Respiratory viruses and atypical bacteria triggering severe asthma exacerbation in children.

1. Respiratory viruses and atypical bacteria were detected in 51.0% of Hong Kong children with asthma exacerbations, which was significantly higher than the detection rate of 27.3% in children with chronic stable asthma. 2. Co-infections of two or more respiratory pathogens were more commonly found in children with asthma exacerbations (10.7%) than in patients with stable asthma (2.6%). 3. Human rhinovirus infection was a significant risk factor for asthma exacerbations. 4. There was no significant association between the severity of asthma exacerbations and respiratory viral or atypical bacterial infections. 5. Routine use of macrolide antibiotics in the treatment of childhood asthma exacerbations should be discouraged.

Natural history and predictors for progression of mild childhood obstructive sleep apnoea.

AIMS: The natural history of mild childhood obstructive sleep apnoea (OSA) was examined and factors associated with disease progression were identified. METHODS: Subjects were recruited from an epidemiological study which examined the prevalence of OSA in Chinese children aged 6-13 years. The first 56 consecutive children identified with mild OSA (apnoea-hypopnoea index 1-5) were invited for a repeat assessment 2 years after the diagnosis. RESULTS: 45 children participated in the follow-up study, in 13 of whom (29%) the OSA was found to have worsened. Compared with those in whom OSA had not worsened, the worsened OSA group had a greater increase in waist circumference, a higher prevalence of large tonsils (occupying > or =50% of the airway) at both baseline and follow-up, and a higher prevalence of habitual snoring at both baseline and follow-up. The presence of large tonsils had a positive predictive value of 53% and a negative predictive value of 83% for worsening OSA over a 2-year period. Multivariate linear regression analysis showed that the change in obstructive apnoea-hypopnoea index was associated with age at baseline (beta (SE) = -0.92 (0.34), p = 0.009), gender (male = 1; female = 0) (beta (SE) = 4.69 (1.29), p<0.001), presence of large tonsils at baseline (beta (SE) = 4.36 (1.24), p = 0.001), change in waist circumference (beta (SE) = 0.30 (0.09), p = 0.002) and persistently large tonsils (beta (SE) = 5.69 (1.36), p<0.001) over the 2-year period. CONCLUSIONS: Mild OSA in the majority of children does not resolve spontaneously. Subjects with tonsillar hypertrophy, especially boys, should be closely monitored to allow early detection of worsening OSA. Weight control should be stressed in the management of childhood OSA.

Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community based study.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is suggested to be associated with cardiac structural abnormalities and dysfunction but existing evidence is limited and the treatment effect on echocardiographic outcome remains controversial. OBJECTIVE: To examine the presence of subclinical cardiac abnormalities in childhood OSA and the effects of treatment on cardiac changes. METHODS: Polysomnography (PSG) and echocardiographic examinations were performed in 101 children aged between 6 and 13 years who were invited from a community based questionnaire survey. They were classified into a reference group (apnoea-hypopnoea index (AHI) <1, n = 35), mild OSA group (AHI 1-5, n = 39) and moderate to severe group (AHI >5, n = 27) based on the PSG results. Treatments, including adenotonsillectomy or nasal steroids, were offered to the mild and moderate to severe OSA groups. RESULTS: The moderate to severe OSA group had greater right ventricular (RV) systolic volume index (RVSVI), lower RV ejection fraction (RVEF) and higher RV myocardial performance index (RVMPI) than the reference group. They also had more significant left ventricular (LV) diastolic dysfunction and remodelling with larger interventricular septal thickness index (IVSI) and relative wall thickness than those with lower AHI values. The moderate to severe OSA group had an increased risk of abnormal LV geometry compared with the reference group (odds ratio 4.21 (95% CI 1.35 to 13.12)). Log transformed AHI was associated with RVSVI (p = 0.0002), RVEF (p = 0.0001) and RVMPI (p<0.0001), independent of the effect of obesity. Improvement in RVMPI, IVSI and E/e' were observed in those with a significant reduction in AHI (>50%) comparing 6 month with baseline data. CONCLUSIONS: OSA is an independent risk factor for subclinical RV and LV dysfunction, and improvement in AHI is associated with reversibility of these abnormalities.

