ORCID Profile
0000-0003-2917-2773
Current Organisations
Northumbria University
,
Murdoch Childrens Research Institute
,
Royal Childrens Hospital
,
University of Melbourne
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Publisher: Wiley
Date: 04-2009
DOI: 10.1002/PPUL.20991
Abstract: Endobronchial ultrasound (EBUS) is a recently introduced technique that has significantly advanced bronchoscopic techniques in adult medicine. Use of ultrasound allows far more accurate localization and s ling of both peripheral pulmonary, as well as mediastinal and hilar lesions. This has led to greater diagnostic success, with a reduced rate of complications. Its performance characteristics in adult populations are equivalent to surgical procedures previously considered gold standard, but it has dramatically reduced morbidity and mortality among patients requiring invasive diagnostic procedures, when compared to surgical approaches. We describe the types of EBUS in clinical use, the method of use, the clinical indications for each procedure, and the potential role for EBUS in pediatric pulmonology. Radial probe EBUS is used in the investigation of peripheral lung lesions and could be adopted in children to achieve accurate biopsy of such lesions. Linear probe EBUS allows minimally invasive biopsy of mediastinal and hilar lesions. It has potentially greater performance characteristics than current biopsy techniques, with no significant complications reported to date. It may be useful in the diagnosis of lymphoma, or neurogenic tumors, as well as many other diseases resulting in mediastinal or hilar lymphadenopathy. EBUS is a minimally invasive technique that allows tissue s ling of peripheral lung lesions, or mediastinal/hilar masses, with a high diagnostic accuracy, and a significantly lower morbidity and mortality than alternative approaches. The indications for and the use of EBUS in pediatric patients is certain to increase in the future.
Publisher: Wiley
Date: 02-09-2021
DOI: 10.1002/PPUL.25642
Abstract: There are limited data in pediatric populations evaluating whether chronic cardiorespiratory conditions are associated with increased risk of coronavirus disease 2019 (COVID‐19). We aimed to compare the rates of chronic cardiac and respiratory disease in children testing positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2[+]) compared with those testing negative (SARS‐CoV‐2[−]) at our institution. Prospective cohort with nested case–control study of all children tested by polymerase chain reaction (PCR) for SARS‐CoV‐2 by nasopharyngeal/oropharyngeal s ling between March and October 2020. Children were identified prospectively via laboratory notification with age and sex‐matching of SARS‐CoV‐2[+] to SARS‐CoV‐2[−] (1:2). Clinical data were extracted from the electronic medical record. In total, 179 SARS‐CoV‐2[+] children (44% females, median age 3.5 years, range: 0.1–19.0 years) were matched to 391 SARS‐CoV‐2[−] children (42% female, median age 3.7 years, range: 0.1–18.3 years). The commonest comorbidities showed similar frequencies in the SARS‐CoV‐2[+] and [−] groups: asthma ( n = 9, 5% vs. n = 17, 4.4%, p = 0.71), congenital heart disease ( n = 6, 3.4% vs. n = 7, 1.8%, p = 0.25) and obstructive sleep apnoea ( n = 4, 2.2% vs. n = 10, 2.3%, p = 0.82). In the SARS‐CoV‐2[+] group, the prevalence of symptomatic disease was similar among children with and without cardiorespiratory comorbidities ( n = 12, 75% vs. n = 103, 57%, p = 0.35). A high proportion of children hospitalized with SARS‐CoV‐2 infection had cardiac comorbidities (23.8%). In this single site data set, rates of pre‐existing cardiorespiratory disease were similar in SARS‐CoV‐2[+] and SARS‐CoV‐2[−] children. Rates of symptomatic infection were similar between children with and without cardiorespiratory comorbidity. High rates of comorbid cardiac disease were observed among hospitalized children with COVID‐19 warranting further research to inform vaccine prioritization.
Publisher: Wiley
Date: 03-06-2021
DOI: 10.1111/JPC.15601
Abstract: To describe the epidemiology of respiratory viruses in children before and during the 2020 SARS‐CoV‐2 pandemic and the relationship to public health measures instituted by the Victorian government. Retrospective audit of respiratory viruses at a tertiary paediatric hospital in Melbourne from January 2015 up to week 47, 2020 in children under 18 years of age. The proportion of positive cases in weeks 1–47 in 2015–2019 (period 1) were compared to weeks 1–47, 2020 (period 2), and reviewed in the context of public health restrictions in Victoria. An annual average of 4636 tests were performed in period 1 compared to 3659 tests in period 2. Proportions of positive influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human parainfluenza virus were significantly reduced in period 2 compared to period 1: 77.3, 89.4, 68.6 and 66.9% reductions, respectively (all P 0.001). From week 12–47, 2020, 28 893 SARS‐CoV‐2 tests were performed with a 0.64% positivity rate. Influenza viruses were not detected after week 17, RSV was not detected after week 35. Strict public health measures and border closures were successful in eliminating community transmission of SARS‐CoV‐2 in Melbourne. This was associated with a significant reduction in other respiratory virus infections in children. Identifying sustainable and effective ongoing public health interventions to reduce transmission of RSV and influenza could result in reduced morbidity and mortality in children and requires further research.
