Associate Professor Anthony Kicic

Estimating the Impact And Costs of Antimicrobial Resistance (AMR) at Perth Children’s Hospital

AMR is a rapidly growing challenge and has been identified as one of the World Health Organizations top 10 global health threats, with the potential to undo many of the health gains observed over the last century.

Kids Easy Breathing Study

As both bronchiolitis and bronchiectasis are diseases of the airway surface, we will comprehensively study the airway surface and factors affecting the airway surface in infants hospitalised with bronchiolitis.

Compound Repurposing Into Novel Therapeutics In COVID-19 At risk Lungs (CRITICAL Study)

A pilot study into assessing the danger of heated-tobacco-products

SYNERGY CF: Getting the best start to life - preventing early cystic fibrosis lung disease by solving the host-inflammation infection conundrum

Mechanisms of Acute Viral Respiratory Illness in Children (MAVRIC)

Large numbers of children need emergency medical treatment each year for respiratory illnesses, particularly for wheezing and asthma.

WA Epithelial Research Program for Childhood Respiratory Diseases

Vulnerable from the first breath - epithelial dysfunction and respiratory outcomes in children

Epithelial Drivers of Neutrophil Plasticity in Early Cystic Fibrosis Lung Disease

Developing a novel therapeutic pipeline for antibiotic resistant bacterial lung infection in children: investigating and assessing the potential phage therapy

Defective cell migration as a mechanism of dysregulated asthmatic airway repair

Cultures of HRV-C for investigations of pathogenesis in children

Children’s regenerative and genetic medicine program

A tonsil organ model to evaluate carriage, disease mechanisms and therapeutic interventions for the treatment and prevention of Group A Streptococcus infections

Improved diagnosis, treatment and prevention of recurrent tonsillitis

Defining Group A Streptococcus interaction with the tonsil epithelium to inform vaccine development

Using Systems Biology to understand asthma exacerbations and develop better treatments

Development of a screening tool to identify safer biodiesels

ARIEL study

Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae

The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. 

Phage therapy to treat cystic fibrosis Burkholderia cepacia complex lung infections: perspectives and challengesge

Burkholderia cepacia complex is a cause of serious lung infections in people with cystic fibrosis, exhibiting extremely high levels of antimicrobial resistance. These infections are difficult to treat and are associated with high morbidity and mortality. 

Real world effectiveness of early ensitrelvir treatment in patients with SARS-CoV-2, a retrospective case series

Ensitrelvir, a 3C-like protease inhibitor, received emergency approval in Japan in November 2022 for treating non-hospitalized patients with mild-to-moderate COVID-19. However, confirmation of its real-world clinical effectiveness is limited.

Real time monitoring of respiratory viral infections in cohort studies using a smartphone app

Cohort studies investigating respiratory disease pathogenesis aim to pair mechanistic investigations with longitudinal virus detection but are limited by the burden of methods tracking illness over time. In this study, we explored the utility of a purpose-built AERIAL TempTracker smartphone app to assess real-time data collection and adherence monitoring and overall burden to participants, while identifying symptomatic respiratory illnesses in two birth cohort studies.

Lentiviral vector gene therapy and CFTR modulators show comparable effectiveness in cystic fibrosis rat airway models

Mutation-agnostic treatments such as airway gene therapy have the potential to treat any individual with cystic fibrosis (CF), irrespective of their CF transmembrane conductance regulator (CFTR) gene variants. The aim of this study was to employ two CF rat models, Phe508del and CFTR knockout to assess the comparative effectiveness of CFTR modulators and lentiviral vector-mediated gene therapy. 

Transcriptomic analysis of primary nasal epithelial cells reveals altered interferon signalling in preterm birth survivors at one year of age

Many survivors of preterm birth (<37 weeks gestation) have lifelong respiratory deficits, the drivers of which remain unknown. Influencers of pathophysiological outcomes are often detectable at the gene level and pinpointing these differences can help guide targeted research and interventions. This study provides the first transcriptomic analysis of primary nasal airway epithelial cells in survivors of preterm birth at approximately 1 year of age.

Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia

Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii-associated pneumonia.

The respiratory health effects of acute in vivo diesel and biodiesel exhaust in a mouse model

Biodiesel, a renewable diesel fuel that can be created from almost any natural fat or oil, is promoted as a greener and healthier alternative to commercial mineral diesel without the supporting experimental data to back these claims. The aim of this research was to assess the health effects of acute exposure to two types of biodiesel exhaust, or mineral diesel exhaust or air as a control in mice.

