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  1. Nathan AM, Muthusamy A, Thavagnanam S, Hashim A, de Bruyne J
    Pediatr Pulmonol, 2014 May;49(5):435-40.
    PMID: 24482322 DOI: 10.1002/ppul.23001
    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.
  2. Chan PW, Chew FT, Tan TN, Chua KB, Hooi PS
    Pediatr Pulmonol, 2002 Jul;34(1):47-51.
    PMID: 12112797 DOI: 10.1002/ppul.10095
    Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection (LRTI) in young children. We determined if there was a seasonal variation in Malaysia in the incidence of RSV infection in young children admitted with LRTI, and possible associations of RSV infection with local meteorological parameters. A total of 5,691 children, aged less than 24 months and hospitalized with LRTI (i.e., bronchiolitis and pneumonia) between 1982-1997, were included in this study. Nasopharyngeal samples were collected and examined for RSV by immunofluorescence, viral culture, or both. Seasonal variations were determined by analyzing the monthly RSV-positive isolation rate via time series analysis. Possible correlations with local meteorological parameters were also evaluated.RSV was isolated in 1,047 (18.4%) children. Seasonal variations in RSV infection rate were evident and peaked during the months of November, December, and January (test statistics [T] = 53.7, P < 0.001). This seasonal variation was evident for both bronchiolitis and pneumonia categories (T = 42.8 and 56.9, respectively, P < 0.001). The rate of RSV infection appeared to correlate with the monthly number of rain days (r = 0.26, P < 0.01), and inversely with the monthly mean temperature (r = -0.38, P < 0.001). In the tropics, seasonal variations in the incidence of RSV infection are evident, with an annual peak in November, December, and January. This information provides a guide for healthcare provisions and implementation of RSV prevention.
  3. Fu YC, Chi CS, Jan SL, Wang TM, Chen PY, Chang Y, et al.
    Pediatr Pulmonol, 2003 Apr;35(4):263-8.
    PMID: 12629622
    Epidemics of enterovirus 71 infections caused the rapid death of many children in Malaysia in 1997 and in Taiwan in 1998. Pulmonary edema occurred in most of the fatal cases and was considered to be neurogenic. The role of the heart was rarely investigated before. Between January 1998-January 2001, 34 consecutive patients who were admitted to the intensive care unit due to enterovirus infection were studied prospectively. Patients were divided into two groups: group I with pulmonary edema, and group II without pulmonary edema. Comparisons were made between the two groups based upon demographic, neurological, and cardiovascular manifestations. Group I consisted of 11 patients (5 boys, 6 girls; mean age, 22.8 months), and group II of 23 patients (12 boys, 11 girls; mean age, 28.8 months). There were no significant differences between the two groups in comparing sex, age, body weight, neurological severity, intracranial pressure, cell count, protein and glucose levels in cerebral spinal fluid, and blood pressure. All group I patients had left ventricular dysfunction, and their ejection fractions were significantly lower than those of patients in group II (37 +/- 11% vs. 75 +/- 6%, P < 0.001). Group I heart rates were higher than those of group II (175 +/- 24 vs. 137 +/- 25, P < 0.001). In group I, 9 patients who received conventional treatment died, and the only two survivors received left ventricular assist devices. In conclusion, the pulmonary edema of fulminant enterovirus 71 infection is associated with left ventricular failure. Left ventricular function is the major determinant of outcome. Early recognition of heart failure and aggressive cardiac intervention are life-saving. Pediatr Pulmonol. 2003; 35:263-268.
  4. Azizi BH, Henry RL
    Pediatr Pulmonol, 1990;9(1):24-9.
    PMID: 2388776
    In a cross-sectional study of 7-12 year-old primary school children in Kuala Lumpur city, lung function was assessed by spirometric and peak expiratory flow measurements. Spirometric and peak expiratory flow measurements were successfully performed in 1,214 and 1,414 children, respectively. As expected, the main predictors of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were standing height, weight, age, and sex. In addition, lung function values of Chinese and Malays were generally higher than those of Indians. In multiple regression models which included host and environmental factors, asthma was associated with significant decreases in FEV1, FEF25-75, and PEFR. However, family history of chest illness, history of allergies, low paternal education, and hospitalization during the neonatal period were not independent predictors of lung function. Children sharing rooms with adult smokers had significantly lower levels of FEF25-75. Exposures to wood or kerosene stoves were, but to mosquito repellents were not, associated with decreased lung function.
  5. Eg KP, Thomas RJ, Masters IB, McElrea MS, Marchant JM, Chang AB
    Pediatr Pulmonol, 2020 09;55(9):2444-2451.
    PMID: 32584469 DOI: 10.1002/ppul.24924
    INTRODUCTION/AIM: A validated tool for scoring bronchitis during flexible bronchoscopy (FB) is potentially useful for clinical practice and research. We aimed to develop a bronchoscopically defined bronchitis scoring system in children (BScore) based on our pilot study.

