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Asthma is the most common chronic disease of South African children, affecting 10-20% of the population. Correct treatment of chronic asthma with regular antiinflammatory controller therapy prevents symptoms, asthma exacerbations, hospitalisation and mortality. Modern treatment of asthma focuses on an assessment of asthma control in order to enable the child to lead a normal life by: • Growing and developing normally • Attending school regularly • Sleeping well at night • Participating in sport and activities • Staying out of hospital. With good controller treatment, less acute attacks of severe asthma will take place. However, to ensure fewer hospitalisations and less mortality, optimal treatment of acute attacks by families and health care professionals is critical.

To cite this article: Zollner EW, Lombard C, Galal U, Hough S, Irusen E, Weinberg E. Hypothalamic–pituitary–adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test? Pediatr Allergy Immunol 2011; 22: 614–620. Abstract Background: Hypothalamic–pituitary–adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test. Objective: To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children. Methods: Twenty-six asthmatic children, 5–18 yr old, on ICS ± NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was >83 nmol/l. HPAS was diagnosed if the ACTH failed to rise >100 pg/ml after metyrapone. Spearman correlation coefficients (r) were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated. Results: All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r = 0.68; p

The prevalence of asthma and allergic disease in children has been increasing in developed countries, but there is little information on these trends in Africa. The aim of this study was to assess time trends in the symptoms of asthma, allergic rhinitis, and atopic eczema among South African adolescents. The study was carried out by comparing cross-sectional data from two International Study of Asthma and Allergies in Childhood (ISAAC phase I and phase III) questionnaire based surveys conducted 7 yr apart of self-reported symptoms in 13- to 14-yr-old adolescents. In both surveys, schools in the same geographical area in Cape Town, South Africa, were randomly selected. A school-based sample of 5178 (in 1995) and 5037 (in 2002) pupils participated. The 12-month prevalence of wheezing (16% vs. 20.3%), exercise-induced wheeze (21.5% vs. 32.5%), nocturnal cough (23.6% vs. 36.6%), sleep disturbance due to wheeze (9.6% vs. 16%), or severe wheeze (5.1% vs. 7.8%) increased significantly, as measured by the written questionnaire. A rise in asthma symptoms was confirmed by the video questionnaire responses, in which the 12-month prevalence of wheezing (6.5% vs.11.2%), exercise-induced wheeze (11.5% vs. 13.9%), nocturnal wheeze (3.9% vs. 5.3%), nocturnal cough (11.6% vs. 19.2%), or severe wheeze (5% vs. 7%) also increased significantly. There was a small increase in the percentage of children diagnosed with asthma from 1995 to 2002 (13.1% vs. 14.4%), this was not significant. The 12-month prevalence of symptoms of allergic rhinitis (30.4% vs. 38.5%), rhinoconjunctivitis (17.6% vs. 24.3%) and eczema (11.8% vs. 19.4%) also increased significantly. An increase in the prevalence of allergic symptoms occurred in girls and boys. Limitation of daily activity from nasal symptoms (22.3% vs. 37.8%) and sleep disturbance because of eczema (8.4% vs. 15.7%) increasingly affected quality of life on the quality of life. Symptoms of asthma, allergic rhinitis and atopic eczema in adolescents have increased over the past 7 yr in this geographical area. Allergic diseases are common in this group of adolescents and increasingly impair their quality of life.

Max Klein (1941–2015) died suddenly on 27 January 2015 while riding his bicycle in the beautiful surroundings of Stellenbosch near Cape Town. Professor Klein made a large contribution to the development of paediatric critical care and paediatric pulmonology in South Africa and beyond. Max was born in the isolated central Karoo village of Calvinia where the lonely surroundings and stark landscape he experienced in his early years influenced his great strength of character. This may also account in part for his renowned powers of observation and his ability to improvise and solve problems in ingenious ways. At an early stage of his life, Max was sent to boarding school in Cape Town. He had very few happy memories of his school career. After leaving school, he studied medicine at the University of Cape Town and early on began to show the first signs of his future promise. While still a medical student, he was invited to work in the heart research laboratory of the great heart transplant pioneer Chris Barnard. This was an experience that he greatly enjoyed, and he always took great pride in the fact that his first published research paper was coauthored with Chris Barnard. Early in his career (1966–1969) he was appointed as a Wellcome Research Fellow in the first South African neonatal intensive care unit (ICU) at Groote Schuur Hospital, where he learnt mechanical …

Wheezing in young children is problematic for most practitioners. Difficulties arise in both the diagnosis and management of this clinical phenotype. Not all preschool children who wheeze have asthma. Therefore, we suggest that the “Ten Commandments” of managing preschool wheezing include thinking that in very young infants (< 1 year) wheezing is likely to be viral in origin; realising that allergy testing is mandatory to diagnose the cause of early wheezing; taking a history of asthma and allergy in family members; noting that chronic coughing is a pointer to asthma; using the term “asthma” if thatis the diagnosis; ensuring that the environmental avoidance of triggers is addressed; using a short course of montelukast for virus-induced wheezing episodes; avoiding steroids to treat virus-induced wheezing; treating associated nasal symptoms; and making sure that the follow-up of children addresses the issue of stopping therapy if it is not working.