Antenatal creatine supplementation reduces persistent fetal lung inflammation and oxidative stress in an ovine model of chorioamnionitis

Chorioamnionitis is a common antecedent of preterm birth and induces inflammation and oxidative stress in the fetal lungs. Reducing inflammation and oxidative stress in the fetal lungs may improve respiratory outcomes in preterm infants. Creatine is an organic acid with known anti-inflammatory and antioxidant properties.

Exploring the Complexity of the Human Respiratory Virome through an In Silico Analysis of Shotgun Metagenomic Data Retrieved from Public Repositories

Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases’ pathogenesis.

Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial

Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries. 

Exploring indoor and outdoor dust as a potential tool for detection and monitoring of COVID-19 transmission

This study investigated the potential of using SARS-CoV-2 viral concentrations in dust as an additional surveillance tool for early detection and monitoring of COVID-19 transmission. Dust samples were collected from 8 public locations in 16 districts of Bangkok, Thailand, from June to August 2021.

Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection

Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. 

Tracing the transmission of mpox through wastewater surveillance in Southeast Asia

High population density and tourism in Southeast Asia increase the risk of mpox due to frequent interpersonal contacts. Our wastewater surveillance in six Southeast Asian countries revealed positive signals for Monkeypox virus (MPXV) DNA, indicating local transmission. This alerts clinicians and helps allocate resources like testing, vaccines and therapeutics in resource-limited countries.

Stability Considerations for Bacteriophages in Liquid Formulations Designed for Nebulization

Pulmonary bacterial infections present a significant health risk to those with chronic respiratory diseases including cystic fibrosis and chronic-obstructive pulmonary disease. With the emergence of antimicrobial resistance, novel therapeutics are desperately needed to combat the emergence of resistant superbugs.

Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiella pneumoniae infections

Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be addressed urgently. Here, we explored a Ca-EDTA combination with aztreonam or ceftazidime-avibactam in vitro and in vivo against diverse CPKp clinical isolates.

COVID-19 monitoring with sparse sampling of sewered and non-sewered wastewater in urban and rural communities

Equitable SARS-CoV-2 surveillance in low-resource communities lacking centralized sewers is critical as wastewater-based epidemiology (WBE) progresses. However, large-scale studies on SARS-CoV-2 detection in wastewater from low-and middle-income countries is limited because of economic and technical reasons.

Defining the pediatric response to SARS-CoV-2 variants

The global population has been severely affected by the coronavirus disease 2019 (COVID-19) pandemic, however, with older age identified as a risk factor, children have been underprioritized. This article discusses the factors contributing to the less severe response observed in children following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including, differing viral entry receptor expression and immune responses.

Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

For those born with cystic fibrosis (CF), hyper-concentrated mucus with a dysfunctional structure significantly impacts CF airways, providing a perfect environment for bacterial colonization and subsequent chronic infection. Early treatment with antibiotics limits the prevalence of bacterial pathogens but permanently alters the CF airway microenvironment, resulting in antibiotic resistance and other long-term consequences.

Respiratory Health Effects of In Vivo Sub-Chronic Diesel and Biodiesel Exhaust Exposure

Biodiesel, which can be made from a variety of natural oils, is currently promoted as a sustainable, healthier replacement for commercial mineral diesel despite little experimental data supporting this. The aim of our research was to investigate the health impacts of exposure to exhaust generated by the combustion of diesel and two different biodiesels.

Pseudomonas 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.

Phage Therapy as an Alternative Treatment Modality for Resistant Staphylococcus aureus Infections

The production and use of antibiotics increased significantly after the Second World War due to their effectiveness against bacterial infections. However, bacterial resistance also emerged and has now become an important global issue.

Complete 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.

Complete 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.

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.

Genome 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.

Bacteriophage: 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.

Multiple traces of monkeypox detected in non-sewered wastewater with sparse sampling from a densely populated metropolitan area in Asia

The monkeypox virus is excreted in the feces of infected individuals. Therefore, there is an interest in using viral load detection in wastewater for sentinel early surveillance at a community level and as a complementary approach to syndromic surveillance.

Living with lung disease: experimental models to assess the long-term effects of prematurity

Laboratory models provide an important tool in helping to understand the cellular and molecular drivers of respiratory disease. Many animal models exist that model the neonatal outcomes of preterm birth.