Ambulatory blood pressure in children with obstructive sleep apnoea: a community based study.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is increasingly being recognised. Its effects on blood pressure (BP) elevation and hypertension are still controversial. OBJECTIVE: To evaluate the association between OSA and ambulatory BP in children. METHODS: Children aged 6-13 years from randomly selected schools were invited to undergo overnight sleep study and ambulatory BP monitoring after completing a validated OSA questionnaire. OSA was diagnosed if the obstructive apnoea-hypopnoea index (AHI) was >1, and normal controls had AHI <1 and snoring <3 nights per week. Children with OSA were subdivided into a mild group (AHI 1-5) and moderate to severe group (AHI >5). RESULTS: 306 subjects had valid sleep and daytime BP data. Children with OSA had significantly higher BP than normal healthy children during both sleep and wakefulness. BP levels increased with the severity of OSA, and children with moderate to severe disease (AHI >5) were at significantly higher risk for nocturnal systolic (OR 3.9 (95% CI 1.4 to 10.5)) and diastolic (OR 3.3 (95% CI 1.4 to 8.1)) hypertension. Multiple linear regression revealed a significant association between oxygen desaturation index and AHI with daytime and nocturnal BP, respectively, independent of obesity. CONCLUSIONS: OSA was associated with elevated daytime and nocturnal BP, and is an independent predictor of nocturnal hypertension. This has important clinical implications as childhood elevated BP predicts future cardiovascular risks. Future studies should examine the effect of therapy for OSA on changes in BP.

In vitro and clinical immunomodulatory effects of a novel Pentaherbs concoction for atopic dermatitis.

BACKGROUND: Our group recently reported a randomized and placebo-controlled clinical trial on the efficacy of a twice-daily concoction of five herbal ingredients (Pentaherbs formulation, PHF) in treating children with atopic dermatitis (AD). OBJECTIVES: To investigate the immunomodulatory effects that may be induced by PHF treatment. METHODS: We investigated the effects of PHF on cytotoxicity and proliferation of phytohaemagglutinin (PHA)- and staphylococcal enterotoxin B (SEB)-stimulated peripheral blood mononuclear cells (PBMC) isolated from buffy coat of blood donors. PHF-induced immunomodulation for five inflammatory mediators in cultured PBMC was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The effects of a 3-month, open-label study of PHF on circulating inflammatory mediators in children with AD were also assessed. RESULTS: PHF at up to 1 mg mL(-1) dose-dependently suppressed PBMC proliferation. The addition of PHF to cultured PBMC reduced supernatant concentrations of brain-derived neurotrophic factor (BDNF), interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in response to PHA, and BDNF and thymus and activation-regulated chemokine (TARC) following SEB stimulation. PHF increased epithelial cell-derived neutrophil activating peptide-78 levels in culture supernatants. At the RNA level, PHF suppressed the transcription of BDNF, TARC, IFN-gamma and TNF-alpha. Twenty-eight children with AD were treated with PHF for 3 months, and their mean plasma concentrations of BDNF and TARC decreased significantly from 1798 pg mL(-1) and 824 pg mL(-1) at baseline to 1378 pg mL(-1) and 492 pg mL(-1) (P = 0.002 and 0.013, respectively) upon study completion. CONCLUSIONS: PHF possesses in vitro and in vivo immunomodulatory properties that may mediate the clinical efficacy observed in AD treatment.

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures.

In view of the possible crosstalks between hematopoiesis and neuropoiesis, we evaluated two microenvironments, murine neonatal neural cell line C17.2 and primary embryonic aorta-gonad-mesonephros (AGM) stromal cells, on the ex vivo expansion of CD34+ cells from human cord blood. In a contact culture system, C17.2 or AGM cells significantly enhanced the expansion of CD34+ cells to a panel of early and committed hematopoietic progenitor cells. In a noncontact transwell system, pre-established C17.2 cells significantly increased the expansion of total nucleated cells, CD34+ cells and multilineage colony forming cells (P<0.01). Expanded cells were infused into nonobese diabetic/severe-combined immunodeficient mice. The engraftment of human (hu)CD45+ cells in the bone marrow of these mice was consistently higher in all the 10 experiments conducted with the support of C17.2 cells when compared with those in respective control groups (11.9 vs 2.43%, P=0.03). Using RT-PCR and Southern blot analysis, we showed that AGM and C17.2 cells expressed a panel of hematopoietic, bone morphogenetic and neurotrophic factors. Our data provided the first evidence on the promoting effects of a neural progenitor cell line on hematopoiesis at a noncontact condition. The mechanism could be mediated by the expression of multilineage regulatory factors.

Trunk anthropometry of Hong Kong Chinese infants.