Publisher: Informa UK Limited
Date: 05-06-2017
DOI: 10.1080/17476348.2017.1335197
Abstract: The prevalence and awareness of bronchiectasis not related to cystic fibrosis (CF) is increasing and it is now recognized as a major cause of respiratory morbidity, mortality and healthcare utilization worldwide. The need to elucidate the early origins of bronchiectasis is increasingly appreciated and has been identified as an important research priority. Current treatments for pediatric bronchiectasis are limited to antimicrobials, airway clearance techniques and vaccination. Several new drugs targeting airway inflammation are currently in development. Areas covered: Current management of pediatric bronchiectasis, including discussion on therapeutics, non-pharmacological interventions and preventative and surveillance strategies are covered in this review. We describe selected adult and pediatric data on bronchiectasis treatments and briefly discuss emerging therapeutics in the field. Expert commentary: Despite the burden of disease, the number of studies evaluating potential treatments for bronchiectasis in children is extremely low and substantially disproportionate to that for CF. Research into the interactions between early life respiratory tract infections and the developing immune system in children is likely to reveal risk factors for bronchiectasis development and inform future preventative and therapeutic strategies. Tailoring interventions to childhood bronchiectasis is imperative to halt the disease in its origins and improve adult outcomes.
Publisher: European Respiratory Society
Date: 09-2015
Publisher: Wiley
Date: 21-05-2022
DOI: 10.5694/MJA2.51542
Publisher: Oxford University Press (OUP)
Date: 18-04-2014
DOI: 10.1093/CID/CIU225
Publisher: Wiley
Date: 11-2017
Publisher: Springer Science and Business Media LLC
Date: 29-06-2018
Publisher: European Respiratory Society
Date: 07-09-2020
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: BMJ
Date: 05-2022
DOI: 10.1136/BMJRESP-2022-001236
Abstract: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance. We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance. Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians. ACTRN12619000564156.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.RMED.2021.106547
Abstract: There is a current lack of consensus amongst paediatric radiologists and respiratory paediatricians as to the correct CT definition of bronchiectasis in children. Using contemporary low-dose CT, our objectives were to determine the upper limit of normal for broncho-arterial ratio (BAR) in children and to evaluate the effect of age and general anaesthesia. Measurements of 330 broncho-arterial ratios from 51 children (0-19 years) undergoing low-dose CT chest for non-respiratory indications were performed by 3 blinded observers (two radiologists, one respiratory physician) using four different methods. Inter-observer reliability, mean BAR and reference ranges (mean±2SD) were calculated. Correlation between age and BARs were examined. Mean BAR for CT under general anaesthesia and CT awake were compared. Inter-observer correlation was extremely high for all measurements (0.93-0.97). There was a weak positive correlation between age and BAR in the CT-awake group (r = 0.33, 95%CI: 0.03-0.57 p = 0.031) using the inner-bronchial wall to artery, short-axis measurement. CT under general anaesthesia showed significantly higher BAR compared to CT-awake [mean difference 0.13 (95%CI: 0.05-0.22 p = 0.004)]. For the CT-awake group, the mean BAR was 0.65 (range: 0.42 to 0.89), with no child having a BAR above 0.9. Using a standardised approach, we have shown that a broncho-arterial ratio above 0.9 in children undergoing awake CT is abnormal and suggests airway widening or radiological bronchiectasis. Children undergoing CT under anaesthesia have higher BARs than those undergoing awake CT. A weak positive correlation between broncho-arterial ratio and age was observed, hence, age-adjusted cut-offs for BAR warrant further study.
Publisher: Wiley
Date: 25-10-2021
DOI: 10.1111/JPC.15811
Abstract: The global disruption of the COVID‐19 pandemic has impacted the life of every child either directly or indirectly. This review explores the pathophysiology, immune response, clinical presentation and treatment of COVID‐19 in children, summarising the most up‐to‐date data including recent developments regarding variants of concern. The acute infection with SARS‐CoV‐2 is generally mild in children, whilst the post‐infectious manifestations, including paediatric inflammatory multisystem syndrome temporally associated with SARS‐CoV‐2 (PIMS‐TS) and ‘long COVID’ in children, are more complex. Given that most research on COVID‐19 has focused on adult cohorts and that clinical manifestations, treatment availability and impacts differ markedly in children, research that specifically examines COVID‐19 in children needs to be prioritised.