Inhaled therapy using a metered-dose inhaler (MDI) with attached spacer has been increasingly recognized as the optimal method for delivering asthma medication for acute attacks and chronic prophylaxis. However, in developing countries the cost and availability of commercially produced spacers limit the use of MDI-spacer delivery systems. A 500-ml plastic bottle has been recently adapted to function as a spacer. This article reviews the current data on the efficacy of this bottle-spacer and discusses its advantages and limitations. It is concluded that a modified 500-ml plastic bottle is an effective spacer; modification and use of this device should be incorporated into international guidelines for the management of children with asthma.

This study used the international study of asthma and allergies in childhood (ISAAC) to investigate the association between asthma and socioeconomic deprivation among young adolescents in Cape Town, South Africa. The completed ISAAC written and video questionnaires of 4,706 13–14-yr-old school pupils were used. The prevalence of asthma symptoms was analysed by a local index of socioeconomic deprivation, based on residential location and defined on a 10-category scale from least to most deprived. Linear trends were examined visually and the prevalence odds ratio was used to summarize overall trends. In general, the least socioeconomically deprived pupils reported higher prevalences of asthma symptoms “ever” and “in the last 12 months”. In contrast, the most socioeconomically deprived pupils reported higher asthma-symptom occurrence monthly or more frequently in the previous 12 months. A subgroup of pupils from low-income areas commuting to better-off schools showed the highest symptom prevalences. The findings are consistent with a model in which an increase in the incidence of asthma is driven by factors associated with improved social circumstances, whereas severity is determined by factors associated with poverty. The impact of social mobility on asthma, including reporting of symptoms, deserves closer study. This study was supported by grants from the South African Medical Research Council and from Boehringer Pharmaceuticals.

Asthma is the most common chronic disease of South African children, affecting 10-20% of the population. It is sometimes difficult to diagnose. Where uncertainty exists, it may be more beneficial to treat the child as asthmatic, and then wean him or her off the medication later once it is under control, than neglect to administer the correct therapy to a true asthmatic. The treatment of asthma is often problematic, not because of lack of access to appropriate medication, but because of the central role played by additional factors, such as patient adherence and administration of medication technique. It is always necessary to treat the child as an individual, but some measures apply in all cases. It is important to allay anxiety about the diagnosis. This is best done by carefully explaining the nature and causes of asthma, what to do if an attack occurs, why medicines are prescribed, and how they are given. Patients must be able to understand the difference between controller and reliever therapy. The importance of regularly using controller medication needs to be emphasised. Time spent on the initial explanation and educating the parents and the child is always well rewarded by the response to treatment. Regular follow-up of these children, preferably by the same doctor, is very important.

Childhood asthma is characterised by episodes of wheezing and coughing, particularly at night. The cough is typically non-productive of sputum and is irritating and persistent. It is most troublesome in the early hours of the morning, especially between 1-2 am. Chronic cough may be a presenting symptom in young children. Wheezing, chest tightness, and shortness of breath become more obvious in children older than three years. Acute exacerbations of asthma are frequently associated with viral upper respiratory tract infections, but may also be triggered by exercise, particularly in cold and dry weather, laughter, crying, and exposure to allergens and irritants such as petrol or paint fumes. There may be a seasonal variation in symptoms, and it is common to find a diurnal variation with waking in the early hours of the morning, and increased symptoms on getting out of bed.

Background: The hypothesis that in atopic diseases the T-helper response is skewed toward a T H 2-type cytokine response was based on studies with mitogen stimulation, T-cell clones, or both. Objective: Using primary cultures, we investigated (1) whether atopic asthmatic patients have a T H 2 response and nonatopic subjects have a T H 1 response to allergen and (2) whether atopic patients have a decreased ability to mount T H 1 immune responses to mycobacterial antigens. Methods: The responses of PBMCs to allergen (house dust mite [HDM]) or purified protein derivative of Mycobacterium tuberculosis (PPD) stimulation from 10 severely and 14 moderately asthmatic patients (all allergic to HDM) were compared with those of 17 nonatopic healthy black (Xhosa) children. Results: HDM-stimulated proliferation, IL-5 release, and the IL-5/IFN-γ ratio were significantly increased in subjects with atopic asthma, whereas IFN-γ release was not significantly different. IL-4 levels were below the level of detection. PPD-stimulated proliferation, IL-5 release, IFN-γ release, and the IL-5/IFN-γ ratio were not significantly different among the groups. Each group had a significantly higher IL-5/IFN-γ ratio in response to HDM than to PPD (a T H 1 stimulus). Conclusion: Our study, which used primary cultures to investigate the hypothesis that nonatopic subjects have a T H 1 response to allergens, indicates that HDM stimulates a T H 2 cytokine response in both atopic and nonatopic subjects but that the response is enhanced in atopic patients. Our results with PPD suggest that normal and atopic asthmatic subjects can have a T H 1 cytokine response to mycobacteria, but there is a subgroup of atopic subjects that have a T H 2 response. (J Allergy Clin Immunol 2000;106:84-91.)

