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  1. Lai EM, Nathan AM, de Bruyne JA, Chan LL
    Indian J Pediatr, 2015 Jun;82(6):579.
    PMID: 25640069 DOI: 10.1007/s12098-015-1698-2
    Erratum to: Indian J Pediatr DOI 10.1007/s12098-014-1565-6. In the original article, acknowledgement to a grant was missed. Below is the acknowledgement section. This study was partly funded by the UMR grant (no. UM.TNC2/RC/HTM/RP026-14HTM) awarded to AMN and JAdeB by University Malaya. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
  2. Lai EM, Nathan AM, de Bruyne JA, Chan LL
    Indian J Pediatr, 2015 May;82(5):439-44.
    PMID: 25179241 DOI: 10.1007/s12098-014-1565-6
    OBJECTIVE: To evaluate the yield of blood cultures and the impact of blood culture results on the adjustment of empiric antibiotic treatment in children hospitalised with community acquired pneumonia (CAP).

    METHODS: This was a prospective study conducted at a tertiary hospital in Malaysia, from 1st August 2010 until 31st July 2011. Children aged between 1 mo and 12 y who were admitted for CAP and had blood cultures performed before starting intravenous antibiotics were recruited. Children with congenital pneumonia, immunodeficiency, chronic cardiac or respiratory disorders, nosocomial pneumonia or those on corticosteroids, were excluded. Decision for admission was made by the attending Accident and Emergency physician.

    RESULTS: One hundred and seventy-one children were enrolled. The median age was 13 mo (range: 38 d-10 y 3 mo) and 59 % were males. Blood cultures were positive in 1.2 % (2/171) of patients while the contamination rate was 1.8 % (3/171). Doctors altered antibiotics based on blood culture results in only one patient.

    CONCLUSIONS: Both the yield and the impact of blood culture results on the adjustment of empiric antibiotic treatment were very small. There was a high contamination rate. The recommended practice of performing blood cultures in all children admitted with CAP should be reviewed.

  3. Nathan AM, de Bruyne JA, Eg KP, Thavagnanam S
    Front Pediatr, 2017;5:84.
    PMID: 28596950 DOI: 10.3389/fped.2017.00084
    Non-cystic fibrosis bronchiectasis (NCFB) has gained renewed interest, due to its increasing health-care burden. Annual mortality statistics in England and Wales showed that under 1,000 people die from bronchiectasis each year, and this number is increasing by 3% yearly. Unfortunately, there is a severe lack of well-powered, randomized controlled trials to guide clinicians how to manage NCFB effectively. Quality-of-life (QOL) measures in NCFB are an important aspect of clinical care that has not been studied well. Commonly used disease-specific questionnaires in children with NCFB are the St George's Respiratory Questionnaire, Short Form-36, the Leicester Cough Questionnaire, and the Parent Cough-Specific Quality of Life questionnaire (PC-QOL). Of these, only the PC-QOL can be used in young children, as it is a parent-proxy questionnaire. We reviewed pediatric studies looking at QOL in children with NCFB and cystic fibrosis. All types of airway clearance techniques appear to be safe and have no significant benefit over each other. Number of exacerbations and hospitalizations correlated with QOL scores, while symptom subscales correlated with lung function, worse QOL, frequent antibiotic requirements, and duration of regular follow-up in only one study. There was a correlation between QOL and age of diagnosis in children with primary ciliary dyskinesia. Other studies have shown no relationship between QOL scores and etiology of NCFB as well as CT changes. As for treatments, oral azithromycin and yoga have demonstrated some improvement in QOL scores. In conclusion, more studies are required to accurately determine important factors contributing to QOL.
  4. Ngui R, Lim YA, Chow SC, de Bruyne JA, Liam CK
    Med J Malaysia, 2011 Mar;66(1):27-31.
    PMID: 23765139 MyJurnal
    A survey was carried out to determine the prevalence of bronchial asthma and their contributing risk factors among Orang Asli subgroups living in Malaysia using IUATLD questionnaire and spirometry without being discriminatory towards age or gender. Of the 1171 distributed questionnaires, 716 (61.1%) comprising of 62.7% Semai Pahang, 51.3% Temiar, 74.2% Mah Meri, 65.6% Semai Perak, 53.6% Temuan, 53.8% Semelai, 61.1% Jakun and 67.4% Orang Kuala subgroups completed their questionnaire and were included in the data analysis. Participants comprised 549 (76.7%) children and 167 (23.3%) adults, age between 1 to 83 years old, 304 (42.5%) males and 412 (57.5%) females. The overall prevalence of bronchial asthma was 1.4% of which 1.5% was children, 1.3% adults, 1.0% male and 1.7% female, respectively. Of the 8 subgroups surveyed, 5 out of 10 confirmed asthma cases were Semai Pahang, followed by 3 cases among Mah Meri, and one case each among Temuan and Semai Perak subgroups, respectively. This study also demonstrated that the prevalence of self-reported and confirmed bronchial asthma tend to be higher among those who had close contact with pets, smoking individuals and among those who had a family history of asthma.
  5. Lum LC, Abdel-Latif ME, de Bruyne JA, Nathan AM, Gan CS
    Pediatr Crit Care Med, 2011 Jan;12(1):e7-13.
    PMID: 20190672 DOI: 10.1097/PCC.0b013e3181d505f4
    To determine the factors that predict outcome of noninvasive ventilation (NIV) in critically ill children.
  6. Shanmugam S, Nathan AM, Zaki R, Tan KE, Eg KP, Thavagnanam S, et al.
    BMC Pediatr, 2016 06 23;16:80.
    PMID: 27339265 DOI: 10.1186/s12887-016-0616-8
    BACKGROUND: Noisy breathing is a common presenting symptom in children. The purpose of this study is to (a) assess parental ability to label wheeze, (b) compare the ability of parents of children with and without asthma to label wheeze and (c) determine factors affecting parental ability to label wheeze correctly.

