ORCID Profile
0000-0002-4414-7915
Current Organisations
Hospital for Sick Children
,
Royal College of Paediatrics and Child Health
,
University Malaya Medical Centre
,
Royal Belfast Hospital for Sick Children
,
Sydney Children's Hospital Randwick
,
Royal London Hospital
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Publisher: Wiley
Date: 23-11-2017
DOI: 10.1111/JPC.13789
Abstract: Adenotonsillectomy is performed in children with recurrent tonsillitis or obstructive sleep apnoea. Children at risk of post-operative respiratory complications are recommended to be monitored in paediatric intensive care unit (PICU). The aim of the study is to review the risk factors for post-operative complications and admissions to PICU. A review of medical records of children who underwent adenotonsillectomy between January 2011 and December 2014 was performed. Association between demographic variables and post-operative complications were examined using chi-square and Mann-Whitney tests. A total of 214 children were identified, and of these, 19 (8.8%) experienced post-operative complications. Six children (2.8%) had respiratory complications: hypoxaemia in four and laryngospasm requiring reintubation in a further two. Both of the latter patients were extubated upon arrival to PICU and required no escalation of therapy. A total of 13 (6.1%) children had non-respiratory complications: 8 (3.7%) had infection and 5 (2.3%) had haemorrhage. A total of 26 (12.1%) children were electively admitted to PICU and mean stay was 19.5 (SD ± 13) h. No association between demographic characteristics, comorbid conditions or polysomnographic parameters and post-operative complications were noted. A total of 194 (90.7%) children stayed only one night in hospital (median 1 day, range 1-5 days). The previously identified risk factors and criteria for PICU admission need revision, and new recommendations are necessary.
Publisher: Wiley
Date: 31-01-2014
DOI: 10.1002/PPUL.23001
Abstract: To investigate the impact of chronic suppurative lung disease (CSLD) on growth and lung function in the child as well as quality of life of the child and parent. Cross-sectional study in 60 children with CSLD, bronchiectasis (including cystic fibrosis) and bronchiolitis obliterans. Thirty-five parents were interviewed while the remaining patients' data were collated from medical notes. Anthropometric measurements at first diagnosis and at interview were compared. The most recent lung function was also collected. The Parent Cough-Specific Quality of Life (PC-QOL) and the Depression, Anxiety and Stress (DASS21) questionnaires were administered to parents. The median (range) age at diagnosis was 1.3 (0.2-11) years. The median (IQR) duration between anthropometric measurements was 35 (15, 59) months. Children with cystic fibrosis (CF) had improvements both in weight and BMI, whereas children with non-CF CSLD had no improvements in any growth parameter. Seventy-eight percent of children who performed spirometry had values <80% of normal predicted value. PC-QOL scores were low. Frequent exacerbations (more than twice in the past 6 months) and cough (more than 2 days/week) were not associated with significantly lower PC-QOL scores. Seventy-seven percent of interviewed parents had abnormal DASS21 scores with 54% being stressed and 51% being depressed. Mental health was better in parents of children with CF. CSLD had a negative impact on growth, lung function, and quality of life. Children with CF had a better outcome in growth as well as better parental mental health compared to children with other etiologies. Pediatr Pulmonol. 2014 49:435-440. © 2013 Wiley Periodicals, Inc.
Publisher: Wiley
Date: 22-07-2007
DOI: 10.1111/J.1365-2222.2007.02780.X
Abstract: Children born by Caesarean section have modified intestinal bacterial colonization and consequently may have an increased risk of developing asthma under the hygiene hypothesis. The results of previous studies that have investigated the association between Caesarean section and asthma have been conflicting. To review published literature and perform a meta-analysis summarizing the evidence in support of an association between children born by Caesarean section and asthma. MEDLINE, Web Science, Google Scholar and PubMed were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated for each study from the reported prevalence of asthma in children born by Caesarean section and in control children. Meta-analysis was then used to derive a combined OR and test for heterogeneity in the findings between studies. Twenty-three studies were identified. The overall meta-analysis revealed an increase in the risk of asthma in children delivered by Caesarean section (OR=1.22, 95% CI 1.14, 1.29). However, in this analysis, there was evidence of heterogeneity (I(2)=46%) that was statistically significant (P<0.001). Restricting the analysis to childhood studies, this heterogeneity was markedly decreased (I(2)=32%) and no longer attained statistical significance (P=0.08). In these studies, there was also evidence of an increase (P<0.001) in the risk of asthma after Caesarean section (OR=1.20, 95% CI 1.14, 12.6). In this meta-analysis, we found a 20% increase in the subsequent risk of asthma in children who had been delivered by Caesarean section.