The study objective was to assess whether asthmatic adolescents who were regular users of inhaled corticosteroids preferred treatment with zafirlukast tablets or inhaled beclomethasone dipropionate (BDP), and, secondarily, to assess adolescents' inhaler technique and their opinions about treatment. An open-label, randomized, two-period, crossover study was conducted in 18 centres (primary care to specialist asthma centres) in South Africa, the UK, Finland and the Czech Republic. One hundred and thirty-two adolescents aged 12-17 years with asthma for at least 1 year and FEV1 > or = 75% of predicted, treated with short-acting bronchodilators and inhaled corticosteroids, entered the study. Patients received oral zafirlukast tablets (Accolate) 20 mg b.i.d. or inhaled BDP 100 or 200 microg b.i.d., provided by a standard pressurized metered-dose inhaler, for 4 weeks each. One questionnaire was used to determine preference (the primary outcome measure) and a second questionnaire was used to determine patients' likes and dislikes of treatment. Investigators also scored inhaler technique. Of 113 adolescents, 79 (70%) preferred zafirlukast compared with 31 (27%) who preferred the BDP inhaler (p < 0.001); three had no preference. Only 35 (29%) of 122 adolescents could use their inhaler correctly at study entry. Seventy-six patients (65%) rated zafirlukast tablets as 'very easy' to use, compared with 35 (30%) for the BDP inhaler. Both treatments were well-tolerated. This study shows that asthmatic adolescents prefer zafirlukast tablets by a ratio of 2.6:1 over inhaled BDP, and these results may have implications for improving adolescent patient compliance with asthma therapy.

A metered-dose inhaler (MDI) with spacer is the best way to deliver bronchodilator therapy for treatment of acute asthma. In developing countries, commercially produced spacers are generally unavailable or too costly. We tested the efficacy of home-made spacers (500 mL plastic bottle, polystyrene cup) compared with a conventional spacer for delivery of a beta2 agonist via MDI for children with acute asthma.We studied children aged 5 to 13 years with acute asthma, stratified into those with mild airways obstruction (peak expiratory flow [PEF] 60-79% of predicted value) or moderate to severe airways obstruction (PEF 20-59% of predicted value). A beta2 agonist (fenoterol hydrobromide) was given via MDI and one of four randomly assigned spacers (conventional spacer, sealed 500 mL plastic bottle, unsealed 500 mL bottle, 200 mL polystyrene cup). Clinical score, pulmonary function tests, and oximetry were recorded at baseline and 15 min after treatment. If a second bronchodilator treatment was needed, nebulised fenoterol was given and the assessment repeated 15 min later. Primary outcome measures were changes in clinical score and pulmonary function, and need for and response to nebulisation.88 children were eligible for study. In 44 children with moderate to severe airways obstruction, a cup gave significantly less bronchodilation (median increase in: forced expiratory volume in 1 s [FEV1] 0%; PEF 12%) compared with the conventional spacer (37%; 59%), sealed bottle (33%; 36%), or unsealed bottle (18%; 21%, p0.05 for difference between groups). Nebulisation was required by ten of 11 who had used a cup, nine of 11 who had used an unsealed bottle, eight of 11 who had used a sealed bottle, and only four of 11 who had used a conventional spacer. After nebulisation, improvement in FEV1 (15.5%) and PEF (26%) was more marked in children who had used a cup than in those who had used a conventional spacer (5.5% FEV1; 4% PEF), sealed bottle (3%; 0%), or unsealed bottle (7%; 9%). For 44 children with mild airways obstruction, response to bronchodilator was similar for all spacers and need for nebulisation was not associated with use of a particular spacer.A conventional spacer and sealed 500 mL plastic bottle produced similar bronchodilation, an unsealed bottle gave intermediate improvement in lung function, and a polystyrene cup was least effective as a spacer for children with moderate to severe airways obstruction. Use of bottle spacers should be incorporated into guidelines for asthma management in developing countries.