    METHODS: This cross-sectional study in a tertiary hospital in Kuala Lumpur, Malaysia involved parents of children with asthma. Parents of children without asthma were the control group. Eleven validated video clips showing wheeze, stridor, transmitted noises, snoring or normal breathing were shown to the parents. Parents were asked, in English or Malay, "What do you call the sound this child is making?" and "Where do you think the sound is coming from?"

    RESULTS: Two hundred parents participated in this study: 100 had children with asthma while 100 did not. Most (71.5 %) answered in Malay. Only 38.5 % of parents correctly labelled wheeze. Parents were significantly better at locating than labelling wheeze (OR 2.4, 95 % CI 1.64-3.73). Parents with asthmatic children were not better at labelling wheeze than those without asthma (OR1.04, 95 % CI 0.59-1.84). Answering in English (OR 3.4, 95 % CI 1.69-7.14) and having older children with asthma (OR 9.09, 95 % CI 3.13-26.32) were associated with correct labelling of wheeze. Other sounds were mislabelled as wheeze by 16.5 % of respondents.

    CONCLUSION: Parental labelling of wheeze was inaccurate especially in the Malay language. Parents were better at identifying the origin of wheeze rather than labelling it. Physicians should be wary about parental reporting of wheeze as it may be inaccurate.

  7. Chan PWK, Samsinah HH, Arpin HZ, Mustafa AM, de Bruyne JA
    Med J Malaysia, 2002 Jun;57(2):201-4.
    PMID: 24326651
    Eosinophilic inflammation in the airways is important in the pathogenesis of childhood asthma. Serum eosinophilic cationic protein (ECP), a marker of eosinophil activation was measured in 20 asthmatic children and 19 non-asthmatic controls. There was no difference in the socio-demography, passive smoke exposure, urinary cotinine levels and family history of asthma between the 2 groups. The median serum ECP in asthmatic children was 27.0 mcg/L (IQ1 8.8, IQ3 59.0); which was higher than in non-asthmatic controls [5.9 mcg/L (IQ1 3.0, IQ3 11.9), p=0.002]. An elevated serum ECP level can be helpful as supportive evidence in the diagnosis of bronchial asthma in Malaysia children.
  8. Ooi JM, Eg KP, Chinna K, Nathan AM, de Bruyne JA, Thavagnanam S
    J Paediatr Child Health, 2019 Apr;55(4):406-410.
    PMID: 30198175 DOI: 10.1111/jpc.14213
    AIM: 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.