    METHODS: Children undergoing FB were prospectively enrolled. Their FB was digitally recorded and assessed (two clinicians blinded to each other and clinical history) for six features: secretion amount (six-point scale), secretion color (BronkoTest, 0-8), mucosal oedema (0-3), ridging (0-3), erythema (0-3), and pallor (0-3) based on pre-determined criteria. We correlated (Spearman's rho) each feature with bronchoalveolar lavage (BAL) neutrophil percentage (neutrophil%). BScore was then derived using models with combinations of the six features that best related to airway BAL neutrophil%. The various models of BScore were plotted against BAL neutrophil% using receiver operating characteristic (ROC) curves.

    RESULTS: We analyzed 142 out of 150 children enrolled. Eight children were excluded for unavailability of BAL cytology or FB recordings. Chronic/recurrent cough was the commonest indication for FB (75%). The median age was 3 years (IQR, 1.5-5.3 years). Secretion amount (r = 0.42) and color (r = 0.46), mucosal oedema (r = 0.42), and erythema (r = 0.30) significantly correlated with BAL neutrophil%, P 10%).

    CONCLUSION: This prospective study has developed the first validated bronchitis scoring tool in children based on bronchoscopic visual inspection of airways. Further validation in other cohorts is however required.

  6. Tan LT, Nathan AM, Jayanath S, Eg KP, Thavagnanam S, Lum LCS, et al.
    Pediatr Pulmonol, 2020 12;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.

  7. 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.

  8. Thomas RJ, Eg KP, Masters IB, McElrea M, Chang AB
    Pediatr Pulmonol, 2018 11;53(11):1510-1516.
    PMID: 30238646 DOI: 10.1002/ppul.24163
    BACKGROUND: A valid bronchoscopic scoring tool for bronchitis would be useful for clinical and research purposes as currently there are none in children. From 100 digitally recorded flexible bronchoscopies (FB), we related the various macroscopic features to airway neutrophil % to develop a FB-derived bronchitis score (BScoreexp ). We aimed to develop a FB-derived bronchitis tool.

    METHODS: FB recordings for six visualised features: secretions (amount and color) and mucosal appearance (erythema, pallor, ridging, oedema) based on pre-determined criteria on a pictorial chart were assessed by two physicians independently, blinded to the clinical history. These features were used to obtain various models of BScoreexp that were plotted against bronchoalveolar lavage (BAL) neutrophil % using a receiver operating characteristic (ROC) curve. Inter- and intra-rater agreement (weighted-kappa, K) were assessed from 30 FBs.

    RESULTS: Using BAL neutrophilia of 20% to define inflammation, the highest area under ROC (aROC) of 0.71, 95%CI 0.61-0.82 was obtained by the giving three times weightage to secretion amount and color and adding it to erythema and oedema. Inter-rater K values for secretion amount (K = 0.87, 95%CI 0.73-1.0) and color (K = 0.86, 95%CI 0.69-1.0) were excellent. Respective intra-rater K were 0.95 (0.87-1.0) and 0.68 (0.47-0.89). Other inter-rater K ranged from 0.4 (erythema) to 0.64 (pallor).

    CONCLUSION: A repeatable FB-defined bronchitis scoring tool can be derived. However, a prospective study needs to be performed with larger numbers to further evaluate and validate these results.

  9. 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 

  10. McCallum GB, Singleton RJ, Redding GJ, Grimwood K, Byrnes CA, Valery PC, et al.
    Pediatr Pulmonol, 2020 04;55(4):975-985.
    PMID: 32096916 DOI: 10.1002/ppul.24696
    OBJECTIVE: The sole prospective longitudinal study of children with either chronic suppurative lung disease (CSLD) or bronchiectasis published in the current era was limited to a single center. We sought to extend this study by evaluating the longer-term clinical and lung function outcomes and their associated risk factors in Indigenous children of adolescents from Australia, Alaska, and New Zealand who participated in our previous CSLD or bronchiectasis studies during 2004-2010.

