pH is not acidic in children with cystic fibrosis
Modulation of ASL pH has been proposed as a therapy for CF. However, evidence that ASL pH is reduced in CF is limited and conflicting.
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsNovember 2017Quantitative assessment of airway dimensions in young children with cystic fibrosis lung disease using chest computed tomography
To evaluate lung disease progression using AA dimensions on chest CT over 2-years in young CF patients longitudinally and compare to disease controls.
Cystic Fibrosis Published research P4 Respiratory Health for KidsDecember 2017Conditionally reprogrammed primary airway epithelial cells maintain morphology, lineage and disease specific functional characteristics
Here, we show that conditionally reprogrammed airway epithelial cells (CRAECs) can be established from both healthy and diseased phenotypes.
Published research Airway Epithelial Research P4 Respiratory Health for KidsDecember 2016Respiratory function and symptoms in young preterm children in the contemporary era
Preterm children have worse lung function than healthy controls
Published research Children's Lung Health P4 Respiratory Health for KidsNovember 2016Impaired airway epithelial cell responses from children with asthma to rhinoviral infection
Human rhinovirus infection delays repair and inhibits apoptotic processes in epithelial cells from non-asthmatic and asthmatic children
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsOctober 2016Reduced transforming growth factor β1 (TGF-β1) in the repair of airway epithelial cells of children with asthma
Reduced TGF-β1 levels in paediatric asthmatic airway epithelial cells directly contribute to the dysregulated repair in these cells
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsOctober 2016Of pigs, mice, and men: Understanding early triggers of cystic fibrosis lung disease
Understanding early triggers of Cystic Fibrosis Lung Disease
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsOctober 2016Effect of human rhinovirus infection on airway epithelium tight junction protein disassembly and transepithelial permeability
HRV-1B infection directly alters human airway epithelial TJ expression leading to increased epithelial permeability potentially via antiviral response of IL-15
Published research Systems Immunology Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthSeptember 2016The genetic and epigenetic landscapes of the epithelium in asthma
Genetic factors in airway epithelial cells that are functionally associated with asthma pathogenesis
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsAugust 2016Dissecting the regulation of bile-induced biofilm formation in staphylococcus aureus
Wall teichoic acid may be important for protecting S. aureus against exposure to bile
Cystic Fibrosis Published research P4 Respiratory Health for KidsJuly 2016Bile signalling promotes chronic respiratory infections and antibiotic tolerance
Bile acid signalling is a leading trigger for the development of chronic phenotypes underlying the pathophysiology of chronic respiratory disease
Cystic Fibrosis Published research P4 Respiratory Health for KidsJanuary 2016Alpha-1 antitrypsin mitigates the inhibition of airway epithelial cell repair by neutrophil elastase
Free NE activity is deleterious for epithelial homeostasis and support the hypothesis that proteases in the airway contribute to CF structural lung disease
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2016Airway epithelial repair in health and disease: Orchestrator or simply a player?
This review attempts to highlight migration-specific and cell-extracellular matrix (ECM) aspects of repair used by epithelial cells
Asthma Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2016Lung Clearance Index and Structural Lung Disease on Computed Tomography in Early Cystic Fibrosis
Lung clearance index may be a useful surveillance tool to monitor structural lung disease in preschool and school-age children with cystic fibrosis
Cystic Fibrosis Published researchSeptember 2015Impact of lung disease on respiratory impedance in young children with cystic fibrosis
The present study investigated whether lung function measured by forced oscillation technique would be impaired in the presence of infection,...
Cystic Fibrosis Published research Academic Biostatistics Children's Lung Health P4 Respiratory Health for KidsSeptember 2015Progressive ventilation inhomogeneity in infants with cystic fibrosis after pulmonary infection
This study aimed to determine how pulmonary inflammation & infection impacts on ventilation distribution throughout early life in people with cystic fibrosis.
Cystic Fibrosis Published research Academic Biostatistics Children's Lung Health P4 Respiratory Health for KidsAugust 2015Disruption of β-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair.
The airway epithelium of both children and adults with asthma is relatively undifferentiated characterized by a significantly increased proportion of...
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2015Biomarkers in paediatric Cystic Fibrosis lung disease
Biomarkers in cystic fibrosis are used for the measurement of cystic fibrosis transmembrane regulator function in order to diagnose cystic fibrosis,...
Cystic Fibrosis Published research P4 Respiratory Health for KidsApril 2015Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis
The aim of this study was to assess if MMP activation positively correlates with neutrophil elastase activity, disease severity and bronchiectasis in young...
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsApril 2015Productive infection of human embryonic stem cell-derived nkx2.1+ respiratory progenitors with human rhinovirus.
Our experiments provide proof of principle for the use of PSC-derived respiratory epithelial cells in the study of cell-virus interactions.
Published research Infectious Diseases Airway Epithelial Research P4 Respiratory Health for KidsApril 2015Respiratory tract exacerbations revisited: Ventilation, inflammation, perfusion, and structure (VIPS) monitoring to redefine treatment
For cystic fibrosis (CF) patients older than 6 years there are convincing data that suggest respiratory tract exacerbations (RTE) play an important role in...