    METHODS: 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.

    RESULTS: 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.

    CONCLUSION: This study identifies some modifiable risk to reduce the burden of pneumonia complications.

  9. Thavagnanam S, Cheong SY, Chinna K, Nathan AM, de Bruyne JA
    J Paediatr Child Health, 2018 May;54(5):530-534.
    PMID: 29168911 DOI: 10.1111/jpc.13789
    AIM: 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.

    METHODS: 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.

    RESULTS: 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).

    CONCLUSION: The previously identified risk factors and criteria for PICU admission need revision, and new recommendations are necessary.

  10. Nor'e SS, Sam IC, Mohamad Fakri EF, Hooi PS, Nathan AM, de Bruyne JA, et al.
    Trop Biomed, 2014 Sep;31(3):562-6.
    PMID: 25382484 MyJurnal
    Human metapneumovirus (HMPV) is a recently discovered cause of viral respiratory infections. We describe clinical and molecular epidemiology of HMPV cases diagnosed in children with respiratory infection at University of Malaya Medical Centre, Kuala Lumpur, Malaysia. The prevalence rate of HMPV between 2010 and 2012 was 1.1%, and HMPV contributed 6.5% of confirmed viral respiratory infections. The HMPV patients had a median age of 1.6 years, and a median hospital admission of 4 days. The most common clinical presentations were fever, rhinitis, pneumonia, vomiting/diarrhoea, and bronchiolitis. Based on the partial sequences of F fusion gene from 26 HMPV strains, 14 (54%) were subgenotype A2b, which was predominant in 2010; 11 (42%) were subgenotype B1, which was predominant in 2012; and 1 (4%) was subgenotype A2a. Knowledge of the circulating subgenotypes in Malaysia, and the displacement of predominant subgenotypes within 3 years, is useful data for future vaccine planning.
  11. Chan YF, Jafar FL, Nathan AM, de Bruyne JA, Hassan A, Nor'e SS, et al.
    J Infect, 2012 Jun;64(6):633-6.
    PMID: 22425558 DOI: 10.1016/j.jinf.2012.03.011
  12. Yeoh SM, Kuo IC, Wang DY, Liam CK, Sam CK, De Bruyne JA, et al.
    Int. Arch. Allergy Immunol., 2003 Nov;132(3):215-20.
    PMID: 14646382 DOI: 10.1159/000074302
    BACKGROUND: The house dust mites Dermatophagoides pteronyssinus (Der p) and Blomia tropicalis (Blo t) are the most common house dust mite species in Southeast Asia. To date, there have only been a few studies on the sensitization profile of the general populations in Southeast Asia to house dust mites. The aim of this study was to determine the profiles of Der p and Blo t sensitization among Singaporean and Malaysian subjects.

    METHODS: Enzyme-linked immunosorbent assay was used to detect specific IgE to Der p and Blo t mite crude extracts as well as purified Der p 1, Der p 2 and Blo t 5 allergens. Sera used were from 229 Singaporean subjects (124 with rhinitis, 105 without rhinitis) and 143 Malaysian subjects (94 adults and 49 children with asthma).

    RESULTS: The sensitization profile of rhinitis subjects to the dust mite allergens used in this study was as follows: Blo t extract positive: 91/124 (73%); Blo t 5 positive: 62/124 (50%); Der p extract positive: 61/124 (49%); Der p 1 positive: 53/124 (43%); Der p 2 positive: 45/124 (36%). The nonrhinitis subjects' sensitization profile was as follows: Blo t extract positive: 60/105 (57%); Blo t 5 positive: 24/105 (23%); Der p extract positive: 38/105 (36%); Der p 1 positive: 14/105 (13%); Der p 2 positive: 17/105 (16%). The study of Malaysian asthmatic adults showed that 39% of them were sensitized to Der p 1, 32% to Der p 2 and 37% to Blo t 5. Among the asthmatic children, sensitization to Blo t 5, Der p 1 and Der p 2 was 90, 57 and 39%, respectively.

