Albert M. Li

Clinical presentations and outcome of severe acute respiratory syndrome in children

Summary Hong Kong has been severely affected by severe acute respiratory syndrome (SARS). Contact in households and healthcare settings is thought to be important for transmission, putting children at particular risk. Most data so far, however, have been for adults. We prospectively followed up the first ten children with SARS managed during the early phase of the epidemic in Hong Kong. All the children had been in close contact with infected adults. Persistent fever, cough, progressive radiographic changes of chest and lymphopenia were noted in all patients. The children were treated with high-dose ribavirin, oral prednisolone, or intravenous methylprednisolone, with no short-term adverse effects. Four teenagers required oxygen therapy and two needed assisted ventilation. None of the younger children required oxygen supplementation. Compared with adults and teenagers, SARS seems to have a less aggressive clinical course in younger children.

A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils)

Asthma severity and control can be measured both subjectively and objectively. Traditionally asthma treatments have been individualised using symptoms and spirometry/peak flow. Increasingly treatment tailored in accordance with inflammatory markers (sputum eosinophil counts or fractional exhaled nitric oxide (FeNO) data) is advocated as an alternative strategy. The objective of this review was to evaluate the efficacy of tailoring asthma interventions based on inflammatory markers (sputum analysis and FeNO) in comparison with clinical symptoms (with or without spirometry/peak flow) for asthma-related outcomes in children and adults. Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles were searched. The last searches were in February 2009. All randomised controlled comparisons of adjustment of asthma treatment based on sputum analysis or FeNO compared with traditional methods (primarily clinical symptoms and spirometry/peak flow) were selected. Results of searches were reviewed against predetermined criteria for inclusion. Relevant studies were selected, assessed and data extracted independently by at least two people. The trial authors were contacted for further information. Data were analysed as ‘intervention received’ and sensitivity analyses performed. Six (2 adults and 4 children/adolescent) studies utilising FeNO and three adult studies utilising sputum eosinophils were included. These studies had a degree of clinical heterogeneity including definition of asthma exacerbations, duration of study and variations in cut-off levels for percentage of sputum eosinophils and FeNO to alter management in each study. Adults who had treatment adjusted according to sputum eosinophils had a reduced number of exacerbations compared with the control group (52 vs 77 patients with ≥1 exacerbation in the study period; p=0.0006). There was no significant difference in exacerbations between groups for FeNO compared with controls. The daily dose of inhaled corticosteroids at the end of the study was decreased in adults whose treatment was based on FeNO in comparison with the control group (mean difference −450.03 μg, 95% CI −676.73 to −223.34; p<0.0001). However, children who had treatment adjusted according to FeNO had an increase in their mean daily dose of inhaled corticosteroids (mean difference 140.18 μg, 95% CI 28.94 to 251.42; p=0.014). It was concluded that tailoring of asthma treatment based on sputum eosinophils is effective in decreasing asthma exacerbations. However, tailoring of asthma treatment based on FeNO levels has not been shown to be effective in improving asthma outcomes in children and adults. At present, there is insufficient justification to advocate the routine use of either sputum analysis (due to technical expertise required) or FeNO in everyday clinical practice.

Hepatic steatosis in obese Chinese children

OBJECTIVES: The aims of our study were: (1) to determine the prevalence of asymptomatic hepatic steatosis and presumed nonalcoholic steatohepatitis, in our local population of obese Chinese children referred for medical assessment; and (2) to assess the correlation between severity of ultrasonographic hepatic steatosis and degree of obesity, insulin resistance and serum biochemical abnormalities.DESIGN: Cross-sectional study.METHODS: In total, 84 obese children, 25 girls and 59 boys with median age and body mass index (BMI) of 12.0 years (interquartile range (IR): 9.5–14.0) and 30.3 kg/m2 (IR: 27.1–33.4), respectively, referred for medical assessment were studied. All subjects underwent physical examination, anthropometric and dual energy X-ray absorptiometry (DEXA) scan measurements and real-time ultrasonographic (US) examination of the liver. Fasting blood samples were collected for the measurement of liver function, hepatitis status, levels of serum glucose and insulin and lipid profile. Degree of fatty infiltration of the liver was graded according to ultrasonic appearance of liver echotexture, liver–diaphragm differentiation in echo amplitude, hepatic echo penetration and clarity of hepatic blood vessels.RESULTS: All recruited subjects had no history of alcohol abuse and tests for Hepatitis B or C virus were negative. Thorough examination showed all of them to be in general good health without signs of chronic liver disease. Hepatic steatosis identified by defined ultrasonic appearances was diagnosed in 65 subjects (77%); 17 girls and 48 boys. The severity of fatty liver was positively related to anthropometric measurements including BMI, waist and hip circumference, subscapular skinfold thickness; insulin resistance markers [QUICKI and homeostasis model assessment (HOMA)], and hypertriglyceridaemia. Multvariate ordinal regression analysis showed that BMI and raised alanine aminotransferase (ALT) were positively associated with fatty liver. Combination of hepatic steatosis with raised ALT (presumptive NASH) was found in 19 subjects (24%). This group of patients had significantly higher waist hip ratio and conicity index compared to those with isolated hepatic steatosis. Boys with presumed NASH were also found to have significantly higher insulin resistance.CONCLUSION: Nonalcoholic fatty liver disease (NAFLD) was common among our cohort of obese children referred for medical assessment. The prevalence of simple steatosis and presumed NASH was 77 and 24%, respectively. The severity of US steatosis was positively correlated with BMI, raised ALT, insulin resistance and hypertryglyceridaemia. Ultrasonography being noninvasive and readily available could be used for the monitoring of the progression of hepatic steatosis. Further longitudinal studies are required to determine the natural disease progression and the role of insulin resistance and other factors in the pathophysiology of NAFLD.