Cystic Fibrosis Published research P4 Respiratory Health for KidsMarch 2015Early pulmonary inflammation and lung damage in children with cystic fibrosis
Airway inflammation and infection are present from early in life, often before children are symptomatic.
Cystic Fibrosis Published research P4 Respiratory Health for KidsMarch 2015PRAGMA-CF. A Quantitative Structural Lung Disease Computed Tomography Outcome in Young Children with Cystic Fibrosis
Chest computed tomography (CT) is the gold standard for demonstrating cystic fibrosis (CF) airway disease. However, there are no standardized outcome...
Cystic Fibrosis Published research P4 Respiratory Health for KidsDecember 2014Feasibility of parental collected nasal swabs for virus detection in young children with cystic fibrosis
No evidence to demonstrate relationships with symptoms and viruses, prolonged symptoms, prolonged shedding or patterns of virus infections in CF
Cystic Fibrosis Published research P4 Respiratory Health for KidsNovember 2014Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis
We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung...
Published research Academic Biostatistics Children's Lung Health P4 Respiratory Health for KidsNovember 2014House dust mite induced lung inflammation does not alter circulating vitamin D levels
We hypothesized that allergic inflammation decreases the level of circulating 25(OH)D and tested this using a mice model of house dust mite (HDM) induced...
Published research Vitamin D and Sunlight Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthNovember 2014Determinants of culture success in an airway epithelium sampling program of young children with cystic fibrosis
Determinants of culture success through retrospective analysis of a program of routinely brushing children with Cystic Fibrosis airway disease
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJune 2014Early cystic fibrosis lung disease
This paper is about lung disease in patients with cyctic Fibrosis and prevention strategies to slow the onset of lung disease.
Cystic Fibrosis Published research Bronchiolitis Nutrition P4 Respiratory Health for KidsMarch 2014Multi-modality monitoring of cystic fibrosis lung disease: the role of chest computed tomography
Stratification of monitoring protocols based on the risk profile of the patient can help us in the future to better care for people with Cystic Fibrosis.
Cystic Fibrosis Published research P4 Respiratory Health for KidsJanuary 2014Parental experiences of early pulmonary surveillance for children with cystic fibrosis: A research proposal for improved family psychosocial outcomes
The proposed study intends to explore parental experiences, including coping, related to their child's involvement in the early surveillance program.
Cystic Fibrosis Published research P4 Respiratory Health for KidsDecember 2013Transcription factor p63 regulates key genes and wound repair in human airway epithelial Basal cells
The airway epithelium in asthma displays altered repair and incomplete barrier formation.
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsNovember 2013The safety and feasibility of the inhaled mannitol challenge test in young children
Mannitol challenge tests are used clinically to diagnose asthma and, in particular, exercise-induced broncoconstriction (EIB) in adults and children above 6...
Asthma Published research Children's Lung Health P4 Respiratory Health for KidsOctober 2013Assessment of early bronchiectasis in young children with cystic fibrosis is dependent on lung volume
The aim of this study was to determine whether assessment of early CT scan-detected bronchiectasis in young children with cystic fibrosis (CF) depends on...
Cystic Fibrosis Published research Academic Biostatistics P4 Respiratory Health for KidsSeptember 2013Chest computed tomography: a validated surrogate endpoint of cystic fibrosis lung disease?
Clinical trials for the treatment of cystic fibrosis (CF) lung disease are important to test and optimise new therapeutic interventions.
Cystic Fibrosis Published research P4 Respiratory Health for KidsJuly 2013Expiratory flow limitation and breathing strategies in overweight adolescents during submaximal exercise
Young people who are overweight/obese are more likely to display expFL during submaximal exercise compared with children of healthy weight.
Published research Children's Lung Health P4 Respiratory Health for KidsJuly 2013Distribution of Early Structural Lung Changes due to Cystic Fibrosis Detected with Chest Computed Tomography
To examine the distribution of early structural lung changes in clinically stable infants and young children with cystic fibrosis using chest computed...
Cystic Fibrosis Published research Academic Biostatistics P4 Respiratory Health for KidsJune 2013Novel end points for clinical trials in young children with cystic fibrosis
Cystic fibrosis (CF) lung disease commences early in the disease progression and is the most common cause of mortality.
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsMay 2013Risk factors for bronchiectasis in children with cystic fibrosis
We sought to determine risk factors for the onset of bronchiectasis, using data collected by the Australian Respiratory Early Surveillance Team for Cystic...
Cystic Fibrosis Published research Bronchiolitis P4 Respiratory Health for KidsDecember 2012Regional Differences in Susceptibiity of Bronchial Epithelium to Mesenchymal Transition and Inhibition by the Macrolide Antibiotic Azithromycin
Dysregulated repair following epithelial injury is a key forerunner of disease in many organs, and the acquisition of a mesenchymal phenotype by the injured...
