Outcomes of neonatal congenital diaphragmatic hernia in a non-ECMO center in a middle-income country: a retrospective cohort study.

BACKGROUND: Most studies examining survival of neonates with congenital diaphragmatic hernia (CDH) are in high-income countries. We aimed to describe the management, survival to hospital discharge rate, and factors associated with survival of neonates with unilateral CDH in a middle-income country. METHODS: We retrospectively reviewed the medical notes of neonates with unilateral CDH admitted to a pediatric intensive care unit (PICU) in a tertiary referral center over a 15-year period, from 2003-2017. We described the newborns' respiratory care pathways and then compared baseline demographic, hemodynamic, and respiratory indicators between survivors and non-survivors. The primary outcome measure was survival to hospital discharge. RESULTS: Altogether, 120 neonates were included with 43.3% (52/120) diagnosed antenatally. Stabilization occurred in 38.3% (46/120) with conventional ventilation, 13.3% (16/120) with high-frequency intermittent positive-pressure ventilation, and 22.5% (27/120) with high frequency oscillatory ventilation. Surgical repair was possible in 75.0% (90/120). The overall 30-day survival was 70.8% (85/120) and survival to hospital discharge was 66.7% (80/120). Survival to hospital discharge tended to improve over time (p > 0.05), from 56.0% to 69.5% before and after, respectively, a service reorganization. For those neonates who could be stabilized and operated on, 90.9% (80/88) survived to hospital discharge. The commonest post-operative complication was infection, occurring in 43.3%. The median survivor length of stay was 32.5 (interquartile range 18.8-58.0) days. Multiple logistic regression modelling showed vaginal delivery (odds ratio [OR] = 4.8; 95% confidence interval [CI] [1.1-21.67]; p = 0.041), Apgar score [Formula: see text] 7 at 5 min (OR = 6.7; 95% CI [1.2-36.3]; p = 0.028), and fraction of inspired oxygen (FiO2) < 50% at 24 h (OR = 89.6; 95% CI [10.6-758.6]; p < 0.001) were significantly associated with improved survival to hospital discharge. CONCLUSIONS: We report a survival to hospital discharge rate of 66.7%. Survival tended to improve over time, reflecting a greater critical volume of cases and multi-disciplinary care with early involvement of the respiratory team resulting in improved transitioning from PICU. Vaginal delivery, Apgar score [Formula: see text] 7 at 5 min, and FiO2 < 50% at 24 h increased the likelihood of survival to hospital discharge.

Comparison of nocturnal pulse oximetry with polysomnography in children with sleep disordered breathing.

PURPOSE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Predictive risk factors for complicated pneumonia in Malaysian children.

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.

Relapse of chronic melioidosis in a paediatric cystic fibrosis patient: first case report from Malaysia.

BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis, which is a potentially life threatening disease endemic in Southeast Asian countries. In Malaysia, cystic fibrosis (CF) is an uncommon condition. The association between CF and B.pseudomallei infections has been reported previously. However, this is the first case report of a pediatric melioidosis relapse and co-infection with other Gram-negative bacteria in Malaysia. CASE PRESENTATION: A 14-year-old Chinese Malaysian boy presented with a history of recurrent pneumonia, poor growth and steatorrhoea since childhood, and was diagnosed with CF. B. pseudomallei was cultured from his sputum during three different admissions between 2013 and 2016. However, the patient succumbed to end stage of respiratory failure in 2017 despite antibiotics treatment against B.pseudomallei. The isolates were compared using multilocus-sequence typing and repetitive-element polymerase chain reaction (PCR), and confirmed that two of the isolates were of same sequence type, which may indicate relapse. CONCLUSIONS: CF patients should be aware of melioidosis in endemic regions, as it is an emerging infectious disease, especially when persistent or recurrent respiratory symptoms and signs of infection occur. The high prevalence rates of melioidosis in Malaysia warrants better management options to improve quality of life, and life expectancy in patients with CF. Travel activities to endemic regions should also be given more consideration, as this would be crucial to identify and initiate appropriate empiric treatment.