    METHODS: Between 2015 and 2018, we evaluated 131 out of 180 (72.8%) children of adolescents from the original studies at a single follow-up visit. We administered standardized questionnaires, reviewed medical records, undertook clinical examinations, performed spirometry, and scored available chest computed tomography scans.

    RESULTS: Participants were seen at a mean age of 12.3 years (standard deviation: 2.6) and a median of 9.0 years (range: 5.0-13.0) after their original recruitment. With increasing age, rates of acute lower respiratory infections (ALRI) declined, while lung function was mostly within population norms (median forced expiry volume in one-second = 90% predicted, interquartile range [IQR]: 81-105; forced vital capacity [FVC] = 98% predicted, IQR: 85-114). However, 43 out of 111 (38.7%) reported chronic cough episodes. Their overall global rating judged by symptoms, including ALRI frequency, examination findings, and spirometry was well (20.3%), stable (43.9%), or improved (35.8%). Multivariable regression identified household tobacco exposure and age at first ALRI-episode as independent risk factors associated with lower FVC% predicted values.

    CONCLUSION: Under our clinical care, the respiratory outcomes in late childhood or early adolescence are encouraging for these patient populations at high-risk of premature mortality. Prospective studies to further inform management throughout the life course into adulthood are now needed.

  11. Wong JJ, Tan HL, Lee SW, Chang KTE, Mok YH, Lee JH
    Pediatr Pulmonol, 2020 04;55(4):1000-1006.
    PMID: 32017471 DOI: 10.1002/ppul.24674
    OBJECTIVE: This study delineates the disease trajectory of patients with pediatric acute respiratory distress syndrome (PARDS) defined by the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition, and evaluates the impact of comorbidities on outcomes.

    METHODS: This prospective study over November 2017-October 2019 was conducted in a single-center multidisciplinary pediatric intensive care unit (PICU) and included patients <21years of age with PARDS. Clinical history of those requiring mechanical ventilation for <3 days was interrogated and cases in which the diagnosis of PARDS were unlikely, identified. The impact of chronic comorbidities on clinical outcomes, in particular, pulmonary disease and immunosuppression, were analyzed.

    RESULTS: Eighty-five of 1272 PICU admissions (6.7%) met the criteria for PARDS and were included. Median age and oxygenation indexes were 2.8 (0.6, 8.3) years and 10.6 (7.6, 15.4), respectively. Overall mortality was 12 out of 85 (14.1%). Despite fulfilling criteria in 6/85 (7.1%), hypoxemia contributed by bronchospasm, mucus plugging, fluid overload, and atelectasis was quickly reversible and PARDS was unlikely in these patients. Comorbidities (57/85 [67.1%]) were not associated with worsened outcomes. However, pre-existing pulmonary disease and immunosuppression were associated with severe PARDS (12/20 [60.0%] vs 19/65 [29.2%]; P = .017), extracorporeal membrane oxygenation use (5/20 [25.0%] vs 3/65 [4.6%]; P = .016) and reduced ventilator free days (VFD) (15 [0, 19] vs 21 [6, 23]; P = .039), compared with those without them.

    CONCLUSION: A small percentage of children fulfilling the PALICC definition had quickly reversible hypoxemia with likely alternate pathophysiology to PARDS. Patients with pulmonary comorbidities and immunosuppression had a more severe course of PARDS compared with others.

  12. Su SC, Masters IB, Buntain H, Frawley K, Sarikwal A, Watson D, et al.
    Pediatr Pulmonol, 2017 04;52(4):480-486.
    PMID: 27641078 DOI: 10.1002/ppul.23606
    INTRODUCTION: Flexible bronchoscopy (FB) is the current gold standard for diagnosing tracheobronchomalacia. However, it is not always feasible and virtual bronchoscopy (VB), acquired from chest multi-detector CT (MDCT) scan is an alternative diagnostic tool. We determined the sensitivity, specificity, and positive and negative predictive values of VB compared to FB in diagnosing tracheobronchomalacia.

    METHODS: Children aged <18-years scheduled for FB and MDCT were recruited. FB and MDCT were undertaken within 30-min to 7-days of each other. Tracheobronchomalacia (mild, moderate, severe, very severe) diagnosed on FB were independently scored by two pediatric pulmonologists; VB was independently scored by two pairs (each pair = pediatric pulmonologist and radiologist), in a blinded manner.