Publisher: Wiley
Date: 09-09-2018
DOI: 10.1111/JPC.14213
Abstract: To investigate baseline characteristics associated with complicated community-acquired pneumonia (CAPc) in Malaysian children. CAPc, such as pleural effusion and/or empyema, is on the rise, especially in Southeast Asian children, and the reasons for this are unknown. A retrospective study was conducted on all children aged 2-16 years who were admitted to the University Malaya Medical Centre with community-acquired pneumonia between 2012 and 2014. In this study, of the 343 children, 58 (17%) developed CAPc. Chinese ethnicity (P < 0.001), reduced breastfeeding duration (P = 0.003), not receiving outpatient antibiotic (P < 0.001) and exposure to parental smoking (P < 0.001) were identified as risk factors for CAPc. Markedly increased respiratory rate (P = 0.021) and thrombocytosis (P < 0.001) were noted as the clinical parameters for CAPc. This study identifies some modifiable risk to reduce the burden of pneumonia complications.
Publisher: Wiley
Date: 17-12-2019
DOI: 10.1002/PPUL.24598
Abstract: Respiratory tract infections in children can result in respiratory sequelae. We aimed to determine the prevalence of, and factors associated with persistent respiratory sequelae 1 year after admission for a lower respiratory tract infection (LRTI). This prospective cohort study involved children 1 month to 5-years-old admitted with an LRTI. Children with asthma were excluded. Patients were reviewed at 1-, 6-, and 12-months post-hospital discharge. The parent cough-specific quality of life, the depression, anxiety, and stress scale questionnaire and cough diary for 1 month, were administered. Outcomes reviewed were number of unscheduled healthcare visits, respiratory symptoms and final respiratory diagnosis at 6 and/or 12 month-review by pediatric pulmonologists. Three hundred patients with a mean ± SD age of 14 ± 15 months old were recruited. After 1 month, 239 (79.7%) returned: 28.5% (n = 68/239) had sought medical advice and 18% (n = 43/239) had cough at clinic review. Children who received antibiotics in hospital had significantly lower total cough scores (P = .005) as per the cough diary. After 1 year, 26% (n = 78/300) had a respiratory problem, predominantly preschool wheezing phenotype (n = 64/78, 82.1%). Three children had bronchiectasis or bronchiolitis obliterans. The parent cough-specific quality of life (PCQOL) was significantly lower in children with respiratory sequelae (P < .01). In logistic regression, the use of antibiotics in hospitals (adjusted odds ratio, 0.46 P = .005) was associated with reduced risk of respiratory sequelae. In children admitted for LRTI, a quarter had respiratory sequelae, of which preschool wheeze was the commonest. The use of antibiotics was associated with a lower risk of respiratory sequelae.
Publisher: Wiley
Date: 02-07-2013
DOI: 10.1002/PPUL.22698
Abstract: This case report describes an unusual outcome of ABCA3 deficiency with resolution of symptoms, normalization of chest imaging and lung function in a 9-year-old child whose sibling died of the same disease in infancy.
Publisher: Public Library of Science (PLoS)
Date: 27-01-2014
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: Springer Science and Business Media LLC
Date: 11-2019
DOI: 10.1007/S13402-019-00477-5
Abstract: In recent years, the high mobility group box-1 (HMGB1) protein, a damage-associated molecular pattern (DAMP) molecule, has been found to play multifunctional roles in the pathogenesis of colorectal cancer. Although much attention has been given to the diagnostic and prognostic values of HMGB1 in colorectal cancer, the exact functional roles of the protein as well as the mechanistic pathways involved have remained poorly defined. This systematic review aims to discuss what is currently known about the roles of HMGB1 in colorectal cancer development, growth and progression, and to highlight critical areas for future investigations. To achieve this, the bibliographic databases Pubmed, Scopus, Web of Science and ScienceDirect were systematically screened for articles from inception till June 2018, which address associations of HMGB1 with colorectal cancer. HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.
Publisher: Wiley
Date: 26-10-2010
DOI: 10.1111/J.1399-3038.2010.01052.X
Abstract: Epidemiological studies show that some children develop wheezing after 3 yr of age which tends to persist. It is unknown how this starts or whether there is a period of asymptomatic inflammation. The aim of this study is to determine whether lower airway allergic inflammation pre-exists in late onset childhood wheeze (LOCW). Follow-up study of children below 5 yr who had a non-bronchoscopic bronchoalveolar lavage (BAL) performed during elective surgery. The children had acted as normal controls. A modified ISAAC questionnaire was sent out at least 7 yr following the initial BAL, and this was used to ascertain whether any children had subsequently developed wheezing or other atopic disease (eczema, allergic rhinitis). Cellular and cytokine data from the original BAL were compared between those who never wheezed (NW) and those who had developed LOCW. Eighty-one normal non-asthmatic children were recruited with a median age of 3.2. Of the 65 children contactable, 9 (16.7%) had developed wheeze, 11 (18.5%) developed eczema and 14 (22.2%) developed hay fever. In five patients, wheeze symptoms developed mean 3.3-yr (range: 2-5 yr) post-BAL. Serum IgE and blood eosinophils were not different in the LOCW and NW, although the blood white cell count was lower in the LOCW group. The median BAL eosinophil % was significantly increased in the patients with LOCW (1.55%, IQR: 0.33 to 3.92) compared to the children who never wheezed, NW (0.1, IQR: 0.0 to 0.3, p = 0.01). No differences were detected for other cell types. There were no significant differences in BAL cytokine concentrations between children with LOCW and NW children. Before late onset childhood wheezing developed, we found evidence of elevated eosinophils in the airways. These data suggest pre-existent airways inflammation in childhood asthma some years before clinical presentation.