BACKGROUND: Disturbed growth of the trunk may result in abnormal sternocostal relationship and a variety of pectus deformities. AIMS: The purposes of this study were to establish norms of trunk anthropometry for dysmorphology identification in the newborns and to evaluate chest circumference as a predictor for low birth weight for outborn infants where weighing scales were unavailable. STUDY DESIGN AND SUBJECTS: A total of 10,339 Chinese infants (5478 males, 4861 females) with gestation 24-42 weeks from 12 hospitals were included. The anthropometric measurements analyzed included chest circumference, inter-nipple distance, sternal length and abdominal circumference. OUTCOME MEASURES: The LMS method using maximum penalized likelihood was used to perform model fitting of the anthropometric centiles for these physical parameters. RESULTS: References tables of the four physical parameters for newborns were constructed. Chest circumference showed the highest correlation with birth weight (male: r = 0.866, female: r = 0.883). The cut-off points for chest circumference of 295 (male) and 299 mm (female) were the best predictor for low birth weight. There were also racial differences in these parameters. When compared with French infants, Chinese newborns had smaller chest circumference. CONCLUSION: These physical parameters provide useful references and aid dysmorphology diagnosis in newborns of ethnic Chinese origin.

Brief case series: montelukast, at doses recommended for asthma treatment, reduces disease severity and increases soluble CD14 in children with atopic dermatitis.

BACKGROUND: The choice of oral therapeutic agents for the treatment of atopic dermatitis (AD) in children is limited. Montelukast, a specific cysteinyl leukotriene (LT) receptor antagonist, may be useful in alleviating AD symptoms. OBJECTIVE: To evaluate the clinical and immunological effects of montelukast in children with AD. METHODS: After a 2-week run-in, children with AD were started on oral montelukast 5 mg once-daily for children < 12 years of age and 10 mg for older children. The clinical severity of AD as indicated by the SCORing Atopic Dermatitis (SCORAD) score, and serum soluble CD14 and urinary leukotriene E4 (LTE4) concentrations were evaluated at baseline and the end of a 3-month treatment period. RESULTS: Four boys and three girls, with a median (range) age of 12 (3-16) years, participated in the study. The total SCORAD was reduced in five patients (by 30-84%) and remained similar in two patients. Their median (range) SCORAD scores before and after treatment were 34.7 (16.5-54.8) and 17.0 (6.9-36.9) (p = 0.046). The intensity component of SCORAD also decreased from 5 (2-10) to 3 (1-7) (p = 0.042). Serum sCD14 levels increased significantly from 5533 (4575-6452) ng/ml to 6259 (5617-8988) ng/ml (p = 0.028), whereas urinary LTE4 levels remained the same (p = 0.735). CONCLUSIONS: Montelukast, at doses recommended for asthma treatment, resulted in over 30% reduction in the total SCORAD in some children. Treatment with montelukast may also be associated with deviation of the immune system towards the Th1-specific pathway.

Reasons for new referral non-attendance at a pediatric dermatology center: a telephone survey.

BACKGROUND: Non-attendance at pediatric dermatology outpatient clinics is a significant problem. AIM: To determine the reasons and predictors for non-attendance. METHODS: New referral non-attenders to the pediatric dermatology clinic of a university teaching hospital were contacted by telephone and reasons for non-attendance enquired about. RESULTS: Sixty-three patients (20%) did not attend the first appointment over a 15-month study period. The mean+/-SD waiting time between attenders and non-attenders was 99+/-46 days and 113+/-41 days (p=0.029). A total of 49% of attenders and 60% of non-attenders were males. Telephone contact of non-attenders who did not schedule any re-appointment spontaneously (n=54), found that the mother was the informant in 85% of cases. Approximately 80% of informants gave one reason for non-attendance; approximately 20% gave two or more reasons. The most common reasons for non-attendance were 'skin condition already improved' (46%) and 'forgot appointment' (25%). 'Long waiting time' did not appear to be a common reason for non-attendance. There was no significant association between age of patient, urgency of booking and non-attendance. CONCLUSIONS: We confirm that there is a significant non-attendance rate in pediatric dermatology new referrals. Many of the skin conditions reportedly resolve spontaneously. As there is no identifiable predictor for non-attendance apart from a longer waiting time, any maneuvers or interventions to improve attendance rate are unlikely to be significantly fruitful.

Resting energy expenditure, oxygen consumption and carbon dioxide production during sleep in children with atopic dermatitis.