Publisher: Elsevier BV
Date: 11-2016
Publisher: Wiley
Date: 15-06-2011
Publisher: MDPI AG
Date: 27-04-2023
Abstract: Tachypnoea in the newborn is common. It may arise from the many causes of the respiratory distress syndrome such as hyaline membrane disease, transient tachypnoea of the newborn, meconium aspiration etc. Congenital heart disease rarely presents with early tachypnoea on day one or two, in contrast to the early presentation of cyanosis, unless there is “pump” (ventricular) failure such as may occur in a cardiomyopathy/myocarditis, or as a result of severe obstruction to either ventricle. Space-occupying lesions within the chest, for ex le from a diaphragmatic hernia or a congenital cystic adenomatoid malformation, may present with early tachypnoea, as can a metabolic cause resulting in acidosis. The aim of this paper, however, is to focus on infants where the tachypnoea persists or develops beyond the newborn period, at times with minimal signs but occasionally with serious underlying pathology. They include causes that may have originated in the newborn but then persist for ex le, arising from pulmonary hypoplasia or polycythemia. Many congenital cardiac abnormalities, particularly those causing left sided obstructive lesions, or those due to an increasing left to right shunt from large communications between the systemic and pulmonary circulations, need be considered. Respiratory causes, for ex le arising from aspiration, primary ciliary dyskinesia, cystic fibrosis, or interstitial lung disease, may lead to ongoing tachypnoea. Infective causes such as bronchiolitis or infantile wheeze generally are readily recognisable. Finally, there are a few infants who present with persistent tachypnoea over the first few weeks/months of their life who remain well and have normal investigations with the tachypnoea gradually resolving. How should one approach infants with persistent tachypnoea?
Publisher: BMJ
Date: 21-06-2021
DOI: 10.1136/ARCHDISCHILD-2021-321795
Abstract: To explore parent perspectives on accessing mental healthcare for children with a chronic physical health condition. Qualitative research using semistructured interviews and Framework Analysis. Rankings were used to select attributes for a Discrete Choice Experiment (DCE). Four specialty outpatient clinics (diabetes, epilepsy, bronchiectasis unrelated to cystic fibrosis and epidermolysis bullosa) at an Australian tertiary paediatric hospital. Eighteen parents of children with a chronical physical health condition. Most parents identified the child’s general practitioner and/or hospital team as an initial pathway to seek help if they were worried about their child’s mental health. Parents see mental healthcare as part of care for the whole child and want the outpatient clinics to proactively discuss child and family mental health, as well as refer to appropriate services as needed. The hospital being a familiar, child-friendly environment was identified as a key reason the hospital might be a desired place to access mental healthcare, as previous research has found. Six attributes of mental health services were identified as important and will be included in an upcoming DCE: travel time, cost, wait time, available hours, knowledge of physical health condition, and recommendation. This study highlights the opportunity presented in specialist outpatient clinics to address the often unmet mental healthcare needs of children with chronic physical health conditions. Parents identified practical ways for outpatient clinics to better facilitate access to mental healthcare. These will be further explored through a quantitative study of parent preferences.
Publisher: Elsevier BV
Date: 2022
DOI: 10.2139/SSRN.4011896
Publisher: Wiley
Date: 07-02-2023
DOI: 10.1111/ALL.15662
Abstract: Preterm birth is associated with aberrant pulmonary development and increased susceptibility to a range of chronic lung diseases. Even in healthy preterms, the prevalence of physician‐diagnosed asthma is far higher than in infants born at term. While physiological, environmental, and genetic factors have been studied extensively, few studies have investigated the immunological factors underpinning this increased susceptibility. Lower rates of atopy and allergic sensitization in preterm compared to term infants suggests non‐allergic mechanisms may be driving asthma development in preterms. Preterm infants are more likely to develop severe RSV and HRV disease and have altered microbiomes compared to term infants. Therefore, investigating the differences in immunological interactions (e.g., response to viral infections, microbiome) between children born preterm and term will aid in understanding the immunological basis for their increased susceptibility to asthma development. This is critical to inform the development of interventions to reduce the burden of asthma in this highly vulnerable demographic.