A controlled study of sleep related disordered breathing in obese children

Background: Unlike the adult sleep related disordered breathing (SDB) patients who are typically obese, the relation between obesity and childhood SDB is not clear. Aims: To investigate whether obese children are more at risk of obstructive SDB when compared to normal population, and whether this risk is potentiated by the presence of pharyngeal lymphoid tissue. Methods: Forty six obese children (age 10.8 (SD 2.3) years; BMI 27.4 (SD 5.1)), and 44 sex and age matched normal weight children (age 11.7 (SD 2.1) years; BMI 18 (SD 1.8)) were studied. All children underwent a set of physical examinations (including the upper airways) and sleep studies. Results: The obese children were different from the normal weight children in terms of type (predominantly obstructive), frequency, and severity of respiratory disturbances. Depending on the criteria used, 26% or 32.6% of obese children had SDB; 2.3% of normal controls had OAI ⩾1 and 4.5% had RDI ⩾5. Presence of SDB was related to presence of tonsils (size >2; range 0–4) (OR 12.67, 95% CI 2.14 to 75.17) and BMI (OR 1.20, 95% CI 1.08 to 1.33). Conclusions: Results suggest that obese children are at increased risk of obstructive SDB; the presence of any pharyngeal lymphoid tissue enlargement in obese children should therefore be aggressively managed.

The effects of obesity on pulmonary function

Aims: (1) To determine the predominant pulmonary function abnormality in our population of obese children; and (2) to assess the correlation between the severity of lung function impairment and the degree of obesity as assessed by dual energy x ray absorptiometry (DEXA). Methods: Sixty four obese patients underwent physical examination, standardised pulmonary function tests (spirometry, lung volumes, and single breath diffusion capacity for carbon monoxide), and DEXA scan measurements. The trunk and subtotal (total − head) body fat mass were used as surrogate index of body adiposity. Results: Sixteen girls and 48 boys with median age and body mass index (BMI) of 12 years (interquartile range (IQR): 10–14) and 30.1 kg/m2 (IQR: 27.2–32.8) respectively were studied. None of the patients had clinical evidence of cardiopulmonary disease. Reduction in functional residual capacity (median FRC 93% predicted, IQR: 68.5–116.5%) and impairment of diffusion capacity (median DLco 83.5% predicted, IQR: 70.0–100.7%) were the most common abnormalities in our cohort, being observed in 30 (46%) and 21 (33%) patients respectively. Obstructive ventilatory impairment was found in three patients. There was significant negative correlation between the degree of reduction of FRC but not DLco with DEXA scan measurements, but such a relation was not found when BMI was used as the indicator of obesity. Conclusion: Reduction in FRC and diffusion impairment were the commonest abnormalities found in our cohort of obese patients. Reduction in static lung volume was correlated with the degree of obesity.

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.

Waist circumference and body mass index in Chinese children: cutoff values for predicting cardiovascular risk factors

Background:Body mass index (BMI) and waist circumference (WC) correlate with cardiovascular (CV) risk factors in childhood which track into adulthood. WC provides a measure of central obesity, which has been specifically associated with CV risk factors. Reference standards for WC, and for WC and BMI risk threshold values are not established in Chinese children.Objectives:To construct reference percentile charts of WC, establish relationships between WC, BMI and other risk factors, and propose WC and BMI threshold values predictive of CV risk factors in Hong Kong ethnic Chinese children.Methods:Weight, height, waist and hip circumference were measured in 2593 (52% boys, 47% girls) randomly sampled Hong Kong school children aged 6–12 years. In 958 of these and 97 additional overweight children (n=1055), the relationships between WC, BMI, waist/hip and waist/height ratio and six age-adjusted CV risk factors (>85% percentile levels of blood pressure (BP), fasting triglycerides, low-density lipoprotein (LDL) cholesterol, glucose and insulin levels, and <15% percentile levels of high-density lipoprotein (HDL) cholesterol) were studied. Receiver-operating characteristic analysis was employed to derive optimal age-adjusted sex-specific WC and BMI thresholds for predicting these measures of risk.Results:WC percentiles were constructed. WC correlated slightly more than BMI with CV risk factors and most strongly with insulin and systolic BP, but poorly or not with LDL and glucose. Optimal WC and BMI risk thresholds for predicting four of these six CV risk factors were ca. the 85th percentiles (sensitivities ∼0.8, specificities ∼0.87) with age-specific cutoff values in girls/boys from ∼57/58 to ∼71/76 cm and 17/18 to 22/23 kg/m2.Conclusion:These are the first set of WC reference data for Chinese children. WC risk cutoff values are proposed which, despite a smaller waist in Chinese children, are similar to those reported for American children. WC percentiles may reflect population risk.