Objective To determine which parameter is the most useful screening test for hypothalamic–pituitary–adrenal suppression in asthmatic children. Design Cross-sectional study. Setting Paediatric allergy clinics in Cape Town, South Africa. Participants 143 asthmatic children of mostly mixed ancestry, aged 5–12 years. Outcome measures Primary outcome measures included Spearman correlation coefficients (r) calculated between the postmetyrapone (PMTP) serum adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11DOC), 11DOC+ cortisol (C) and height, weight, height velocity, weight velocity, change in systolic blood pressure from supine to standing, early morning urinary free cortisol (UFC), morning C, ACTH and dehydroepiandrosterone sulfate (DHEAS). Secondary outcome measures were the receiver operating characteristics (ROC) curve and the diagnostic statistics for the most promising test. Results All screening variables were weakly correlated with the three PMTP outcomes. Only DHEAS and UFC (nmol/m 2 ) were statistically significant—DHEAS for PMTP ACTH and 11DOC (r=0.20, p=0.025 and r=0.21, p=0.017); UFC (nmol/m 2 ) for PMTP 11DOC and 11DOC+C (r=0.19, p=0.033 and r=0.20, p=0.022). The area under ROC curve for DHEAS in the 5-year to 9-year age group was 0.69 (95% CI 0.47 to 0.92). At DHEAS cut-off of 0.2 µmol/L: sensitivity=0.88 (CI 0.47 to 1.00), specificity=0.61 (CI 0.42 to 0.78), positive predictive value=0.37 (CI 0.16 to 0.62), negative predictive value=0.95 (CI 0.75 to 1.00), accuracy=0.67 (CI 0.50 to 0.81), positive likelihood ratio=2.26 (CI 1.35 to 3.78), negative likelihood ratio=0.20 (CI 0.03 to 1.30). Conclusions No parameter is useful as a universal screening test. DHEAS may be suitable to exclude HPAS before adrenarche. Further research is needed to confirm these findings and identify factors, for example, genetic that may predict or protect against HPAS.

Summary Background Measurement of markers of eosinophil activation in asthmatics provides information indicative of ongoing inflammatory processes in the airways. Objectives This study was eonducted to determine the correlations between serum markers of allergie inflammation with spirometry parameters in asthmatic children in different treatment groups. Methods Blood eosinophils. serum levels of eosinophil cationic protein (ECP). eosinophil protein X (EPX), myeloperoxidase (MPO) and tryptase were measured simultaneously with serial measurements of FEV1/FVC, FEF25–75 and FEF in 60 children with acute asthma on admission and after 2, 14, 30 and 60 days. Group A received bronchodilators only (n= 20). group B received sodium cromoglycate (SCG) (n= 20) and group C received oral and/or inhaled corticosteroids (n= 20). Results Oral steroid treatment (2 mg /kg/day). given at the onset of the asthma attack, resulted in significant reduction in the ECP and EPX levels in all the children. However, these reduced ECP and EPX levels were not sustained in the children, even in those who continued on maintenance steroid treatment. Significant, but inconsistent, correlations between ECP, EPX with total eosinophil count, percentage eosinophils and spirometry parameters were observed at the different time-points. Tryptase levels were normal in all subjects. There were no significant correlations between myeloperoxidase levels and the spirometry parameters or eosinophil parameters. Serial monitoring of ECP and EPX levels was found to be of some use in predicting clinical outcome in certain steroid-dependent asthmatics (group C) but of no value in the mild asthmatics (group A). Conclusion While elevation of ECP, EPX and MPO in the serum of childhood asthmatics suggests ongoing inflammation and may inversely correlate with spirometry parameters in some patients, the relationship between these markers and airway function is not a simple one.

BACKGROUND AND OBJECTIVE: Hypothalamic-pituitary-adrenal axis suppression (HPAS) when treating children with corticosteroids is thought to be rare. Our objective was to determine the prevalence of and predictive factors for various degrees of HPAS. METHODS: Clinical features of HPAS, doses, adherence, asthma score, and lung functions were recorded in 143 asthmatic children. The overnight metyrapone test was performed if morning cortisol was >83 nmol/L. Spearman correlations coefficients ( r ) were calculated between 3 postmetyrapone outcomes and each continuous variable. A multiple linear regression model of √postmetyrapone adrenocorticotropic hormone (ACTH) and a logistic regression model for HPAS were developed. RESULTS: Hypocortisolemia was seen in 6.1% (1.8–10.5), hypothalamic-pituitary suppression (HPS) in 22.2% (14.5–29.9), adrenal suppression in 32.3% (23.7–40.9), HPAS in 16.3% (9.3–23.3), and any hypothalamic-pituitary-adrenal axis dysfunction in 65.1% (56.5–72.9). Log daily nasal steroid (NS) dose/m2 was associated with HPAS in the logistic regression model (odds ratio = 3.7 [95% confidence interval: 1.1–13.6]). Daily inhaled corticosteroids (ICSs) + NS dose/m2 predicted HPAS in the univariate logistic regression model ( P = .038). Forced expiratory volume in 1 second/forced vital capacity

Background: Hypothalamic pituitary adrenal axis suppression (HPAS) when treating asthmatic children with inhaled corticosteroids (ICS) is thought to be rare. Objective: To determine the prevalence of HPAS in asthmatic children treated with ICS and nasal steroids (NS). Methods: Twenty-six asthmatic children were recruited. Clinical features of HPAS, height, weight, height and weight velocity, steroid dose, adherence, symptom control and lung functions were documented. Metyrapone test was performed if the serum cortisol was > 83 nmol/L ( > 3 µ g/dL). Results: No child had a serum cortisol < 83 nmol/L ( < 3 µ g/dL). Prevalence of HPAS was 35 (CI = 17 % – 56 % ). Daily NS dose/ m 2 and cumulative NS dose/m 2 were signifi cantly (p = 0.03) inversely correlated with the post-metyrapone ACTH (r = – 0.42 for both). Current ICS dose was not associated with the post-metyrapone ACTH (r = 0). There was a weak correlation with the daily ICS dose/m 2 (r = – 0.12) and cumulative ICS dose/m 2 (r = – 0.26). Conclusions: A third of asthmatic children on ICS and NS develop HPAS. Contributing factors are the use of NS, body size and cumulative dose of ICS.