Publisher: Public Library of Science (PLoS)
Date: 08-05-2015
Publisher: Informa UK Limited
Date: 27-08-2019
Publisher: Wiley
Date: 07-10-2014
DOI: 10.1002/PPUL.22858
Abstract: Disc battery ingestion in children is becoming increasingly common with the proliferation of small battery-powered electronic devices. In the case of esophageal impaction, the likelihood and severity of complications are proportionate to the time between ingestion and removal. Tracheo-esophageal fistulae (TOF) are a recognized complication and can be life-threatening. We describe an interesting case of disc battery ingestion with delayed recognition of a TOF. We document the tracheal mucosal healing process of a large airway defect and describe the role of bronchoscopy in guiding the timing of surgical intervention. This case highlights the important role of early bronchoscopic assessment in management of these patients.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Wiley
Date: 07-2021
DOI: 10.1111/JPC.15585
Publisher: Elsevier BV
Date: 04-2017
Publisher: Wiley
Date: 16-05-2020
DOI: 10.1111/JPC.14491
Abstract: To describe the epidemiology and treatment of respiratory syncytial virus (RSV) infection in a tertiary paediatric intensive care unit (PICU), including the clinical presentations, comorbidities, respiratory support required, costs and outcomes. This study was an analysis of a database for all children with RSV infections admitted to the PICU in Melbourne between 2005 and 2015. A total of 604 episodes of community-acquired RSV infections were analysed, and the median age of children was 4 months (interquartile range 2-14 months) 94% of cases had lower respiratory tract infection, principally bronchiolitis, and 8.9% presented with extrapulmonary features. Respiratory support included humidified high-flow nasal cannula oxygen therapy (76% of patients since its introduction in 2011), non-invasive ventilation (41%) and intubation and mechanical ventilation (32%). Almost half (n = 270 45%) had one or more pre-existing comorbid condition. Risk factors for intubation and mechanical ventilation were presence of comorbidities (odds ratio 1.97 confidence interval 1.39-2.79, P < 0.001) and transfer from an external hospital (odds ratio 1.82 confidence interval 1.58-2.57, P < 0.001). Of the children without pre-existing comorbidities, 25% required intubation and mechanical ventilation. Following the introduction of humidified high-flow nasal cannula oxygen therapy, the number of annual PICU admissions for RSV infection doubled however, the number of children requiring intubation remained unchanged. The median length of intensive care unit stay was 3.7 days and further hospital stay was 3.6 days, and the average cost per case was approximately AU$20000. RSV infection carries a high burden in PICU, in bed-days and cost. Chronic comorbidities and transfer from a peripheral hospital were associated with a higher rate of need for mechanical ventilation.
Publisher: Wiley
Date: 08-09-2022
DOI: 10.1111/JPC.16197
Abstract: Globally, respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in young children, and the association between severe RSV disease and later recurrent wheeze and asthma is well established. Whilst a causal link between RSV and wheeze/asthma is not yet proven, immunological evidence suggests skewing towards a Th2-type response, and d ening of IFN-γ antiviral immunity during RSV infection underpins airway hyper-reactivity in a subset of susceptible children after RSV infection. Age at primary RSV infection, viral co-infection and genetic influences may act as effect-modifiers. Despite the significant morbidity and mortality burden of RSV disease in children, there is currently no licensed vaccine. Recent advancements in RSV preventatives, including long-acting monoclonal antibodies and maternal vaccinations, show significant promise and we are on the cusp of a new era in RSV prevention. However, the potential impact of RSV preventatives on subsequent wheeze and asthma remains unclear. The ongoing COVID-19 pandemic and associated public health measures have disrupted the usual seasonality of RSV. Whilst this has posed challenges for health-care services it has also enhanced our understanding of RSV transmission. The near absence of RSV cases during the first year of the pandemic in the context of strict public health measures has provided a rare opportunity to study the impact of delayed age of primary RSV infection on asthma prevalence. In this review, we summarise current understanding of the association between RSV, recurrent wheeze and asthma with a focus on pathophysiology, preventative strategies and future research priorities.
Publisher: Wiley
Date: 29-10-2020
DOI: 10.1111/AJO.13270
Publisher: Elsevier BV
Date: 12-2022
Publisher: Frontiers Media SA
Date: 30-09-2020
Publisher: Frontiers Media SA
Date: 13-02-2015
Publisher: Wiley
Date: 12-10-2021
DOI: 10.1111/RESP.13950
Publisher: Wiley
Date: 20-06-2014
DOI: 10.1002/PPUL.22792
Abstract: Wet cough is a common feature of many disease processes affecting children. Our aim was to examine the relationships between cough nature, lower airway infection (bacterial, viral, and viral-bacterial) and severity of neutrophilic airway inflammation. We hypothesized that viral-bacterial co-infection of the lower airway would be associated with wet cough and heightened neutrophilic airway inflammation. We prospectively recruited 232 children undergoing elective flexible bronchoscopy. Participants were grouped using a cough nature symptom-based approach, into wet, dry or no cough groups. Broncho-alveolar lavage (BAL) and clinical data, including presence, nature, and duration of cough and key demographic factors, were collected. Children with wet cough (n = 143) were more likely to have lower airway bacterial infection (OR 2.6, P = 0.001), viral infection (OR 2.04, P = 0.045) and viral-bacterial co-infection (OR 2.65, P = 0.042) compared to those without wet cough. Wet cough was associated with heightened airway neutrophilia (median 19%) as compared to dry or no cough. Viral-bacterial co-infection was associated with the highest median %neutrophils (33.5%) compared to bacteria only, virus/es only and no infection (20%, 18%, and 6%, respectively, P < 0.0001). Children with wet cough had higher rates of lower airway infection with bacteria and viruses. Maximal neutrophilic airway inflammation was seen in those with viral-bacterial co-infection. Cough nature may be a useful indicator of infection and inflammation of the lower airways in children.