    RESULTS: In 53 children (median age = 2.5 years, range 0.8-14.3) evaluated for airway abnormalities, tracheomalacia was detected in 37 (70%) children at FB. Of these, VB detected tracheomalacia in 20 children, with a sensitivity of 54.1% (95%CI 37.1-70.2), specificity = 87.5% (95%CI 60.4-97.8), and positive predictive value = 90.9% (95%CI 69.4-98.4). The agreement between pediatric pulmonologists for diagnosing tracheomalacia by FB was excellent, weighted κ = 0.8 (95%CI 0.64-0.97); but only fair between the pairs of pediatric pulmonologists/radiologists for VB, weighted κ = 0.47 (95%CI 0.23-0.71). There were 42 cases of bronchomalacia detected on FB. VB had a sensitivity = 45.2% (95%CI 30.2-61.2), specificity = 95.5% (95%CI 94.2-96.5), and positive predictive value = 23.2 (95%CI 14.9-34.0) compared to FB in detecting bronchomalacia.

    CONCLUSION: VB cannot replace FB as the gold standard for detecting tracheobronchomalacia in children. However, VB could be considered as an alternative diagnostic modality in children with symptoms suggestive of tracheobronchomalacia where FB is unavailable. Pediatr Pulmonol. 2017;52:480-486. © 2016 Wiley Periodicals, Inc.

  13. Binns E, Koenraads M, Hristeva L, Flamant A, Baier-Grabner S, Loi M, et al.
    Pediatr Pulmonol, 2022 Jan;57(1):38-42.
    PMID: 34644459 DOI: 10.1002/ppul.25719
    Seasonal epidemics of influenza and the respiratory syncytial virus (RSV) are the cause of substantial morbidity and mortality among children. During the global coronavirus disease 2019 (COVID-19) pandemic, the epidemiology of these viruses seems to have changed dramatically. In Australia and New Zealand, a significant decrease in both influenza and bronchiolitis have been noticed during usual peak seasons. Data from early months of winter seasons in Europe are showing similar trends. This current scenario imposes a reconsideration of the paradigm that toddlers and young schoolchildren are the main drivers of seasonal RSV outbreaks and respiratory epidemics in general. In this article, we summarize current literature, address current knowledge or role of adults in the RSV epidemiology, describe the lessons learned from pertussis epidemics and call the international community to better understand the community transmission dynamics of respiratory infections in all age groups. This can allow the establishment of better and more affordable preventive measures in the whole population level, which can ultimately save millions of child lives.
  14. Sallih ASM, Wee MW, Zaki RA, Hng SY, Eg KP, Nathan AM, et al.
    Pediatr Pulmonol, 2023 Jun;58(6):1784-1797.
    PMID: 37014160 DOI: 10.1002/ppul.26403
    BACKGROUND: Few studies have examined the impact of Coronavirus disease 2019 (COVID-19) infection on children with chronic lung disease (CLD).

    OBJECTIVE: To perform a systematic review and meta-analysis to determine the prevalence, risk factors for contracting COVID-19, and complications of COVID-19, in children with CLD.

    METHODS: This systematic review was based on articles published between January 1, 2020 and July 25, 2022. Children under 18 years old, with any CLD and infected with COVID-19 were included.

    RESULTS: Ten articles involving children with asthma and four involving children with cystic fibrosis (CF) were included in the analyses. The prevalence of COVID-19 in children with asthma varied between 0.14% and 19.1%. The use of inhaled corticosteroids (ICS) was associated with reduced risk for COVID-19 (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.40-0.90). Uncontrolled asthma, younger age, AND moderate-severe asthma were not significant risk factors for contracting COVID-19. Children with asthma had an increased risk for hospitalization (RR: 1.62, 95% CI: 1.07-2.45) but were not more likely to require assisted ventilation (RR: 0.51, 95% CI: 0.14-1.90). The risk of COVID-19 infection among children with CF was <1%. Posttransplant and cystic fibrosis-related diabetes mellitus (CFRDM) patients were at an increased risk for hospitalization and intensive care treatment.

    CONCLUSION: Hospitalizations were higher in children with asthma with COVID-19 infection. However, using ICS reduced the risk of COVID-19 infection. As for CF, postlung transplantation and CFRDM were risk factors for severe disease.

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