Hypothalamic-pituitary-adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test.To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children.Twenty-six asthmatic children, 5-18 yr old, on ICS ± NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was83 nmol/l. HPAS was diagnosed if the ACTH failed to rise100 pg/ml after metyrapone. Spearman correlation coefficients (r) were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated.All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r = 0.68; p0.001). The best discrimination between those who have and those who do not have HPAS is a morning serum ACTH level of 11.7 pg/ml. This corresponds to a sensitivity of 0.89 (0.57-0.98), a specificity of 0.77 (0.53-0.90), a positive predictive value of 0.67 (0.39-0.87), a negative predictive value of 0.93 (0.69-0.99), an accuracy of 0.81 (0.61-0.94), a positive likelihood ratio of 3.78 (1.68-9.49) and a negative likelihood ratio of 0.15 (0.03-0.60).The morning serum ACTH level was found to be the most useful screening test to detect HPAS in this sample of children receiving ICS ± NS. A larger study should be undertaken to refine the diagnostic precision of the morning serum ACTH level.

This study was conducted to confirm cefadroxil's antimicrobial efficacy and the in vitro indications that this drug may have an immunoglobulin E (IgE)-related immunomodulatory effect. Thirty-three patients ages 6 months to 12 years suffering from Staphylococcus aureus superinfected atopic dermatitis and having elevated serum IgE levels were randomized to receive either cefadroxil 50 mg/kg/day in two equal doses or placebo for 2 weeks. All patients treated with cefadroxil showed complete clinical resolution of the superinfection, compared with only 40% of the placebo group (P < 0.0001). Only one resistant isolate was identified. Although there were strong within-group improvements in the allergy-related signs and symptoms, no differences in atopic symptom improvement were seen between the treatment groups. The IgE levels did not change appreciably. These results suggest that, from an antibacterial viewpoint, cefadroxil is a useful adjunct in the treatment of superinfected atopic dermatitis when S aureus is involved.

The predictive value of raised cord blood (CB) total eosinophil counts (TEC) with regard to atopic sensitisation was studied prospectively for 1 year in 53 Black, 52 White and 57 Mixed full-term newborns. The maternal TEC, in relation to the stress of labour, were also studied. Ethnic differences in the CB TEC were shown between the Black/White (p = 0.03) and the White/Mixed (p = 0.05) groups. The newborns sex, anatopic family history (aFH) and the method of birth had no influence on the CB TEC in any ethnic group. There were no unequivocal differences in CB TEC between those newborns who became atopic during infancy and those who did not in any of the ethnic groups, although in the Black infants, there was a marginal trend towards significance (p = 0.05). Raised CB TEC values do not, therefore, seem to be an inherited factor in terms of a predisposition for atopic disease.

Background: Inhaled bronchodilator treatment given via a metered dose inhaler (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional spacers are expensive or unavailable in developing countries, but there is little information on the efficacy of low-cost spacers in young children. Objective: To compare the response to bronchodilator treatment given via a conventional or a low-cost bottle spacer Methods: A randomised controlled trial of the efficacy of a conventional spacer compared with a bottle spacer for bronchodilator treatment in young children with acute lower airway obstruction. Bronchodilator treatment was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and oximetry recording were carried out before and after 15 min of treatment. MDI–spacer treatment was repeated up to three times, depending on clinical response, after which nebulisation was used. The primary outcome was hospitalisation. Results: 400 children, aged (median (25th–75th centile)) 12 (6–25) months, were enrolled. The number of children hospitalised (n = 60, 15%) was identical in the conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes including change in clinical score (−2 (−3 to −1)), oxygen saturation (0 (−1 to 1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a similar number in the conventional (37 (18.5%)) and bottle spacer groups (41 (20.5%)). Conclusion: A low-cost bottle spacer is as effective as a conventional spacer for bronchodilator treatment in young children with acute obstruction of the lower airways.