Publisher: CSIRO Publishing
Date: 04-10-2022
DOI: 10.1071/AH22075
Abstract: Objectives To identify features of mental health services that affect the uptake of services among parents of children with chronic medical conditions, to inform the design of pathways into mental health care. Methods A discrete choice experiment in which participants made choices between hypothetical mental health services described in terms of service features: cost, wait time, provider knowledge of chronic medical conditions, recommendations, opening hours, and travel time. Participants were parents of children attending The Royal Children’s Hospital outpatient clinics for the management of a chronic medical condition who completed the online survey between August 2020 and January 2021. The uptake of mental health services with differing features was predicted based on regression models examining the relationship between choice and service features, and accounting for participant characteristics and unobserved heterogeneity. Results The s le comprised 112 parents, of whom 52% reported unmet needs. The most influential service features were wait times, cost, recommendation from medical specialists, and mental health provider knowledge of chronic medical conditions. Predicted uptake of a realistic service showed inequalities across income, parental education, and single parent status. A service comprising preferred features was predicted to eliminate these inequalities. Conclusions Reducing cost and wait time for mental health services could reduce unmet need among children with chronic medical conditions. Specific approaches to tackle the high levels of unmet needs in this group include equipping medical specialists to recommend mental health providers and training mental health providers on the impacts of chronic medical conditions on children. Offering preferred services could increase uptake and reduce inequalities in mental health care.
Publisher: Wiley
Date: 25-10-2021
DOI: 10.1111/JPC.15786
Abstract: Victoria experienced two ‘waves’ of COVID‐19 between March and September 2020 and more cases than any other jurisdiction in Australia. Although world‐wide reports of COVID‐19 reflect that children are less likely to experience severe disease compared with adults, hospitalisations and deaths have been reported. We report testing and outcomes of children with SARS‐CoV‐2 infection presenting to a tertiary paediatric hospital in Melbourne. We conducted a prospective cohort study at The Royal Children's Hospital (RCH), including all children and adolescents (aged 0–18 years) who presented and were tested for SARS‐CoV‐2 over a 6‐month period, between 21 March 2020, up to the 21 September 2020. Detailed epidemiological and clinical data were recorded. A total of 19 708 tests for SARS‐CoV‐2 were performed in 14 419 patients. One hundred and eighty patients tested positive for SARS‐CoV‐2 (1.2%). 110 (61%) were symptomatic, 60 (33%) were asymptomatic and 10 (6%) were pre‐symptomatic. Close contacts of a positive case were associated with a higher risk of a testing positive for SARS‐CoV‐2 (120/2027 (6%) vs. 60/14589 (0.4%), RD 5.5 (95% CI 4.5 to 6.5), P 0.001). Eighteen (10%) SARS‐CoV‐2‐positive patients were admitted to hospital with one patient requiring intensive care. All patients recovered fully with no deaths. In Victorian children presenting to a tertiary hospital, SARS‐CoV‐2 infection caused predominantly mild or asymptomatic infection, with most children not requiring hospitalisation.
Publisher: Elsevier BV
Date: 12-2013
Publisher: Elsevier BV
Date: 06-2021
Publisher: BMJ
Date: 15-09-2021
DOI: 10.1136/ARCHDISCHILD-2021-322435
Abstract: Early recognition of children at risk of severe respiratory syncytial virus (RSV) lower respiratory tract infection is important as it informs management decisions. We aimed to evaluate factors associated with severe disease among young children hospitalised with RSV infection. We conducted a retrospective cohort study of all children years of age hospitalised for RSV lower respiratory tract infection at a single tertiary paediatric hospital over three RSV seasons (January 2017–December 2019). We classified children as having ‘moderate’ or ‘severe’ disease based on the level of respiratory intervention and used univariable and multivariable regression models to determine factors associated with severe disease. Of 970 hospitalised children, 386 (40%) were classified as having ‘severe’ and 584 (60%) as having ‘moderate’ RSV disease. On multivariable analyses, age months (OR: 2.3, 95% CI 1.6 to 3.3, p .0001), prematurity (OR: 1.6, 95% CI 1.1 to 2.4, p=0.02) and RSV–parainfluenza virus type 3 (PIV3) codetection (OR: 2.6, 95% CI 1.05 to 6.5, p=0.04) were independently associated with severe disease. Younger age, prematurity and PIV3 codetection were associated with severe RSV disease in children years of age hospitalised with RSV infection. The association between PIV3 and severe RSV disease is a novel finding and warrants further investigation.