Publisher: Medknow
Date: 2018
Publisher: Wiley
Date: 13-03-2023
DOI: 10.1111/COA.14044
Publisher: Springer Science and Business Media LLC
Date: 27-01-2011
Abstract: Human respiratory syncytial virus (RSV) causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs). To address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers. RSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates. The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.
Publisher: Public Library of Science (PLoS)
Date: 15-10-2018
Publisher: Public Library of Science (PLoS)
Date: 09-05-2013
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Frontiers Media SA
Date: 24-04-2017
Publisher: Wiley
Date: 02-2010
Publisher: Elsevier BV
Date: 07-2021
Publisher: Springer Science and Business Media LLC
Date: 02-2011
Publisher: Springer Science and Business Media LLC
Date: 05-09-2018
Publisher: American Society for Microbiology
Date: 15-11-2010
DOI: 10.1128/JVI.00798-10
Abstract: Sendai virus (SeV) is a murine respiratory virus of considerable interest as a gene therapy or vaccine vector, as it is considered nonpathogenic in humans. However, little is known about its interaction with the human respiratory tract. To address this, we developed a model of respiratory virus infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs). These physiologically authentic cultures are comprised of polarized pseudostratified multilayered epithelium containing ciliated, goblet, and basal cells and intact tight junctions. To facilitate our studies, we rescued a replication-competent recombinant SeV expressing enhanced green fluorescent protein (rSeV/eGFP). rSeV/eGFP infected WD-PBECs efficiently and progressively and was restricted to ciliated and nonciliated cells, not goblet cells, on the apical surface. Considerable cytopathology was evident in the rSeV/eGFP-infected cultures postinfection. This manifested itself by ciliostasis, cell sloughing, apoptosis, and extensive degeneration of WD-PBEC cultures. Syncytia were also evident, along with significant basolateral secretion of proinflammatory chemokines, including IP-10, RANTES, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), interleukin 6 (IL-6), and IL-8. Such deleterious responses are difficult to reconcile with a lack of pathogenesis in humans and suggest that caution may be required in exploiting replication-competent SeV as a vaccine vector. Alternatively, such robust responses might constitute appropriate normal host responses to viral infection and be a prerequisite for the induction of efficient immune responses.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2019
DOI: 10.1007/S11325-019-01861-Z
Abstract: Polysomnography (PSG) is the gold standard in the diagnosis of obstructive sleep apnea (OSA). However, due to high cost and limited availability, this is difficult to access and often delayed. To evaluate the reliability of overnight oximetry as a screening tool for OSA diagnosis. All children suspected of OSA who underwent an overnight oximetry and subsequent PSG between January 2014 and April 2016 were studied retrospectively. The "McGill oximetry scoring" was compared with OSA diagnosis as per the American Association of Sleep Medicine. A total of 110 patients had both oximetry and PSG. Sixty-one children (56%) had normal oximetry, whereas 30 (27%) had McGill grade 2 and 19 (17%) had McGill 3 and 4. Sixty-four percent (64%) of children with normal oximetry had a normal PSG. Seventy percent (70%) of children with McGill 2 had either a normal or mild OSA on PSG. All the children with McGill 3 and 4 had moderate/severe OSA by PSG. The overall sensitivity and specificity of oximetry in identifying OSA were 63% and 78%, respectively, and the positive and negative predictive values (PPV and NPV) were 78% and 64%, respectively. The sensitivity and specificity of McGill 3 and 4 in diagnosing moderate/severe OSA on PSG were 59% and 100%, respectively, and the PPV and NPV were 100% and 78%, respectively. Overnight oximetry provides satisfactory diagnostic performance in detecting moderate and severe OSA however, a normal or McGill 2 score does not rule out OSA and a PSG is required for diagnosis.
Publisher: Elsevier BV
Date: 2012
Publisher: Medknow
Date: 05-2018
Publisher: Public Library of Science (PLoS)
Date: 19-12-2018
Publisher: Springer Science and Business Media LLC
Date: 23-06-2016
Publisher: Public Library of Science (PLoS)
Date: 14-02-2020
Publisher: Proceedings of the National Academy of Sciences
Date: 12-03-2012
Abstract: Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.
Publisher: Springer Science and Business Media LLC
Date: 06-2018
Publisher: Elsevier BV
Date: 06-2009
Publisher: Springer Science and Business Media LLC
Date: 04-09-2015
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2008
End Date: 2010
Funder: Universiti Malaya
View Funded ActivityStart Date: 2008
End Date: 2010
Funder: Boehringer Ingelheim Research Fellowship
View Funded Activity