    CONCLUSION: This study clearly revealed that dual sensitization to B. tropicalis and D. pteronyssinus is common in the general populations of Singapore and Malaysia. Sensitization to Blo t 5 is more prevalent than to Der p 1 and Der p 2.
  13. Nathan AM, Teh CSJ, Eg KP, Jabar KA, Zaki R, Hng SY, et al.
    Pediatr Pulmonol, 2020 02;55(2):407-417.
    PMID: 31846223 DOI: 10.1002/ppul.24598
    INTRODUCTION: 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).

    METHODOLOGY: 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.

    RESULTS: 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 

  14. Tan LT, Nathan AM, Jayanath S, Eg KP, Thavagnanam S, Lum LCS, et al.
    Pediatr Pulmonol, 2020 Dec;55(12):3477-3486.
    PMID: 33002341 DOI: 10.1002/ppul.25083
    BACKGROUND: Provision of home mechanical ventilation (HMV) to children with chronic respiratory insufficiency enhances growth and quality of life. The hypothesis was that health-related quality of life (HRQoL) and the development of these children were poorer than in healthy children.

    OBJECTIVES: To determine the HRQoL and developmental outcome of children on HMV.

    METHODS: This cross-sectional study used the TNO-AZL Preschool children's Quality Of Life (TAPQOL; <5 years old) and Health Utilities Index (HUI) 2/3 (≥5 years old) to assess the quality of life and the Schedule of Growing Skills-II to assess development. Instruments were used on children currently or previously on HMV (≥3 months) and compared with age and sex-matched controls.

    RESULTS: Sixty-five patients and 130 controls were recruited. Patients' median (interquartile range) age was 3.12 (1.65, 5.81) years. Patients had significantly lower TAPQOL scores in the domains of lung, liveliness, positive mood, social functioning, motor functioning, and communication, and lower HUI 2/3 scores in hearing, sensation, pain, speech, mobility, ambulatory, dexterity, and self-care domains. The developmental outcome of patients was poorer in all domains. However, patients had fewer behavioral problems. Those with respiratory tract disease and without comorbidities had better HRQoL and developmental scores. Having a parent as the primary caregiver was associated with better speech and language skills.

    CONCLUSIONS: HRQoL and the developmental outcome are lower in children on HMV compared to controls. Children with respiratory tract disease and without comorbidities have a better outcome. Parents play a crucial role in the acquisition of speech.

  15. Nathan AM, Loo HY, de Bruyne JA, Eg KP, Kee SY, Thavagnanam S, et al.
    Pediatr Pulmonol, 2017 04;52(4):500-507.
    PMID: 27712049 DOI: 10.1002/ppul.23569
    INTRODUCTION: Home ventilation (HV) for children is growing rapidly worldwide. The aim was to describe (1) the sociodemographic characteristics of children on HV and (2) the indications for, means and outcome of initiating HV in children from a developing country.

    METHODOLOGY: This retrospective study included patients sent home on noninvasive or invasive ventilation, over 13 years, by the pediatric respiratory unit in a single center. Children who declined treatment were excluded.

    RESULTS: Seventy children were initiated on HV: 85.7% on noninvasive ventilation, 14.3% on invasive ventilation. There was about a threefold increase from 2001-2008 (n = 18) to 2009-2014 (n = 52). Median (range) age of initiating HV was 11 (1-169) months and 73% of children were <2 years old. Common indications for HV were respiratory (57.2%), chest/spine anomalies (11.4%), and neuromuscular (10.0%). Fifty-two percent came off their devices with a median (interquartile range) usage duration of 12 (4.8, 21.6) months. Ten children (14.3%) died with one avoidable death. Children with neuromuscular disease were less likely to come off their ventilator (0.0%) compared to children with respiratory disease (62.1%). Forty-one percent of parents bought their equipment, whereas 58.6% borrowed their equipment from the medical social work department and other sources.

    CONCLUSION: HV in a resource-limited country is possible. Children with respiratory disease made up a significant proportion of those requiring HV and were more likely to be weaned off. The mortality rate was low. The social work department played an important role in facilitating early discharge. Pediatr Pulmonol. 2017;52:500-507. © 2016 Wiley Periodicals, Inc.

  16. Li L, Woo YY, de Bruyne JA, Nathan AM, Kee SY, Chan YF, et al.
    PLoS One, 2018;13(10):e0205795.
    PMID: 30321228 DOI: 10.1371/journal.pone.0205795
    OBJECTIVES: To describe the severity, human adenovirus (HAdV) type and respiratory morbidity following adenovirus pneumonia in children.