Chronic urticaria (CU) in childhood remains a challenge for investigation, and its etiology is largely unknown. Autoantibodies to the high-affinity IgE receptor (FcepsilonRI) are believed to play a role in the pathogenesis of this disease in adults.To determine the prevalence of autoantibodies to FcepsilonRIalpha on basophils in children with CU vs atopic eczema dermatitis syndrome (AEDS).Eighty children with CU were compared with 38 children with AEDS. In addition to complete blood cell counts and total IgE measurements, CAP-RASTs to egg, codfish, soy, milk, and peanut were performed. Stool samples were examined for parasites, and autologous serum skin testing and a functional anti-FcepsilonRIalpha assay were conducted to detect autoantibodies.No significant differences were observed between children with CU and controls in mean basophil or eosinophil counts. Twenty (26%) of 77 children with CU and 31 (82%) of 38 with AEDS had positive CAP-RAST results (P.001). Only 2.5% of the children with CU and 0% with AEDS had stool samples positive for parasites (P = .005). Anti-FcepsilonRIalpha autoantibodies were positive in 37 (47%) of 78 children with CU and in none of 33 with AEDS. Non-IgG histamine-releasing factors were found in 10 (13%) of 78 children with CU.Children have a similar prevalence of autoantibodies to the FcepsilonRIalpha as has been previously published for adults. Few have type I allergies, and parasite infestation is also uncommon. Further studies are required to investigate the predictive value of the autoantibodies in these children with respect to clinical profile, requirements for medications other than antihistamines, and remission rates.

Spina bifida children have a high prevalence of latex allergy in studies reported from Europe and the USA. This study investigated the prevalence of latex allergy in a cohort of 24 spina bifida children at the Red Cross Children's Hospital from Cape Town, South Africa. The children were investigated using a detailed questionnaire, skin prick tests (ALK-Abello), ImmunoCap RASTs, Western blotting and ELISA, using the purified latex proteins Hev b1 and Hev b3 and whole latex preparation. A low overall prevalence of latex sensitization of 16.7% was found in the children. Children who were sensitive reacted to water insoluble to Hev b1 and Hev b3 proteins. The low prevalence of latex sensitization in the South African children may not be entirely explained by stringent latex avoidance. The children were from a low socioeconomic social status and ‘hygiene’ and other factors should be considered.

Environmental factors are known to influence the development of allergic rhinitis and atopic eczema in genetically susceptible individuals. Socioeconomic status (SES) may be an important indicator of risk for these conditions. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase 1 written questionnaire was used to determine the prevalence and severity of allergic rhinoconjunctivitis and atopic eczema symptoms in 4947 pupils aged 13-14 years attending 30 schools in socioeconomically diverse areas of Cape Town. Home addresses were used to stratify participants into five SES bands. Relationships between symptom prevalence and severity, and SES, recent urbanization and upward socioeconomic mobility were examined. Logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (CI) in order to assess overall trends by SES. The prevalences of self-reported allergic rhinitis symptoms and recurrent itchy rash in the past year were 33.2% and 11.9% respectively. Girls had a significantly higher prevalence of all symptoms than boys. The prevalence of allergic rhinitis symptoms increased from lowest to highest SES (overall OR for rhinitis symptoms in past year = 1.16, 95% CI 1.11-1.21). There was no significant trend in reported eczema symptoms by SES other than for the question, 'Have you ever had eczema' (OR = 0.88, 95% CI 0.83-0.93). Longer period of urbanization was weakly associated only with recurrent itchy skin rash (OR = 1.05, 95% CI 1.01-1.09). 'Socially mobile' pupils, i.e. those resident in the lowest SES areas but attending highest SES schools showed significantly higher prevalences of eczema and some rhinitis symptoms than pupils attending lowest SES schools. These findings may reflect differences in reporting related to language, culture and access to medical care rather than real differences in prevalence.

This study investigated whether household environmental tobacco smoke (ETS) exposure is associated with increased bronchial hyperresponsiveness (BHR) in children with asthma. Two hundred forty-nine children, ages 7-11 years, sampled from a larger group with reported asthma or multiple asthma symptoms identified in a community survey in Cape Town, underwent histamine challenge testing and had urinary cotinine measured. Parents were interviewed for information on smoking habits and a variety of covariates. Children with asthma whose mothers smoked had a lower frequency of BHR than asthmatic children of nonsmoking mothers, particularly if the mother smoked > or = 15 cigarettes daily. BHR was also less common among children sharing a house with four or more smokers vs. fewer or none. BHR was unrelated to paternal smoking. In contrast, FEV1 was lower among children whose mothers currently smoked. The findings do not support a mechanism whereby ETS exposure aggravates existing childhood asthma by increasing BHR. This association may be masked, however, by the degree to which mothers of asthmatic children adjust their smoking. The results are consistent with an adverse effect of maternal smoking on lung function in asthmatic children.