Waist circumference and waist-to-height ratio of Hong Kong Chinese children

BackgroundCentral body fat is a better predictor than overall body fat for cardiovascular (CV) risk factors in both adults and children. Waist circumference (WC) has been used as a proxy measure of central body fat. Children at high CV risk may be identified by WC measurements. Waist-to-height ratio (WHTR) has been proposed as an alternative, conveniently age-independent measure of CV risk although WHTR percentiles have not been reported. We aim to provide age- and sex-specific reference values for WC and WHTR in Hong Kong Chinese children.MethodsCross sectional study in a large representative sample of 14,842 children aged 6 to 18 years in 2005/6. Sex-specific descriptive statistics for whole-year age groups and smoothed percentile curves of WC and WHTR were derived and presented.ResultsWC increased with age, although less after age 14 years in girls. WHTR decreased with age (particularly up to age 14). WHTR correlated less closely than WC with BMI (r = 0.65, 0.59 cf. 0.93, 0.91, for boys and girls respectively).ConclusionReference values and percentile curves for WC and WHRT of Chinese children and adolescents are provided. Both WC and WHTR are age dependent. Since the use of WHRT does not obviate the need for age-related reference standards, simple WC measurement is a more convenient method for central fat estimation than WHRT.

The C−159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children

Activation of macrophages through CD14 by microbes is crucial in inducing immunity by type 1 T helper cells. A C‐to‐T polymorphism at position −159 of CD14 was associated with serum total IgE level in Caucasians but not in Japanese subjects. The objective of this study is to determine whether this polymorphic marker is associated with atopy and asthma phenotypes in Chinese children. Restriction fragment length polymorphism was used to characterize CD14/−159 genotypes. Microparticle immunoassay was used to measure serum total IgE level; fluorescent enzyme immunoassay was performed to measure serum concentrations of specific IgE to aeroallergens; and enzyme‐linked immunosorbent assay was used to measure serum levels of soluble CD14 (sCD14). Lung function in asthmatics was assessed by spirometry. Two hundred and fifty‐eight patients and 92 control children were recruited. Their mean serum total IgE concentrations were 331 and 74 kIU/l, respectively (p < 0.0001). Atopy, defined as the presence of at least one allergen‐specific IgE in serum, was found in 220 (85%) patients and in 41 (45%) controls (p < 0.0001). Serum sCD14 levels were significantly associated with CD14/−159 genotypes (p = 0.004). Atopic subjects with CC genotype in CD14/−159 had the highest serum total IgE levels compared with CT and TT genotypes, with the respective mean values being 661, 427 and 380 kIU/l (p = 0.015). Similarly, a higher proportion of subjects with CC genotype had increased serum total IgE concentration (p = 0.039). This polymorphic marker was not associated with asthma or aeroallergen sensitization in our cohort. Our results suggest that the C−159T of CD14 was associated with serum total IgE concentration in atopic Chinese children.

Use of tonsil size in the evaluation of obstructive sleep apnoea

Aims: (1) To determine the extent to which tonsil size contributes to the severity of obstructive sleep apnoea (OSA) in children; and (2) to assess the use of tonsillar-pharyngeal (TP) ratio in differentiating patients with different severity of OSA. Methods: Lateral neck radiograph was performed on 35 children referred consecutively to a university paediatric chest clinic for suspected OSA secondary to tonsillar hypertrophy. The tonsil size was determined by measuring the TP ratio on the radiographs. The severity of OSA was assessed by overnight polysomnography. Results: A total of 24 boys and 11 girls (median age 6.2 years) were studied. All presented with symptoms of OSA, and tonsillar hypertrophy was detected on clinical examination. The median apnoea–hypopnoea index (AHI) was 16.93 (interquartile range: 8.41 to 28.29). The median TP ratio was 0.76 (interquartile range: 0.65 to 0.80). AHI was positively correlated with the TP ratio. The clinical tonsil size did not correlate with the AHI or the TP ratio. Using a TP ratio of 0.479, the sensitivity and specificity in predicting cases with moderate/severe OSA (AHI >10) were 95.8% and 81.8% respectively, while the positive and negative predictive values were 92.0% and 90.0% respectively. Conclusions: Results show that in a population of children with OSA, tonsillar hypertrophy as assessed by lateral neck radiograph correlates positively with the severity of obstructive sleep apnoea. The TP ratio has high sensitivity and specificity in predicting those with moderate/severe disease and this feature may be used as a clinical screening method in prioritising patients with OSA for further assessment.