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Publications (193)
Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammato...
Rationale:
A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6 through 11 years with cystic fibrosis and ≥1 F508del-CFTR allele.
Objectives:
To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial.
Method...
Survival statistics, estimated using data from national cystic fibrosis (CF) registries, inform the CF community and monitor disease progression. This study aimed to estimate survival among people with CF in Australia and to identify factors associated with survival. This population-based cohort study used prospectively collected data from 23 Austr...
Background
We aimed to assess the direct protective effect of 13 valent pneumococcal conjugate vaccine (13vPCV) against invasive pneumococcal pneumonia (IPP; including pneumonia and empyema) in children using a nation-wide case-control study across 11 paediatric tertiary hospitals in Australia.
Methods
Children < 18 years old admitted with pneumon...
Survival statistics, estimated using data from national cystic fibrosis (CF) registries, inform the CF community and monitor disease progression. This study aimed to estimate survival among people with CF in Australia and to identify factors associated with survival. This population-based cohort study used prospectively collected data from 23 Austr...
Background
Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung...
Cystic fibrosis is a genetic disease with multisystem
involvement. Orkambi (Lumacaftor/Ivacaftor) is approved for patients
6 years and above with homozygous Phe508del in Australia and is not
recommended in those with severe liver disease who were excluded from
the trials. Limited studies have shown an increased medication exposure
(AUC0-12hr by app...
Background
Tezacaftor/ivacaftor is a CFTR modulator approved to treat people with cystic fibrosis (pwCF) who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function mutation (F/RF). This randomized, double-blind, placebo-controlled Phase 3 study evaluated the efficacy, safety, tolerability, and pharmacokinetics (P...
Background
The impact of early cystic fibrosis (CF) on health-related quality-of-life (HRQOL) in preschool children is poorly characterised, and data on relationships between HRQOL and health outcomes in young children with CF are limited. We aimed to characterise and compare parent-proxy and child-reported HRQOL and evaluate relationships with cli...
Clinical registries that monitor and review outcomes for patients with cystic fibrosis have existed internationally for many decades. However, their purpose continues to evolve and now includes the capability to support clinical effectiveness research, clinical trials and Phase IV studies, and international data comparisons and projects. To achieve...
Background:
Lumacaftor/ivacaftor (LUM/IVA) improves outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV1 > 40%. There is limited safety or efficacy data in patients with ppFEV1 < 40%. We determined whether LUM/IVA in patients with ppFEV1 < 40 would reduce the rate of pulmonary exacerbations.
Methods:
This was a case con...
Background:
Early diagnosis and treatment of lower respiratory tract infections are the mainstay of management of lung disease in cystic fibrosis. When sputum samples are unavailable, treatment relies mainly on cultures from oropharyngeal specimens; however, there are concerns regarding the sensitivity of these to identify lower respiratory organi...
Background:
Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and previously updated in 2010 and 2013....
Background:
Bronchoalveolar lavage (BAL) is a potentially useful outcome measure for clinical trials in children with CF but its use is limited by variations in approach internationally. We sought to determine if pooling adversely affected the diagnostic properties of BAL.
Methods:
Children undergoing bronchoscopy for clinical reasons were inclu...
The paediatric intensive care unit (PICU) provides care to critically ill neonates, infants and children. These patients are vulnerable and susceptible to the environment surrounding them, yet there is little information available on indoor air quality and factors affecting it within a PICU. To address this gap in knowledge we conducted continuous...
Background
Lumacaftor and ivacaftor combination treatment showed efficacy in patients aged 12 years or older with cystic fibrosis homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR) in placebo-controlled studies and patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR in an open-label study. We rep...
Exaggerated neutrophil-dominated inflammation is an integral component of cystic fibrosis (CF) lung disease, but why this occurs and why it is not switched-off normally is unclear. Macrophages play important roles in initiation and resolution of pulmonary inflammation but have not been extensively studied in CF.
Using an ex vivo model we developed...
Background
The ‘General Level Framework’ (GLF) has been used for many years as a tool for competency evaluation and feedback using direct observation of clinical practice; however, its use in the paediatric environment has not been investigated.AimTo identify the strengths and training and development needs for paediatric pharmacists using the GLF....
Background
Lumacaftor (LUM) increases the quantity of functional cell-surface F508del-CFTR. Ivacaftor (IVA) increases the open probability of cell-surface F508del-CFTR. In primary cell cultures, LUM/IVA combination increased chloride transport more than either agent alone.