BACKGROUND: Pruritus and scratching are cardinal symptoms of atopic dermatitis (AD). Sleep and growth may also be affected in children with moderate-to-severe AD. We evaluated whether resting energy expenditure (REE), oxygen consumption (VO2) and carbon dioxide production (VCO2) in various stages of sleep were influenced by the disease severity. METHODS: Disease severity was evaluated by the scoring atopic dermatitis (SCORAD) index. All-night polysomnography was performed and REE, VO2 and VCO2 were measured. RESULTS: Twenty children (13 boys and seven girls) with AD and eight controls were recruited. The median overall SCORAD for our AD patients was 36.8. The total sleep efficiency was lower in patients with severe AD than that obtained in the control group (median: 72% versus 88%; p = 0.039). When compared with mild-to-moderate disease (SCORAD40) and controls, REE, VO2 and VCO2 in patients with severe AD (SCORAD > 40) did not differ in sleep stages I and II combined, stages III and IV combined or the rapid eye movement (REM) stage. REE, VO2 and VCO2 in these sleep stages did not show significant correlation with the overall and the three components of the SCORAD scores. CONCLUSIONS: Children with AD do not appear to have significant disturbance in their resting energy consumption, oxygen consumption and carbon dioxide production during sleep. These parameters do not appear to correlate with the symptomatology of pruritus and sleep disturbance. We speculate that deranged metabolism during sleep is unlikely in children with AD.

Induced sputum in childhood asthma.

Asthma is characterised by variable degrees of airway obstruction, airway hyper-responsiveness, and chronic airway inflammation. Current guidelines emphasise that inhaled corticosteroid treatment is the mainstay of asthma therapy because it targets the underlying airway inflammation. It is prudent to use the lowest possible dose of inhaled corticosteroid compatible with good asthma control. In clinical practice, the use of or the reduction of inhaled corticosteroid dosage is based on symptoms and lung function, both of which have been shown to have a poor correlation with airway inflammation. The use of induced sputum as a marker of airway inflammation improves asthma monitoring and optimises treatment in adults. This review discusses the technique of sputum induction, its clinical application, and our experience of its use in asthmatic children.

Fever, pulmonary haemorrhage, and acute renal failure in a young girl.

Leptospirosis is rarely reported in children. It is easily treated with antibiotics but can be fatal if treatment is delayed. A 12-year-old girl was diagnosed with Weil syndrome, a severe form of leptospirosis, 10 days after returning from Mainland China. She presented with fever, hypotension, jaundice, and acute renal failure. She had used well water for bathing and swum in freshwater.

Review of children hospitalised for ingestion and poisoning at a tertiary centre.

INTRODUCTION: The main aim of this study is to determine the pattern of referrals of poisoning to a tertiary university hospital. The information will be used for poison prevention programme planning, and for educating and awareness promoting to the public. MATERIALS AND METHODS: All patients (under 21 years of age) admitted to the paediatric wards between January 1997 and December 2002 with a discharge diagnosis indicating unintentional (UP) or intentional poisoning (IP) were identified through the computerised discharge information. RESULTS: Sixty males and 98 females accounted for 161 admissions over the 6-year period. Their mean (standard deviation, SD) age was 8.2 (6.2) years. Sixty per cent of admissions involved UP. Females accounted for 47% of the UP but 86% of the IP [odds ratio of females for IP, 7.05; 95% confidence interval (CI) 2.95 to 17.28]. When compared with UP, IP patients were significantly older [mean (SD): 14.9 (1.7) versus 3.6 (3.3) years]. In 70% of the admissions, the patients ingested a single substance. Tablets and pills, especially in the IP adolescents, were more commonly ingested than syrups. The spectrum of substances ingested was vast but paracetamol, cough or cold medicines, and common adult household medications and agents accounted for the majority of medications ingested. The substances ingested were obtained at home in 81 cases (50%) and as over-the-counter medication in 33 (20%). The majority (92%) of patients presented within 24 hours of ingestion. On admission, 63% of UP and 45% of the IP were asymptomatic. No active treatment was required in 65% of patients. In IP, nearly 30% of IP who ingested paracetamol had toxic levels and received N-acteyl cysteine. A history of previous poisoning was more common and subsequent follow-up was offered to 74%. CONCLUSION: Young boys were more at risk of unintentional ingestion whereas adolescent girls were more likely to ingest medications as a gesture of suicide. Paracetamol is a frequently ingested medicinal for which an antidote is available.

Clinical features associated with nasal Staphylococcus aureus colonisation in Chinese children with moderate-to-severe atopic dermatitis.