Publisher: Wiley
Date: 06-2021
DOI: 10.1002/PED4.12262
Abstract: Maternal urogenital human papillomavirus (HPV) infection may place neonates at risk of HPV acquisition and subsequently lower respiratory infections as HPV can influence development of immunity. The respiratory HPV prevalence is not known in remote‐dwelling Aboriginal infants, who are at high risk of respiratory infection and where the population prevalence of urogenital HPV in women is high. These data are necessary to inform HPV vaccination regimens. A retrospective analysis using PCR specific for HPV was performed on 64 stored nasopharyngeal swabs from remote‐dwelling Aboriginal infants 6 months of age, with and without hospitalised pneumonia. HPV DNA was not detected in any specimen. Despite the negative result, we cannot exclude a role for HPV in respiratory infections affecting infants in this population however, our data do not support HPV as an important contributor to acute respiratory infection in remote‐dwelling Aboriginal children.
Publisher: Springer Science and Business Media LLC
Date: 15-11-2021
DOI: 10.1038/S43856-021-00047-7
Abstract: Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups.
Publisher: European Respiratory Society (ERS)
Date: 07-2022
Publisher: Oxford University Press (OUP)
Date: 18-03-2021
DOI: 10.1093/CID/CIAB240
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.JCF.2011.08.005
Abstract: To evaluate changes in prevalence of an epidemic strain of Pseudomonas aeruginosa (AES-1, Australian epidemic strain, type 1) in a paediatric cystic fibrosis (CF) centre practising cohort segregation, to describe the patients' clinical characteristics at acquisition and observe mortality rates. Cohort segregation was introduced in our paediatric CF clinic January 2000. The prevalence of AES-1 was analysed in 1999, 2002 and 2007. Age at acquisition, lung function, presence of bronchiectasis, hospitalisations, prior P. aeruginosa infection and mortality rates were collected. AES-1 infection was determined by pulse-field-gel-electrophoresis (PFGE) on airway specimen cultures taken three monthly. The prevalence of AES-1 declined from 21% in 1999 to 14% in 2002 (risk difference 7% (95% CI 1,13) p=0.0256) and to 6% in 2007 (risk difference 8% (95% CI 3,13) p=0.0018). New acquisitions after the introduction of cohort segregation were uncommon (10 by 2002 and another 7 by 2007) with a declining incidence of 3.3 cases/year (1999 to 2002) compared to 1.4 cases/year (2002 to 2007). Twenty-two of 32 (69%) deaths between 1999 and 2007 occurred in patients infected with AES-1. Cohort segregation has been associated with reductions in the prevalence of AES-1 in our CF clinic. Mortality was higher in patients infected with AES-1 than other organisms.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.JCF.2021.11.005
Abstract: There is no data exclusively on the relationship between health-related quality-of-life (HRQOL) and lung disease severity in early school-aged children with cystic fibrosis (CF). Using data from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) we assessed the relationships between HRQOL, lung function and structure. 125 children aged 6.5-10 years enrolled in the AREST CF program were included from CF clinics at Royal Children's Hospital (RCH), Melbourne (n = 66) and Perth Children's Hospital (PCH), Perth (n = 59), Australia. Demographics, HRQOL measured by Cystic Fibrosis Questionnaire-Revised (CFQ-R), spirometry, multiple-breath washout (MBW) and chest CT were collected across two years. Correlation between CFQ-R scores and lung structure/function parameters and agreement between parent-proxy and child-reported HRQOL were evaluated. No correlation was observed between most CFQ-R domain scores and FEV1 z-scores, excepting weak-positive correlation with parent CFQ-R Physical (rho = 0.21, CI 0.02-0.37), and Weight (rho = 0.21, CI 0.03-0.38) domain and child Body domain (rho = 0.26, CI 0.00-0.48). No correlation between most CFQ-R domain scores and LCI values was noted excepting weak-negative correlation with parent Respiratory (rho = -0.23, CI HRQOL correlated poorly with lung function and structure in early school-aged children with CF, hence clinical trials should consider these outcomes independently when determining study end-points.
Publisher: European Respiratory Society
Date: 15-09-2018
Publisher: Wiley
Date: 13-10-2021
DOI: 10.1111/JPC.15791
Abstract: Children globally have been profoundly impacted by the coronavirus disease 2019 (COVID‐19) pandemic. This review explores the direct and indirect public health impacts of COVID‐19 on children. We discuss in detail the transmission dynamics, vaccination strategies and, importantly, the ‘shadow pandemic’, encompassing underappreciated indirect impacts of the pandemic on children. The indirect effects of COVID‐19 will have a long‐term impact beyond the immediate pandemic period. These include the mental health and wellbeing risks, disruption to family income and attendant stressors including increased family violence, delayed medical attention and the critical issue of prolonged loss of face‐to‐face learning in a normal school environment. Amplification of existing inequities and creation of new disadvantage are likely additional sequelae, with children from vulnerable families disproportionately affected. We emphasise the responsibility of paediatricians to advocate on behalf of this vulnerable group to ensure the longer‐term effects of COVID‐19 public health responses on the health and wellbeing of children are fully considered.