Methods
Two randomized, double-blind, placebo-controlled phase 3 studies ev...
Background
Lumacaftor (LUM) increases the quantity of functional cell-surface F508del-CFTR. Ivacaftor (IVA) increases the open probability of cell-surface F508del-CFTR. In vitro, LUM/IVA in combination increased chloride transport more than either alone. Two randomized, double-blind, placebo-controlled phase 3 studies evaluated the efficacy and saf...
BACKGROUND
Cystic fibrosis is a life-limiting disease that is caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Phe508del is the most common CFTR mutation.
METHODS
We conducted two phase 3, randomized, double-blind, placebo-controlled studies that were designed to assess the effects of lum...
We describe Pseudomonas aeruginosa acquisitions in children with cystic fibrosis (CF) aged ≤5-years, eradication treatment efficacy, and genotypic relationships between upper and lower airway isolates and strains from non-CF sources.
Of 168 CF children aged ≤5-years in a bronchoalveolar lavage (BAL)-directed therapy trial, 155 had detailed microbio...
Background
Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, is approved for the treatment of patients with cystic fibrosis aged 6 years or older with Gly551Asp-CFTR. We assessed the safety and efficacy of ivacaftor during 96 weeks of PERSIST in patients with cystic fibrosis who completed a previous 48-week, place...
Ivacaftor is an oral bioavailable potentiator of the cystic fibrosis transmembrane conductance regulator protein. It is the first therapeutic agent that has been registered for clinical use which targets the basic defect in people with cystic fibrosis who carry a G551D mutation or other rarer specific gating mutations. Clinical trials have shown co...
AimTo compare adverse medication events (AMEs) reported in children, via the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) coding with events reported via other data sources.MethodAME reports were retrieved using codes Y40–Y59 and X40–X44 over 6 months. Patients’ charts were manually reviewe...
Background
Use of inhaled tobramycin therapy for treatment of Pseudomonas aeruginosa infections in young children with cystic fibrosis (CF) is increasing. Safety data for pre-school children are sparse.
Methods
The aim of this study was to assess the safety of tobramycin solution for inhalation (TOBI®-TSI) administered twice daily for 2 months/cou...
Background
Molecular typing is integral for identifying Pseudomonas aeruginosa strains that may be shared between patients with cystic fibrosis (CF). We conducted a side-by-side comparison of two P. aeruginosa genotyping methods utilising informative-single nucleotide polymorphism (SNP) methods; one targeting 10 P. aeruginosa SNPs and using real-ti...
Objectives
The aim of this study was to explore perceptions and attitudes of Australian paediatric pharmacists about advanced pharmacy practice and to identify suitable methods of assessment for this level of practice.Methods
Four focus groups (with 31 participants) were held in 2012 with Australian hospital pharmacists who work with children. Writ...
Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission.
Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols...
Cheney, J. L. Saddington, H. Shevill, E. Wainwright, C. E. Alpern, A. N. Quittner, A. L.
Early diagnosis and treatment of lower respiratory tract infections, particularly those with Pseudomonas aeruginosa, are the mainstay of management of lung disease in cystic fibrosis. When sputum samples are unavailable, treatment relies mainly on cultures from oropharyngeal specimens; however, there are concerns regarding the sensitivity of these...
Burkholderia cepacia complex organisms are important transmissible pathogens found in cystic fibrosis (CF) patients. In recent years, the rates
of cross-infection of epidemic strains have declined due to effective infection control efforts. However, cases of sporadic
B. cepacia complex infection continue to occur in some centers. The acquisition pa...
Pseudomonas aeruginosa (PA) is typically an opportunistic pathogen. Many PA infections are facilitated by mechanisms also used in the environment, but infections in the airways of cystic fibrosis (CF) patients can persist for many years, allowing time for the bacteria to adapt to the host. To study this adaptation process we have used Illumina HiSe...
Pseudomonas aeruginosa is the leading cause of
morbidity and mortality in cystic fibrosis (CF). This study
examines the role of organism-specific factors in the pathogenesis
of very early P. aeruginosa infection in the CF airway. A
total of 168 longitudinally collected P. aeruginosa isolates from
children diagnosed with CF following newborn screeni...
Abstract
Rationale: Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has been shown to improve lung function, pulmonary exacerbation rate, respiratory symptoms, and weight gain compared to placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation. Objectives: This randomi...