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsSeptember 2012Characterization of maximal respiratory pressures in healthy children
Measurements of maximal voluntary inspiratory (Pi max) and expiratory (Pe max) pressures are used in the management of respiratory muscle disease...
Published research Children's Lung Health P4 Respiratory Health for KidsSeptember 2012DNA Methylation Profiles of Airway Epithelial Cells and PBMCs from Healthy, Atopic and Asthmatic Children
Allergic inflammation is commonly observed in a number of conditions that are associated with atopy including asthma, eczema and rhinitis.
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJune 2012Suppression of adrenomedullin contributes to vascular leakage and altered epithelial repair during asthma
The anti-inflammatory peptide, adrenomedullin (AM), and its cognate receptor are expressed in lung tissue, but its pathophysiological significance in airway...
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsJune 2012Progression of early structural lung disease in young children with cystic fibrosis assessed using CT
Cross-sectional studies implicate neutrophilic inflammation and pulmonary infection as risk factors for early structural lung disease in infants and young...
Cystic Fibrosis Published research Academic Biostatistics P4 Respiratory Health for KidsJanuary 2012Clinical investigation of respiratory system admittance in preschool children
We compared the ability of Ars, to standard oscillatory outcomes, to determine respiratory disease and differentiate responses to inhaled bronchial challenges.
Published research Children's Lung Health P4 Respiratory Health for KidsJanuary 2012Hypoglycemia does not change the threshold for arousal from sleep in adolescents with type 1 diabetes
In adolescents with type 1 diabetes, hypoglycemia does not impair arousal from slow-wave sleep induced by an external auditory stimulus.
Diabetes (Type 1) Published research Diabetes and Obesity P4 Respiratory Health for KidsAugust 2011Air Trapping on Chest CT Is Associated with Worse Ventilation Distribution in Infants with Cystic Fibrosis
In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution.
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsJuly 2011Defective function at the epithelial junction: A novel therapeutic frontier in asthma?
The airway epithelium forms a highly regulated physical barrier that normally prevents invasion of inhaled pathogens and allergens from the airway lumen.
Asthma Published research P4 Respiratory Health for KidsJuly 2011Infection, inflammation,and lung function decline in infants with cystic fibrosis
Better understanding of evolution of lung function in infants with cystic fibrosis...
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsJune 2011Exciting new clinical trials in cystic fibrosis: Infants need not apply
The recent announcement of the negative results of the TIGER- 2 phase 3 study of denufosol tetrasodium
Cystic Fibrosis Published research P4 Respiratory Health for KidsJune 2011The airway epithelium is a direct source of matrix degrading enzymes in bronchiolitis obliterans syndrome
Long-term survival after lung transplantation is hindered by the development of bronchiolitis obliterans syndrome (BOS).
Published research Airway Epithelial Research P4 Respiratory Health for KidsMay 2011Evolution of pulmonary inflammation and nutritional status in infants and young children with cystic fibrosis
Improved nutrition is the major proven benefit of newborn screening programmes for cystic fibrosis (CF) and is associated with better clinical outcomes.
Cystic Fibrosis Published research Early Childhood DevelopmentMay 2011Bronchial brushings for investigating airway inflammation and remodelling
Asthma is the commonest medical cause for hospital admission for children in Australia, affects more than 300 million people worldwide, and is incurable...
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsFebruary 2011Innate inflammatory responses of pediatric cystic fibrosis airway epithelial cells: Effects of nonviral and viral stimulation
There is controversy regarding whether cystic fibrosis (CF) airway epithelial cells (AECs) are intrinsically proinflammatory.
Cystic Fibrosis Published research Airway Epithelial Research P4 Respiratory Health for KidsJanuary 2011Randomised controlled trials in cystic fibrosis: What, when and how?
The major morbidity and mortality from cystic fibrosis (CF) comes from progressive lung disease with bronchiectasis leading to respiratory failure
Cystic Fibrosis Published research Academic Biostatistics P4 Respiratory Health for KidsJuly 2010Expression of bronchodilator response using forced oscillation technique measurements: absolute versus relative
Expression of bronchodilator response using forced oscillation technique measurements: absolute versus relative
Published research Children's Lung Health P4 Respiratory Health for KidsMay 2010Lung function testing in preschool-aged children with cystic fibrosis in the clinical setting
This study investigated the nature and prevalence of atypical pain responses in Rett syndrome and their relationships with specific MECP2 mutations.
Cystic Fibrosis Published research Children's Lung Health P4 Respiratory Health for KidsMay 2010Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium
In human asthma, and experimental allergic airways disease in mice, antigen-presenting cells and CD4(+) effector cells at the airway mucosa orchestrate, and CD4
Asthma Published research Airway Epithelial Research P4 Respiratory Health for KidsOctober 2009Successful establishment of primary small airway cell cultures in human lung transplantation
The study of small airway diseases such as post-transplant bronchiolitis obliterans syndrome (BOS) is hampered by the difficulty in assessing peripheral airway
Published research Bronchiolitis Airway Epithelial Research P4 Respiratory Health for Kids