The increasing prevalence of childhood asthma in the developed world is a cause for concern. Much research is currently being conducted in an attempt to identify possible reasons for this occurrence. A so-called Western lifestyle has been the factor most commonly cited to explain this worrying increase in asthma prevalence. In essence, this implies a way of life where children are exposed from early infancy to a wide range of foods, infections, indoor and outdoor allergens, and irritants and to the effects of motor vehicle pollution. Until fairly recently, children in many African countries lived mainly in rural areas and were not exposed to the effects of a Western lifestyle. Early studies in a limited number of African countries showed a very low rural prevalence of childhood asthma, especially where children lived according to a traditional lifestyle. These same studies showed that asthma was not uncommon in urbanized African children. There has been an increasing tendency over the past 20 years for those in rural communities to move to the large urban centers. More recent childhood asthma prevalence studies, especially those from Kenya and Ghana, have confirmed the urban-rural differences but have shown a much narrower gap. In part this may be the result of exposure of rural children to agricultural pesticides and irritants as well as of an increasing tendency to adopt a more Westernized lifestyle such as the use of beds with mattresses, pillows, and blankets. These circumstances on the African continent provide a natural laboratory in the quest for factors that influence the development of asthma in susceptible children. Once more fully elucidated, it is possible that much valuable information will be available to combat the relentless increase in childhood asthma both here as well as in the developed world.

Background: Allergic asthma is increasing in black South Africans, a cohort with inherently high basal IgE levels. Atopy has been linked to an excess of the T helper 2 cytokines IL-4 and IL-5 relative to the T helper 1 cytokine interferon-γ (IFN-γ); however, most studies have utilized T cell clones. Studies on peripheral blood mononuclear cells (PBMC) have shown decreased IFN-γ release in patients with atopic dermatitis. It is uncertain whether this finding extends to atopic asthma. Objectives: To characterize cytokine release by mitogen-activated PBMC from Xhosa children and to investigate whether reduced IFN-γ release is a feature of atopic asthma and whether there is a relationship between cytokine profiles and asthma severity. Methods: Cytokine release and proliferation of phytohemagglutinin-stimulated PBMC from 10 patients with severe asthma and 14 patients with moderate asthma (highly allergic to house dust mites) and 17 healthy controls was assessed. Total serum, allergen-specific, and Ascaris -specific IgE was measured. Results: Proliferation did not differ between the groups. The release of IFN-γ was progressively decreased (and the IL-4/IFN-γ ratio increased) in the groups with moderate or severe asthma. Tumor necrosis factor-α release was reduced, but IL-4, IL-5, and granulocyte-macrophage–colony stimulating factor release was unchanged. The presence of Ascaris -specific IgE did not influence the cytokine profiles. Conclusion: Our study extends the findings observed for other atopic disorders and suggests that defective IFN-γ release is a generalized feature of atopic diseases. This study—the first to investigate both severe and moderate asthma, with the groups having similar atopic profiles—indicates that the extent of the defect in IFN-γ release might be related to asthma severity. (J Allergy Clin Immunol 1997;100:662-8.)

To identify modifiable risk factors for wheezing illness in childhood, the associations between current asthma or wheezing and factors such as household smoking, damp and dietary salt preference were measured in a questionnaire-based prevalence study of schoolchildren 7 to 9 yr of age in Cape Town. In a random sample of 15 schools, questionnaires were completed by parents of 1,955 children, from which 368 cases and 294 controls were selected on the basis of reported asthma diagnosis or symptoms. Urinary cotinine concentrations were measured, and the parents were interviewed. An exposure-response relationship between the urinary cotinine creatinine ratio and asthma/wheeze was observed. In multivariate analysis, predictors of asthma/wheeze were hay fever (odds ratio [OR] - 5.30; 95% confidence interval [CI] = 3.16 to 8.89), eczema (OR = 2.19; 95% CI = 1.33-3.62), parental asthma (OR = 1.77; 95% CI = 1.11 to 2.84), absence of paternal contribution to income (OR = 1.72; 95% CI = 1.17 to 2.54), maternal smoking in pregnancy (OR = 1.87; 95% CI = 1.25 to 2.81), and each additional household smoker (OR = 1.15; 95% CI = 1.01 to 1.30). Findings were similar, with higher odds ratios for most variables, except number of household smokers, when the group was restricted to children with parent-reported asthma. The findings confirm that household smoking is an important modifiable risk factor in asthma/wheeze among young schoolchildren, and they suggest that maternal smoking in pregnancy and current household exposure are independent contributors to this effect.

Rationale Allergen sensitization is an important risk factor for allergic disease, including allergic rhinitis. This study reports the sensitization status, and efficacy of fexofenadine (FEX), in a subset of children (aged 6–11 yrs) from the Southern Hemisphere with seasonal allergic rhinitis (SAR) enrolled into a large, placebo-controlled, randomized, parallel-group study. Methods For randomization, children required a positive skin prick test to at least one pollen allergen for the current season and concordance to that specific allergen in in vitro IgE testing. Specific IgEs were determined by the Fluoro Enzyme Immuno Assay; positive IgE was defined as IgE class ≥2 (>0.7 kUA/L). Analysis was performed on the modified intention-to-treat (mITT) population, treated with either FEX HCl 30 mg BID or placebo. Efficacy was evaluated as the overall mean change from baseline in 12-hour reflective total symptom score (TSS). Results A subset of 300 subjects (FEX, n=145; placebo, n=155), from 40 centers in Argentina, Chile, Uruguay and South Africa, was analyzed. Sensitization to pollen allergens assessed by plant category showed that grasses were the most common group of allergens (>93%); sensitization to weeds was 8.9% for FEX and 17.8% for placebo; sensitization to trees was 20.5% for FEX and 20.4% for placebo. FEX significantly improved the mean change from baseline in TSS compared with placebo ( p Conclusions In this subset of children from the Southern Hemisphere, grasses were the most common groups of sensitizing allergens. Furthermore, FEX significantly improved the symptoms of SAR in this population of children.