Serotypes & penicillin susceptibility of Streptococcus pneumoniae isolated from children admitted to a tertiary teaching hospital in Malaysia.

BACKGROUND & OBJECTIVES: STREPTOCOCCUS PNEUMONIAE: (pneumococcus) is a highly invasive extracellular pathogen that causes diseases such as pneumonia, otitis media and meningitis. This study was undertaken to determine the serotype diversity and penicillin susceptibility of S. pneumoniae isolated from paediatric patients in a tertiary teaching hospital in Malaysia. METHODS: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated. RESULTS: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F. INTERPRETATION & CONCLUSIONS: Our study revealed the distribution of various serotypes in S. pneumoniae isolates obtained from children in a teaching hospital at Kuala Lumpur, Malaysia and decreasing rates of penicillin resistance among them. The shifts in serotypes and susceptibility to penicillin from time to time have been observed. Continuous monitoring and surveillance are pivotal for better infection control and management of pneumococcal infections among children.

Pre-operative parameters do not reliably identify post-operative respiratory risk in children undergoing adenotonsillectomy.

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.

Parents are poor at labelling wheeze in children: a cross-sectional study.

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.

Cross cultural translation, adaptation and reliability of the Malay version of the Canadian Acute Respiratory Illness and Flu Scale (CARIFS).

BACKGROUND: The Canadian Acute Respiratory Illness and Flu Scale (CARIFS) is a parent-proxy questionnaire that assesses severity of acute respiratory infections in children. The aim was to (a) perform a cross-cultural adaptation and (b) prove that the Malay CARIFS is a reliable tool. FINDINGS: The CARIFS underwent forward and backward translations as recommended by international guidelines. A pilot study was performed on the harmonised version and the final version of the Malay version of CARIFS was produced. A test-retest, 1 h apart, was then performed on parents with children less than 13 years old, admitted with a respiratory tract infection. Parents of children with asthma and who were not eloquent in Malay, were excluded. The data was analysed for consistency (Cronbach's alpha) and reliability (test-retest co-efficient). Thirty-three parents were recruited. Children were aged median (IQR) 6 (2.8, 13.3) months with a male: female ratio of 22:11 and 88% were Malays. Parents were interviewed at median (IQR) 6 (3, 11.5) days of admission. The Cronbach's α coefficient was 0.70 for all items. The test-retest reliability analysis had a minimum and maximum intraclass correlation coefficient of 0.63 and 0.97 respectively. Clinically, the longer patients were admitted, the lower the severity score (r = -0.35, p < 0.05), indicating that they were getting better. CONCLUSION: The Malay version of CARIFS is a valid and reliable tool to determine severity of respiratory illness in children. Parent-centred questionnaires are useful and should be an adjunct to other methods, in monitoring response to treatment.

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo.

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.

Pulmonary dysfunction in overweight and obese children with obstructive sleep apnoea.

INTRODUCTION: Overweight and obese children are at risk of obstructive sleep apnoea (OSA) and abnormal pulmonary function (PF). AIM: Investigate the relationship between body mass index (BMI), OSA on PF in children. MATERIALS & METHOD: Seventy-four children were recruited. Mixed obstructive apnoea-hypopnea index (MOAHI), BMI, oxygen saturation (SpO2 ), forced expiratory volume one second (FEV1 ), forced vital capacity (FVC) and fractionated exhaled nitric oxide (FeNO) were measured. RESULTS: Twenty-four and thirty children had mild OSA and moderate-to-severe OSA respectively. BMI correlated negatively with SpO2 nadir (r = -.363, p = .001). FVC, FEV1 and nadir SpO2 values decreased with OSA severity (p < .001). The odds of a child with OSA having an abnormal spirometry was 3.16 (95% CI: 1.08, 9.22). There was significant association between FeNO and AHI (r = .497, <.001). DISCUSSION: Overweight and obese children with OSA have significant abnormalities in pulmonary function independent of BMI. OSA severity and elevated FeNO also correlated with diminishing lung function.