    METHODOLOGY: Retrospective review of children under 12 years of age, admitted with HAdV pneumonia, between January 2011 and July 2013, in a single centre in Malaysia. HAdV isolated from nasopharyngeal secretions were typed by sequencing hypervariable regions 1-6 of the hexon gene. Patients were reviewed for respiratory complications.

    RESULTS: HAdV was detected in 131 children of whom 92 fulfilled inclusion criteria. Median (range) age was 1.1 (0.1-8.0) years with 80% under 2 years. Twenty percent had severe disease with a case-fatality rate of 5.4%. Duration of admission (p = 0.02) was independently associated with severe illness. Twenty-two percent developed respiratory complications, the commonest being bronchiolitis obliterans (15.2%) and recurrent wheeze (5.4%). The predominant type shifted from HAdV1 and HAdV3 in 2011 to HAdV7 in 2013. The commonest types identified were types 7 (54.4%), 1(17.7%) and 3 (12.6%). Four out of the five patients who died were positive for HAdV7. Infection with type 7 (OR 8.90, 95% CI 1.32, 59.89), family history of asthma (OR 14.80, 95% CI 2.12-103.21) and need for invasive or non-invasive ventilation (OR 151.84, 95% CI 9.93-2.32E) were independent predictors of respiratory complications.

    CONCLUSIONS: One in five children admitted with HAdV pneumonia had severe disease and 22% developed respiratory complications. Type 7 was commonly isolated in children with severe disease. Family history of asthma need for invasive or non-invasive ventilation and HAdV 7 were independent predictors of respiratory complications.

  17. Li L, Woo YY, de Bruyne JA, Nathan AM, Kee SY, Chan YF, et al.
    PLoS One, 2018;13(12):e0209720.
    PMID: 30566518 DOI: 10.1371/journal.pone.0209720
    [This corrects the article DOI: 10.1371/journal.pone.0205795.].
  18. Nathan AM, Teh CSJ, Jabar KA, Teoh BT, Tangaperumal A, Westerhout C, et al.
    PLoS One, 2020;15(2):e0228056.
    PMID: 32059033 DOI: 10.1371/journal.pone.0228056
    INTRODUCTION: Pneumonia in children is a common disease yet determining its aetiology remains elusive.

    OBJECTIVES: To determine the a) aetiology, b) factors associated with bacterial pneumonia and c) association between co-infections (bacteria + virus) and severity of disease, in children admitted with severe pneumonia.

    METHODS: A prospective cohort study involving children aged 1-month to 5-years admitted with very severe pneumonia, as per the WHO definition, over 2 years. Induced sputum and blood obtained within 24 hrs of admission were examined via PCR, immunofluorescence and culture to detect 17 bacteria/viruses. A designated radiologist read the chest radiographs.

    RESULTS: Three hundred patients with a mean (SD) age of 14 (±15) months old were recruited. Significant pathogens were detected in 62% of patients (n = 186). Viruses alone were detected in 23.7% (n = 71) with rhinovirus (31%), human metapneumovirus (HMP) [22.5%] and respiratory syncytial virus (RSV) [16.9%] being the commonest. Bacteria alone was detected in 25% (n = 75) with Haemophilus influenzae (29.3%), Staphylococcus aureus (24%) and Streptococcus pneumoniae (22.7%) being the commonest. Co-infections were seen in 13.3% (n = 40) of patients. Male gender (AdjOR 1.84 [95% CI 1.10, 3.05]) and presence of crepitations (AdjOR 2.27 [95% CI 1.12, 4.60]) were associated with bacterial infection. C-reactive protein (CRP) [p = 0.007]) was significantly higher in patients with co-infections but duration of hospitalization (p = 0.77) and requirement for supplemental respiratory support (p = 0.26) were not associated with co-infection.

    CONCLUSIONS: Bacteria remain an important cause of very severe pneumonia in developing countries with one in four children admitted isolating bacteria alone. Male gender and presence of crepitations were significantly associated with bacterial aetiology. Co-infection was associated with a higher CRP but no other parameters of severe clinical illness.

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