Publisher: Wiley
Date: 02-2022
DOI: 10.1111/IMJ.15510
Abstract: The COVID‐19 pandemic has generated significant debate about how emerging infections can be treated in the absence of evidence‐based therapies to combat disease. In particular, the use of off‐label therapies outside of a clinical trial setting has been controversial. To longitudinally study policies and prescribing practices pertaining to therapies for COVID‐19 in Australian health services during 2020. Prospective data were collected from participating Australian health services who may care for patients with COVID‐19 via an electronic portal. A single informant from each health service was emailed a survey link at regular intervals. Information was sought regarding changes to COVID‐19 policy at their service and use of therapies for COVID‐19. Overall, 78 hospitals were represented from 39 respondents with longitudinal data collection from May to December 2020. All Australian states/territories were represented with the majority (34/39 87%) of respondents located in a major city. Just over half (20/39) of respondents had a written policy for COVID‐19 therapy use at their health service at survey enrolment and policies changed frequently throughout the pandemic. Therapy use outside of a clinical trial was reported in 54% of health services, most frequently in Victoria, correlating with higher numbers of COVID‐19 cases. At study commencement, hydroxychloroquine was most frequently used, with corticosteroids and remdesivir use increasingly throughout the study period. Our results reflect the reactive nature of prescribing of therapies for COVID‐19 and highlight the importance of evidence‐based guidelines to assist prescribers.
Publisher: Wiley
Date: 23-10-2017
DOI: 10.1111/PCMR.12620
Abstract: A SNP within intron4 of the interferon regulatory factor4 (IRF4) gene, rs12203592*C/T, has been independently associated with pigmentation and age-specific effects on naevus count in European-derived populations. We have characterized the cis-regulatory activity of this intronic region and using human foreskin-derived melanoblast strains, we have explored the correlation between IRF4 rs12203592 homozygous C/C and T/T genotypes with TYR enzyme activity, supporting its association with pigmentation traits. Further, higher IRF4 protein levels directed by the rs12203592*C allele were associated with increased basal proliferation but decreased cell viability following UVR, an etiological factor in melanoma development. Since UVR, and accompanying IFNγ-mediated inflammatory response, is associated with melanomagenesis, we evaluated its effects in the context of IRF4 status. Manipulation of IRF4 levels followed by IFNγ treatment revealed a subset of chemokines and immuno-evasive molecules that are sensitive to IRF4 expression level and genotype including CTLA4 and PD-L1.
Publisher: John Wiley & Sons, Ltd
Date: 08-09-2010
Publisher: Elsevier BV
Date: 05-2022
Publisher: BMJ
Date: 11-2021
DOI: 10.1136/BMJOPEN-2021-054510
Abstract: To present Australia-wide data on paediatric COVID-19 and multisystem inflammatory syndromes to inform health service provision and vaccination prioritisation. Prospective, multicentre cohort study. Eight tertiary paediatric hospitals across six Australian states and territories in an established research surveillance network—Paediatric Active Enhanced Disease (PAEDS). All children aged years with SARS-CoV-2 infection including COVID-19, Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) and Kawasaki-like disease TS infection (KD-TS) treated at a PAEDS site from 24 March 2020 to 31 December 2020. Laboratory-confirmed SARS-CoV-2 infection. Incidence of severe disease among children with COVID-19, PIMS-TS and KD-TS. We also compared KD epidemiology before and during the COVID-19 pandemic. Among 386 children with SARS-CoV-2 infection, 381 (98.7%) had COVID-19 (median 6.3 years (IQR 2.1–12.8),53.3% male) and 5 (1.3%) had multisystem inflammatory syndromes (PIMS-TS, n=4 KD-TS, n=1) (median 7.9 years (IQR 7.8–9.8)). Most children with COVID-19 (n=278 73%) were Australian-born from jurisdictions with highest community transmission. Comorbidities were present in 72 (18.9%) cardiac and respiratory comorbidities were most common (n=32/72 %). 37 (9.7%) children with COVID-19 were hospitalised, and two (0.5%) required intensive care. Postinfective inflammatory syndromes (PIMS-TS/KD-TS) were uncommon (n=5 1.3%), all were hospitalised and three (3/5 60%) required intensive care management. All children recovered and there were no deaths. KD incidence remained stable during the pandemic compared with prepandemic. Most children with COVID-19 had mild disease. Severe disease was less frequent than reported in high prevalence settings. Preventative strategies, such as vaccination, including children and adolescents, could reduce both the acute and postinfective manifestations of the disease.