Cytopathogenesis of Sendai virus in well-differentiated primary pediatric bronchial epithelial cells.

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.

Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effects of IL-13 on mucociliary differentiation of pediatric asthmatic bronchial epithelial cells.

Goblet cell hyperplasia (GCH) and decreased ciliated cells are characteristic of asthma. We examined the effects of IL-13 (2 and 20 ng/mL) on in vitro mucociliary differentiation in pediatric bronchial epithelial cells (PBECs) of normal PBEC [PBEC(N)] and asthmatic PBEC [PBEC(A)] children. Markers of differentiation, real-time PCR for MUC5AC, MUC5AC ELISA, and transepithelial electrical resistance (TEER) were assessed. Stimulation with 20 ng/mL IL-13 in PBEC(N) resulted in GCH [20 ng/mL IL-13: mean, 33.8% (SD, 7.2) versus unstimulated: mean, 18.9% (SD, 5.0); p < 0.0001] and decreased ciliated cell number [20 ng/mL IL-13: mean, 8% (SD, 5.6) versus unstimulated: mean, 22.7% (SD,7.6); p < 0.01]. PBEC(N) stimulated with 20 ng/mL IL-13 resulted in >5-fold (SD, 3.2) increase in MUC5AC mRNA expression, p < 0.001, compared with unstimulated PBEC(N). In PBEC(A), GCH was also seen [20 ng/mL IL-13: mean, 44.7% (SD, 16.4) versus unstimulated: mean, 30.4% (SD, 13.9); p < 0.05] with a decreased ciliated cell number [20 ng/mL IL-13: mean, 8.8% (SD, 7.5) versus unstimulated: mean, 16.3% (SD, 4.2); p < 0.001]. We also observed an increase in MUC5AC mRNA expression with 20 ng/mL IL-13 in PBEC(A), p < 0.05. IL-13 drives PBEC(N) toward an asthmatic phenotype and worsens the phenotype in PBEC(A) with reduced ciliated cell numbers and increased goblet cells.

Obstructive sleep apnoea syndrome (OSAS) as a risk factor for secondary osteoporosis in children.

Repetitive hypoxia seen in obstructive sleep apnoea syndrome (OSAS) may affect bone metabolism increasing the risk for secondary osteoporosis. This study investigates the association between OSAS in children and secondary osteoporosis. This cross-sectional study included 150 children aged 10-17 years: 86 with OSAS and 64 with no OSAS. OSAS was confirmed by polysomnography. Quantitative ultrasound (QUS) of calcaneum measuring speed of sound (SoS) and broadband ultrasound attenuation (BUA) were collected. Other parameters collected including bone profile, vitamin D levels, physical activity scoring and dietary calcium intake. Majority were male and Malay ethnicity. OSAS children were mostly obese (84%) and 57% had moderate to severe OSAS. Most had lower physical activities scores. Mean (SD) phosphate and Alkaline phosphatase were lower in OSA children compared to controls: PO4, p = 0.039 and ALP, p < 0.001. Using both single and multivariate analysis, children with OSAS had a lower mean SoS value, p < 0.001 and p = 0.004 respectively after adjusting for age, BMI and bone profile. Children with OSAS had lower SoS suggesting risk for secondary osteoporosis. QUS calcaneus is a non-invasive, feasible tool and can be used to screen risk of osteoporosis in children. Further bone mineral density assessment is needed in these groups of children to confirm diagnosis of osteoporosis.

IL-1α and colorectal cancer pathogenesis: Enthralling candidate for anti-cancer therapy.