INTRODUCTION: Staphylococcus aureus colonisation/infection is common in children with atopic dermatitis (AD). MATERIALS AND METHODS: We evaluated the nasal and body swabs of Chinese children with moderate-to-severe AD as assessed using SCORing-Atopic-Dermatitis (SCORAD) score. Swabs were taken from the right nostril, 5 flexural sites (anterior neck, antecubital fossae and popliteal fossae) and the skin area most severely affected (with oozing/crusting) for bacteriologic culture. RESULTS: Fifty-five children (30 males and 25 females) were evaluated. Moderate-to-heavy growth of S. aureus was present in 12 (22%) of the nasal swabs, and in 1 or more flexural swabs of 32 (58%) of these children. Only 7 (35%) out of the 20 patients who had swabs taken from the worst skin area had moderate-to-heavy growth of S. aureus. Significant nasal S. aureus colonisation was associated with higher total (P=0.029) and objective SCORAD scores (P=0.040), more extensive disease (P=0.025), the presence of oozing or crusting (P=0.023) and higher eosinophil counts (P=0.038). All specimens of methicillin-sensitive S. aureus were sensitive to cloxacillin and 71% to erythromycin. Methicillin-resistant S. aureus (MRSA), sensitive to vancomycin, was only isolated in 1 patient. CONCLUSIONS: In this study, S. aureus is a principal pathogen. Cloxacillin and first-generation cephalosporins have a favourable sensitivity profile even in children with moderate and severe atopic dermatitis. The anterior nares are an important harbour for S. aureus and significant nasal S. aureus colonisation was clinically associated with more extensive lesions and the presence of oozing or crusting.

Recurrent and novel mutations of GCDH gene in Chinese glutaric acidemia type I families.

Glutaric acidemia type I is caused by mutations of the glutaryl-CoA dehydrogenase (GCDH) gene resulting in loss of GCDH enzyme activity. Patients present with progressive dystonia and lesions in basal ganglia. Dietary treatment, when instituted from the early neonatal period, markedly reduces dystonia and morbidity. Early diagnosis and prenatal diagnosis will be facilitated by knowledge of locally prevalent GCDH mutations. Several common GCDH mutations have been found in different ethnic groups. GCDH mutations were studied in 5 Chinese glutaric acidemia type I families. We detected two novel recurrent mutations (A219T and IVS10-2A>C) which were found in two unrelated families. An asymptomatic carrier of IVS10-2A>C was also found on screening of 120 individuals. Other mutations were identified, including two other novel (R386G & IVS3+1G>A) and two known mutations (G178R & R355H). Fibroblasts from patients carrying the novel mutations were confirmed to be deficient for GCDH activity. This is the first report of GCDH mutations describing recurrent mutations in Chinese patients. The carrier rate of IVS10-2A>C may be particularly high in Chinese.

Plasma ghrelin and resistin concentrations are suppressed in infants of insulin-dependent diabetic mothers.

This study aimed to investigate 1) the effect of maternal diabetes mellitus on ghrelin, resistin, leptin, and insulin in term newborns; 2) the interrelationship of these metabolic hormones in the early postnatal period; and 3) the association of the hormones with anthropometric parameters at birth. A total of 120 term newborns were prospectively enrolled and categorized into three groups: 40 were infants of nondiabetic mothers (group N), 42 were infants born to mothers with gestational diabetes on low energy dietary treatment (group D), and 38 were infants born to mothers with preexisting or severe gestational diabetes who required exogenous insulin for stabilization of blood sugar during pregnancy (group I). Plasma ghrelin and resistin were significantly lower in group I than in either group N or group D infants (P < 0.048). Plasma ghrelin and subscapular skinfold thickness were significantly higher in female than in male infants [plasma ghrelin: median (interquartile range), 3.8 (3.0-4.8) vs. 3.0 (2.4-4.0) ng/ml in females and males, respectively; P = 0.003; subscapular skinfold thickness: 4.9 (4.2-5.6) vs. 4.6 (3.9-5.2) mm; P = 0.03]. In group N, plasma ghrelin was significantly, but negatively, associated with birth weight (r = -0.31; P = 0.05) and body length (r = -0.33; P = 0.04), whereas in group I, plasma ghrelin was negatively correlated with plasma resistin (r = -0.37; P = 0.02). Plasma ghrelin and resistin are suppressed in infants of insulin-dependent diabetic mothers, suggesting that the metabolic hormonal system is probably operational in fetal and early postnatal life. A low circulating ghrelin concentration may be advantageous to these infants, because a reduction in appetite may prevent excessive weight gain postnatally and counterbalances the in utero anabolic effect of hyperinsulinism in poorly controlled diabetic mothers. The suppressive effect of insulin on resistin may partially explain the excess accumulation of adipose tissue in infants of diabetic mothers by reducing the inhibitory effect of resistin on adipogenesis. Female infants have significantly higher plasma ghrelin levels than male infants, suggesting that sexual dimorphism exists in utero. This study has also shown an association between some of the metabolic hormones in specific groups of infants and thus suggests that these hormones could have interacted in utero to regulate growth and fat storage during this critical period.