Biodiesel feedstock determines exhaust toxicity in 20% biodiesel: 80% mineral diesel blends

To address climate change concerns, and reduce the carbon footprint caused by fossil fuel use, it is likely that blend ratios of renewable biodiesel with commercial mineral diesel fuel will steadily increase, resulting in biodiesel use becoming more widespread.

Biodiesel Exhaust Toxicity with and without Diethylene Glycol Dimethyl Ether Fuel Additive in Primary Airway Epithelial Cells Grown at the Air-Liquid Interface

Biodiesel usage is increasing steadily worldwide as the push for renewable fuel sources increases. The increased oxygen content in biodiesel fuel is believed to cause decreased particulate matter (PM) and increased nitrous oxides within its exhaust.

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate.

High prevalence of mgrB-mediated colistin resistance among carbapenem-resistant Klebsiella pneumoniae is associated with biofilm formation, and can be overcome by colistin-EDTA combination therapy

The global prevalence of colistin-resistant Klebsiella pneumoniae (ColRkp) facilitated by chromosomal and plasmid-mediated Ara4N or PEtN-remodeled LPS alterations has steadily increased with increased colistin usage for treating carbapenem-resistant K. pneumoniae (CRkp).

Macrophage 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.

AI-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.

Investigating 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.

SLC6A14 Impacts Cystic Fibrosis Lung Disease Severity via mTOR and Epithelial Repair Modulation

Cystic fibrosis (CF), due to pathogenic variants in CFTR gene, is associated with chronic infection/inflammation responsible for airway epithelium alteration and lung function decline. Modifier genes induce phenotype variability between people with CF (pwCF) carrying the same CFTR variants. Among these, the gene encoding for the amino acid transporter SLC6A14 has been associated with lung disease severity and age of primary airway infection by the bacteria Pseudomonas aeruginosa.

Toxicity of different biodiesel exhausts in primary human airway epithelial cells grown at air-liquid interface

Biodiesel is created through the transesterification of fats/oils and its usage is increasing worldwide as global warming concerns increase. Biodiesel fuel properties change depending on the feedstock used to create it.

Primary 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.

In Vitro primary human airway epithelial whole exhaust exposure

The method outlined in this article is a customization of the whole exhaust exposure method generated by Mullins et al. (2016) using reprogrammed primary human airway epithelial cells as described by Martinovich et al. (2017). It has been used successfully to generate recently published data (Landwehr et al. 2021). The goal was to generate an exhaust exposure model where exhaust is collected from a modern engine, real-world exhaust concentrations are used and relevant tissues exposed to assess the effects of multiple biodiesel exposures.

Nasal airway epithelial repair after very preterm birth

Nasal epithelial cells from very preterm infants have a functional defect in their ability to repair beyond the first year of life, and failed repair may be associated with antenatal steroid exposure.

The Role of Subinhibitory Concentrations of Daptomycin and Tigecycline in Modulating Virulence in Staphylococcus aureus

Staphylococcus aureus (S. aureus) infections are notoriously complicated by the ability of the organism to grow in biofilms and are difficult to eradicate with antimicrobial therapy.

Exacerbation of chronic cigarette-smoke induced lung disease by rhinovirus in mice

A significant proportion of chronic obstructive pulmonary disease exacerbations are strongly associated with rhinovirus infection (HRV). In this study, we combined long-term cigarette smoke exposure with HRV infection in a mouse model.

Dysregulated 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.

Viral Induced Effects on a Vulnerable Epithelium; Lessons Learned From Paediatric Asthma and Eosinophilic Oesophagitis

The epithelium is integral to the protection of many different biological systems and for the maintenance of biochemical homeostasis. Emerging evidence suggests that particular children have epithelial vulnerabilities leading to dysregulated barrier function and integrity, that resultantly contributes to disease pathogenesis.

Development 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.

Phage 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.

Cystic 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.

Previous 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.

Fuel feedstock determines biodiesel exhaust toxicity in a human airway epithelial cell exposure model

Biodiesel is promoted as a sustainable replacement for commercial diesel. Biodiesel fuel and exhaust properties change depending on the base feedstock oil/fat used during creation. The aims of this study were, for the first time, to compare the exhaust exposure health impacts of a wide range of biodiesels made from different feedstocks and relate these effects with the corresponding exhaust characteristics.