Inflammation has been well-established as a hallmark of colorectal cancer (CRC). Interleukin-1 alpha (IL-1α) is one of the primary inflammatory mediators driving the pathogenesis of inflammation-associated CRC. This systematic review presents the roles of IL-1α in the pathogenesis of the disease. Bibliographic databases PubMed, Science Direct, Scopus and Web of Science were systematically searched for articles that addresses the relationship between IL-1α and colorectal cancer. We highlighted various mechanisms by which IL-1α promotes the pathogenesis of CRC including enhancement of angiogenesis, metastasis, resistance to therapy, and inhibition of tumour suppressive genes. We also discussed the potential mechanisms by which IL-1α expression is induced or secreted in various studies. Beyond these, the systematic review also highlights several potential therapeutic strategies which should be further explored in the future; to target IL-1α and/or its associated pathways; paving our way in finding effective treatments for CRC patients.

WRISTOX2 is a reliable tool to diagnose obstructive sleep apnoea syndrome.

INTRODUCTION: Overnight pulse oximetry is an alternative to polysomnography (PSG) in diagnosing obstructive sleep apnoea syndrome, but its sensitivity is reported to be low. AIMS: To determine the (a) diagnostic accuracy, interobserver reliability and reliable oxygen desaturation index of 4% (ODI4) score at diagnosing obstructive sleep apnoea syndrome in children and (b) correlation between the apnoea hypopnoea index (AHI) with ODI4 and oxygen nadir between both PSG and oximetry. METHODS: This cross-sectional study included children aged 1-18 years old, undergoing a fully attended overnight PSG for suspected obstructive sleep apnoea syndrome. The Nonin 3150 WristOx2 ™ [Fig. 2] was worn simultaneously during the PSG. Poor oximetry recordings were excluded. Pulse oximetry was scored using the McGill Oximetry Score (MOS) whereby a score of 2-4 was positive for OSAS. Specificity, sensitivity, positive predictive values (PPV), negative predictive values (NPV) and interobserver reliability of the WristOx2 were calculated. RESULTS: One hundred and sixty-two children with a mean (SD) age of 9.3 (±3.5) years (range 2 years 6 months old - 17 years old) were included after excluding 18 children (poor oximetry data [n = 16] and incomplete PSG [n = 2]). Interobserver agreement of the WristOx2 was 0.8763 (95% CI:0.80, 0.95). WristOx2 had a sensitivity 50%, specificity 96.7%, PPV 96% and NPV 53% at diagnosing OSAS. ODI4 ≥ 2 events/hour in oximetry had a sensitivity of 97.6% and negative predictive value of 85.7% at diagnosing OSA. CONCLUSION: Overnight pulse oximetry with the Nonin 3150 WristOx2 ™ is an accurate and reliable tool in diagnosing significant OSAS in children.

A 3-D well-differentiated model of pediatric bronchial epithelium demonstrates unstimulated morphological differences between asthmatic and nonasthmatic cells.

There is a need for reproducible and effective models of pediatric bronchial epithelium to study disease states such as asthma. We aimed to develop, characterize, and differentiate an effective, an efficient, and a reliable three-dimensional model of pediatric bronchial epithelium to test the hypothesis that children with asthma differ in their epithelial morphologic phenotype when compared with nonasthmatic children. Primary cell cultures from both asthmatic and nonasthmatic children were grown and differentiated at the air-liquid interface for 28 d. Tight junction formation, MUC5AC secretion, IL-8, IL-6, prostaglandin E2 production, and the percentage of goblet and ciliated cells in culture were assessed. Well-differentiated, multilayered, columnar epithelium containing both ciliated and goblet cells from asthmatic and nonasthmatic subjects were generated. All cultures demonstrated tight junction formation at the apical surface and exhibited mucus production and secretion. Asthmatic and nonasthmatic cultures secreted similar quantities of IL-8, IL-6, and prostaglandin E2. Cultures developed from asthmatic children contained considerably more goblet cells and fewer ciliated cells compared with those from nonasthmatic children. A well-differentiated model of pediatric epithelium has been developed that will be useful for more in vivo like study of the mechanisms at play during asthma.

Does airway allergic inflammation pre-exist before late onset wheeze in children?

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.