Raised concentrations of cord blood serum (CBs) IgE have previously been demonstrated to reflect a hereditary predisposition for atopy in First World, predominantly white populations. A cross-sectional study of 53 black, 52 white, and 58 mixed race newborn infants and maternal pairs was performed in a multiethnic, mixed First and Third World society. The CBs IgE concentrations were measured with a modification of the standard IgE PRIST, which could reliably determine IgE concentrations to an accuracy of 0.01 kU/L. The black group had the highest geometric mean and median CBs IgE concentrations (0.21; 0.16 kU/L), followed by the white group (0.12; 0.12 kU/L) and the mixed group (0.10; 0.08 kU/L). If those newborn infants with an atopic family history and maternal ascariasis were excluded, the remainder had geometric mean and median CBs IgE concentrations of 0.20; 0.16 kU/L in the black subgroup, followed by values of 0.06; 0.05 kU/L in the mixed subgroup, and 0.05; 0.07 kU/L in the white subgroup. Statistically significant ethnic differences in the median CBs IgE concentrations of these subgroups were demonstrated between the black-white (p less than 0.05) and the black-mixed (p less than 0.005) ethnic groups. A positive family history of atopy influenced the CBs IgE concentrations in the white and mixed groups but not in the black group. Of those newborn infants with a CBs IgE concentration greater than 0.5 kU/L, a family history of atopy was found in 100% of the white newborn infants, in 58.3% of the mixed newborn infants, and only in 14.3% of the black newborn infants. Many of the black newborn infants without a family history of atopy had extremely high CBs IgE concentrations. The influence of maternal ascariasis was equivocal in the mixed group but of no significance in the black group. The high CBs IgE concentrations in the black newborn infants, independent of an atopic family history and maternal ascariasis, suggest that this atopic marker may therefore be of limited use in identifying the "high allergic-risk" newborn infant in black Third World populations who appear to represent a pool of genetic high IgE-responder phenotypes.

Malingering can pose a serious problem to attending medical personnel. A technique employed at the Children's Asthma Research Institute and Hospital (CARIH) in order to modify this behavioral pattern—time-out (T.O.) from positive reinforcement—is described. In addition, procedures were presented both for shaping up socially-appropriate behaviors and for insuring that gains were maintained when the subject returned home.

Serum samples from 60 adults and 64 children with atopic dermatitis were tested for antistaphylococcal IgE antibodies with RAST discs coupled to cellular proteins from Wood 46 strain S. aureus. Anti- S. aureus IgE antibodies were detected in 19 (29.6%) of the children and 14 (23.3%) of the adult patients. Anti- S. aureus IgE-positive adults had more severe and prolonged disease than those who were negative. Two groups of children comprising 10 who were anti- S. aureus IgE positive and 10 who were negative were compared. Children with anti- S. aureus IgE antibodies had more severe and more extensive disease ( p S. aureus infections ( p p p p

Forty-two chronic asthmatic children, including 10 with associated eczema, were examined for lenticular complications. The children had received oral corticosteroids for a minimum of 3 years. Twelve were treated with beclomethasone inhalant therapy, and the children with eczema had had topical corticosteroids. Only one child was found to have cataracts commensurate with corticosteroid therapy. Possible reasons for the low incidence of cataracts in this study are discussed.

Background Childhood asthma is believed to be a serious problem in Cape Town, South Africa. This study aimed to measure the prevalence and reliability of asthma symptoms and reported asthma in Cape Town schoolchildren aged mainly 7 and 8 years, and to assess underdiagnosis. Method A questionnaire was completed by parents of 1955 children, followed by 620 personal interviews repeating the questions. Results The prevalence of recent wheeze (previous 12 months) (26.8%) was high by international comparison, but not that of reported asthma (10.8%). Among children with more than 12 recent attacks of wheeze, only 60% were reported as asthmatic and 55% as receiving regular treatment. Symptom prevalences varied with the respondent's familial relationship to the child. On some questions the interview produced higher wheeze prevalences than the self-administered questionnaire. Repeatability of questions varied: asthma over (kappa = 0.69), recent wheeze (kappa = 0.59), and recent sleep disturbance by wheeze (kappa = 0.56) were the most reliable. Conclusions Prevalence based on symptom reports may vary with the respondent and between self- and interviewer-administered questionnaires. Also, certain questions currently proposed for childhood asthma questionnaires may be unreliable. Nevertheless, it can be concluded that the prevalence of wheeze is high in this population, and that underdiagnosis and undertreatment of asthma are a problem.