Shared strains of Pseudomonas aeruginosa are now well recognised in people with cystic fibrosis (CF) and suitable P. aeruginosa laboratory typing tools are pivotal to understanding their clinical significance and guiding infection control policies in CF clinics. We therefore compared a single nucleotide polymorphism (SNP)-based typing method using...
ICT use in cystic fibrosis management provides an alternative means of information supply to individuals, families, health care professionals and other stakeholders. The purpose of this paper is to present the evolution of a series of projects culminating in a project that translates the previous research into practice. In this paper the sequential...
Background
Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with gro...
Aim To review competency evaluations of pharmacists working with children to determine strengths and weaknesses in practice and identify priority areas for professional development.
Methods Competency evaluations were undertaken using an Australian adaptation of the “General Level Framework” (GLF).1 The format of this tool included 102 individual c...
Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In Australia, there is only limited evidence of unrelated patients sharing indistinguishable P. aeruginosa strains. We therefore examined the point-prevalence, distribution, diversity...
Pseudomonas aeruginosa (PA) is an opportunistic pathogen of a wide variety of host organisms, including humans. In the lungs of cystic fibrosis (CF) patients PA infections can persist for many years, during which time the bacteria adapts to the host. Acquired antibiotic resistance is a key feature in the development of chronic PA infection in CF. I...
Rationale:
Denufosol stimulates chloride secretion independent of the chloride channel which is dysfunctional in cystic fibrosis (CF) and therefore has the potential to benefit CF patients regardless of genotype.
Objectives:
To assess the efficacy of denufosol in CF patients with mild lung function impairment age 5 years and older.
Methods:
Th...
Barcoded amplicon sequencing is rapidly becoming a standard method for profiling microbial communities, including the human respiratory microbiome. While this approach has less bias than standard cultivation, several steps can introduce variation including the type of DNA extraction method used. Here we assessed five different extraction methods on...
Clin Microbiol Infect ABSTRACT: Studies of the type 3 secretion system (T3SS) in Pseudomonas aeruginosa isolates from chronically infected older children and adults with cystic fibrosis (CF) show a predominantly exoS+/exoU- (exoS+) genotype and loss of T3SS effector secretion over time. Relatively little is known about the role of the T3SS in the p...
Progressive lung disease accounts for the majority of morbidity and mortality observed in cystic fibrosis (CF). Beyond secondhand smoke exposure and socio-economic status, the effect of specific environmental factors on CF lung function is largely unknown.
Multivariate regression was used to assess correlation between specific environmental factors...
Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis.
We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-C...
An increase in the incidence of empyema worldwide could be related to invasive pneumococcal disease caused by emergent nonvaccine replacement serotypes. To determine bacterial pathogens and pneumococcal serotypes that cause empyema in children in Australia, we conducted a 2-year study of 174 children with empyema. Blood and pleural fluid samples we...
Pseudomonas aeruginosa is an opportunistic pathogen of a wide variety of host organisms, including humans. A niche in which P. aeruginosa is a particularly successful pathogen is in the lungs of cystic fibrosis (CF) patients. These infections can persist for many years, during which time the bacteria adapts to the host.
In order to identify genet...
National surveillance of invasive pneumococcal disease (IPD) includes serotyping Streptococcus pneumoniae (SP) isolates from sterile site cultures. PCR is more sensitive and can identify more SP serotypes (STs) in culture-negative samples. The aim of this study was to determine whether enhanced surveillance of childhood empyema, using PCR, provides...
Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking.
To dete...
Previous aztreonam for inhalation solution (AZLI) studies included patients with cystic fibrosis, Pseudomonas aeruginosa (PA) airway infection, and forced expiratory volume in 1s (FEV(1)) 25% to 75% predicted. This double-blind, multicenter, randomized, placebo-controlled trial enrolled patients (≥6 years) with FEV(1)>75% predicted.
AZLI 75 mg (n=7...
Empyema is a complication of pneumonia, commonly caused by Streptococcus pneumoniae.
To validate the utility of an immunochromatographic test for the detection of S. pneumoniae antigen in the pleural fluid of children with empyema.
Empyema patients had blood and pleural fluid cultured, and polymerase chain reaction (PCR) to detect the S. pneumoniae...
The relationship between viral bronchiolitis in early infancy and subsequent wheezing and asthma has been well established. The aim of the present cross-sectional study was to test the hypothesis that pneumonia severe enough to require hospitalization during the first 2 years of life could also be associated with asthma or asthma-like symptoms in p...