Overcoming 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.

Pseudomonas 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.

Changes 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.

ACE2 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.

Intrauterine growth restriction predisposes to airway inflammation without disruption of epithelial integrity in postnatal male mice

Evidence from animal models demonstrate that intrauterine growth restriction (IUGR) alters airway structure and function which may affect susceptibility to disease. Airway inflammation and dysregulated epithelial barrier properties are features of asthma which have not been examined in the context of IUGR.

COPD-related modification to the airway epithelium permits intracellular residence of nontypeable haemophilus influenzae

Our findings indicate that COPD, cigarette smoke and macrolide antibiotics potentiate the susceptibility to persistent intracellular NTHi

Azithromycin 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

Assessing 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

Epithelial 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

Rhinovirus 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

Progress in Model Systems of Cystic Fibrosis Mucosal Inflammation to Understand Aberrant Neutrophil Activity

Here we examine the latest findings of neutrophils in pediatric CF lung disease and proposed mechanisms of their pathogenicity

Blocking Notch3 Signaling Abolishes MUC5AC Production in Airway Epithelial Cells from Asthmatics

We demonstrate that NOTCH3 is a regulator of MUC5AC production

Azithromycin 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

Soy Biodiesel Exhaust is More Toxic than Mineral Diesel Exhaust in Primary Human Airway Epithelial Cells

Exposure to biodiesel exhaust resulted in significantly greater cell death and a greater release of immune mediators compared to both air controls and ULSD exhaust

Preterm birth: Born too soon for the developing airway epithelium

This review examines the consequences of preterm birth on the airway epithelium and explores the clinical relevance of currently available models

The Contribution of Geogenic Particulate Matter to Lung Disease in Indigenous Children

The aim of this study was to assess the relationship between dust levels and health in Indigenous children in Western Australia

Elastase 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

Ground zero—the airway epitheliumNew Page

This chapter will discuss the structure of the airway highlighting the now broad number of cell types that comprise it

Human Primary Epithelial Cell Models: Promising Tools in the Era of Cystic Fibrosis Personalized Medicine

In this Review, we consolidate the latest updates in the development of primary epithelial cellular model systems relevant for cystic fibrosis

Use 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

Elucidating 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

Interleukin-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

Effects 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

Persistent 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

Visualisation 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.

Accumulation 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

Assessment 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.

Conditionally 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.

The potential of phage therapy in cystic fibrosis

This review summarises the phage-microbe-human lung interactions in CF that must be addressed to successfully develop and deliver phage to CF airways

Airway 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.

The 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.

Vitamin 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.

Pulmonary 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

Hypoxia 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

Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells

Canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared with ULSD exhaust exposure

Impaired 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

Effect 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

Reduced transforming growth factor β1 (TGF-β1) in the repair of airway epithelial cells of children with asthma

Evidence into the role of TGF-β1 in airway epithelial repair in asthma is still controversial. This study tested the hypothesis that the reduced TGF-β1 levels previously observed in paediatric asthmatic airway epithelial cells directly contribute to the dysregulated repair seen in these cells.

Of pigs, mice, and men: Understanding early triggers of cystic fibrosis lung disease

Understanding early triggers of Cystic Fibrosis Lung Disease

The genetic and epigenetic landscapes of the epithelium in asthma

Genetic factors in airway epithelial cells that are functionally associated with asthma pathogenesis

Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease

Vitamin D deficiency exacerbates house dust mite-induced inflammation and alterations in lung structure and function

Alpha-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

Airway 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

Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice

Early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice

Pressurised metered dose inhaler-spacer technique in young children improves with video instruction

Repeated video instruction over time improves inhaler technique in young children

Disruption 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...

Biodiesel exhaust: The need for a systematic approach to health effects research

Biodiesel is a generic term for fuel that can be made from virtually any plant or animal oil via transesterification of triglycerides with an alcohol...

Matrix 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...

Productive 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.

House 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...

Determinants 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

Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells

Our results show that canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared...

Route of exposure alters inflammation and lung function responses to diesel exhaust

In this study, we compared the physiological consequences of short-term exposure to diesel exhaust via inhalation to those due to exposure to the same diesel...

Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice

In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to...

Transcription 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.

Regional 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...

DNA 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.

Suppression 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...

The 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).

Bronchial 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...

Innate 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.

Decreased 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

Successful 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