Publisher: Wiley
Date: 12-2016
DOI: 10.1111/JPC.13413
Publisher: Wiley
Date: 21-04-2022
DOI: 10.5694/MJA2.51510
Publisher: BMJ
Date: 06-2022
DOI: 10.1136/BMJRESP-2022-001212
Abstract: Chronic bronchitis in childhood is associated with a diagnosis of asthma and/or bronchiectasis a few years later, however, consequences into middle-age are unknown. To investigate the relationship between childhood bronchitis and respiratory-related health outcomes in middle-age. Cohort study from age 7 to 53 years. General population of European descent from Tasmania, Australia. 3202 participants of the age 53-year follow-up (mean age 53, range 51–55) of the Tasmanian Longitudinal Health Study cohort who were born in 1961 and first investigated at age 7 were included in our analysis. Multivariable linear and logistic regression. The association between parent reported childhood bronchitis up to age 7 and age 53-year lung conditions (n=3202) and lung function (n=2379) were investigated. Among 3202 participants, 47.5% had one or more episodes of childhood bronchitis, classified according to severity based on the number of episodes and duration as: ‘non-recurrent bronchitis’ (28.1%) ‘recurrent non-protracted bronchitis’ (18.1%) and ‘recurrent-protracted bronchitis’ (1.3%). Age 53 prevalence of doctor-diagnosed asthma and pneumonia (p-trend .001) and chronic bronchitis (p-trend=0.07) increased in accordance with childhood bronchitis severities. At age 53, ‘recurrent-protracted bronchitis’ (the most severe subgroup in childhood) was associated with doctor-diagnosed current asthma (OR 4.54, 95% CI 2.31 to 8.91) doctor-diagnosed pneumonia (OR=2.18 (95% CI 1.00 to 4.74)) and, paradoxically, increased transfer factor for carbon monoxide (z-score +0.51 SD (0.15–0.88)), when compared with no childhood bronchitis. In this cohort born in 1961, one or more episodes of childhood bronchitis was a frequent occurrence. ‘Recurrent-protracted bronchitis’, while uncommon, was especially linked to multiple respiratory outcomes almost five decades later, including asthma, pneumonia and raised lung gas transfer. These findings provide insights into the natural history of childhood ‘bronchitis’ into middle-age.
Publisher: Wiley
Date: 24-10-2021
DOI: 10.5694/MJA2.51305
Publisher: Elsevier BV
Date: 06-2014
Publisher: Therapeutic Guidelines Limited
Date: 08-2014
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.JPEDS.2012.03.049
Abstract: To determine bronchoalveolar lavage (BAL) levels of 3 innate immunity components (human β-defensin-2 [hBD2], mannose-binding lectin [MBL], and surfactant protein-A [SP-A]), the relationship with airway neutrophilia and infection, and cytokine production of stimulated BAL cells in children with current protracted bacterial bronchitis (PBB), children with resolved PBB (PBB well), and controls. BAL of 102 children (mean age 2.8 years) fulfilling predefined criteria of current PBB (n = 61), PBB well (n = 20), and controls (n = 21) was cultured (quantitative bacteriology) and viruses examined by polymerase chain reaction. hBD2, MBL, and SP-A were measured, and cytokine production by lipopolysaccharide-stimulated BAL cells was determined. Median hBD2 and MBL levels were significantly higher in the current PBB group (hBD2 = 164.4, IQR 0-435.5 pg/mL MBL = 1.7, 0.4-4 ng/mL) than in the PBB well group (hBD2 = 0, IQR 0-85.2 MBL = 0.6, IQR 0.03-2.9) and controls (hBD2 = 3.6, IQR 0-126 MBL = 0.4, IQR 0.02-79). hBD2 was significantly higher in children with airway infection (n = 54 median 76.9, IQR 0-397.3) compared with those without (n = 48 0, IQR 0-236.3), P= .04. SP-A levels and cytokine production of stimulated BAL cells were similar between groups. In children's airways, hBD2, but not MBL and SP-A, relates to inflammation and infection. In children with PBB, mechanisms involving airway hBD2 and MBL are augmented. These pulmonary innate immunity components and the ability of BAL cells to respond to stimuli are unlikely to be deficient.
Publisher: Wiley
Date: 04-2009
DOI: 10.1002/PPUL.20979
Abstract: Sarcoidosis in children can present with extra-pulmonary manifestations, making diagnosis difficult. We describe a case of sarcoidosis in a child, presenting as a Guillain-Barré-like illness with the incidental finding of a perihilar mass. We also report the first successful use of the minimally invasive technique of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) to delineate the cause of hilar lymphadenopathy in a child.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2022
End Date: 2014
Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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End Date: 2015
Funder: National Health and Medical Research Council
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End Date: 2024
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2020
End Date: 2024
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2012
End Date: 2015
Funder: National Health and Medical Research Council
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