Young children experience little emotional burden during invasive procedures in asthma research.

Research in children should strike the right balance between protecting underage study subjects and advancing the medical field. This study gives insight into the emotional burden that common invasive research procedures in asthma research have on young children, both from the child and parent perspective. Puppetry was used to stimulate children (age 5-6 years) to explain their emotional burden prior to and after the research procedures. We operationalised emotional burden as willingness to participate in future research and reluctance towards participation. Parents filled out a questionnaire on this topic. Symptomatic patients as well as healthy controls were analysed. Forty-one children were included. Children's anticipatory fear for future research showed a clear decrease of 0.7 ± 1.6 on a 5-point Likert scale as a consequence of participation (p = 0.02). Sixty percent of all participating children explicitly indicated willingness to undergo identical research procedures again. Children uninformed by their parents about the venipuncture were significantly more reluctant to the venipuncture after the procedure (p < 0.01), compared to children who had been informed (4.0 ± 0.9 resp. 2.8 ± 1.2).Conclusion: This study suggests that the emotional burden of participation in asthma research for underage children can be prevented when they are properly informed and decreases as a consequence of participations. We believe increased emphasis should be placed on informing children and evaluating the emotional impact of research to help caretakers and research ethics committees make informed decisions about participation of children in medical research. What is Known: • Medical professionals and parents are likely to overestimate children's discomfort undergoing (invasive) research procedures. • Two thirds of children (age 6-18 years) participating in medical research indicated that they would participate in the same research study again. What is New: • Pre-school children experience little emotional burden during invasive procedures in asthma research. • Proper communication about (invasive) research procedures in pre-school children helps to reduce the anticipatory fear of these procedures in the future.

Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis.

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th) 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and CCL22 chemokines. Objective: To explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE). Subjects and methods: Serum samples (n = 41) obtained from a randomized, double-blind, and clinical dietary intervention study were used to study biomarkers in infants with AD. Baseline- and post-intervention samples (4 months) were used, six chemokines and nine ratios thereof were analyzed using Luminex and correlated to AD severity. In the initial study, the infants were randomized to receive extensively hydrolyzed whey-based formula without (control) or with short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (9:1) and Bifidobacterium breve M-16V (active). Results: 31 Infants up to 11 months of age, with an objective-SCORAD score (oSCORAD) ≥ 20 and elevated total-IgE and/or specific-IgE levels were included. In time, the median oSCORAD decreased in both groups by -8 (control, p < 0.05; active, p < 0.01). Irrespective of dietary intervention, several changes in Th2 chemokines (CCL17 and CCL22), inflammatory chemokine (CCL20), and the Th1 chemokine, CXC chemokine ligand (CXCL) 9, were detected over time. Overall CCL17 correlated to oSCORAD (r = 0.446, p < 0.01). After 4 months of dietary intervention, CXCL9 was higher (p < 0.01) in the active group compared with control [active, 2.33 (1.99-2.89); controls, 1.95 (1.77-2.43) log 10 median (range)]. In addition, a reduction in Th2/Th1 chemokine ratios for CCL17/CXCL9, CCL22/CXCL9, CCL20/CXCL10, and CCL20/CXCL11 was detected associated with the active intervention. Conclusion: While this study is small and exploratory in nature, these data contribute to immune biomarker profiling and understanding of AD in infants.

Exposure to Environmental Contaminants and Lung Function in Adolescents-Is There a Link?

Dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDF)), polychlorinated biphenyls (PCBs), and brominated flame retardants (BDEs) are well known toxic environmental contaminants. Their possible role in the incidence of respiratory disease is not yet well understood. Previous studies showed a negative effect on lung function in relation to prenatal and lactational dioxin exposure in pre-pubertal children. Effects of BDE exposure on the lung function have not previously been evaluated. As part of a longitudinal cohort study, the effects of perinatal dioxin (PCDD/F) exposure and serum PCDD/F, dl-PCB, and BDE levels on lung function in adolescents were assessed using spirometry, a body box, and diffusion measurements. Thirty-three children (born between 1986 and 1991) consented to the current follow-up study. Prenatal, lactational, and current dioxin, PCB, and BDE concentrations were determined using GC-MS. No relationship was seen between prenatal and lactational dioxin exposure, nor with current PCB body burden, and lung function. Indications of increasing airway obstruction were seen in relation to increasing current BDE exposure. This is a novel finding and certainly warrants further research.

Alterations in the programming of energy metabolism in adolescents with background exposure to dioxins, dl-PCBs and PBDEs.

OBJECTIVES: Dioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life. STUDY DESIGN: In The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987. Fasting glucose, insulin, HbA1c and leptin were analysed in 33 children of the original cohort of 60. BMI, glucose:insulin and BMI:leptin ratios were calculated. Prenatal exposure, lactational intake and current serum levels of dioxins (PCDD/F), dl-PCBs and PBDE concentrations were determined using (HR)GC-MS. RESULTS: Prenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence. Postnatal lactational PCDD/F intake was also negatively correlated to fasting insulin concentration (p = 0.028). Current serum levels of PCDD/Fs and total TEQ (dl-PCBs+PCDD/Fs) were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of PBDEs. A positive correlation between the insulin and leptin concentrations (p = 0.034) was observed. No effects were found on leptin levels, BMI:leptin ratio, HbA1c levels or BMI. DISCUSSION/CONCLUSION: This study indicates that prenatal and lactational exposure influences glucose metabolism in adolescents, presumably through a negative effect on insulin secretion by pancreatic beta cells. Additionally, the very low recent background exposure to dioxins in puberty possibly has an effect on the glucose level.

BMI predicts exercise induced bronchoconstriction in asthmatic boys.

BACKGROUND: Exercise induced bronchoconstriction (EIB) is a frustrating morbidity of asthma in children. Obesity has been associated with asthma and with more severe EIB in asthmatic children. OBJECTIVES: To quantify the effect of BMI on the risk of the occurrence of EIB in children with asthma. METHODS: Data were collected from six studies in which exercise challenge tests were performed according to international guidelines. We included 212 Children aged 7-18 years, with a pediatrician-diagnosed mild-to-moderate asthma. RESULTS: A total of 103 of 212 children (49%) had a positive exercise challenge (fall of FEV1 ≥ 13%). The severity of EIB, as measured by the maximum fall in FEV1 , was significantly greater in overweight and obese children compared to normal weight children (respectively 23.9% vs 17.9%; P = 0.045). Asthmatic children with a BMI z-score around +1 had a 2.9-fold higher risk of the prevalence of EIB compared to children with a BMI z-score around the mean (OR 2.9; 95%CI: 1.3-6.1; P < 0.01). An increase in BMI z-score of 0.1 in boys led to a 1.4-fold increased risk of EIB (OR 1.4; 95%CI: 1.0-1.9; P = 0.03). A reduction in pre-exercise FEV1 was associated with a higher risk of EIB (last quartile six times higher risk compared to highest quartile (OR 6.1 [95%CI 2.5-14.5]). CONCLUSIONS: The severity of EIB is significantly greater in children with overweight and obesity compared to non-overweight asthmatic children. Furthermore, this study shows that the BMI-z-score, even with a normal weight, is strongly associated with the incidence of EIB in asthmatic boys.

Remaining symptoms in half the children treated for milk allergy.

UNLABELLED: The aim of this study was to investigate the cumulative incidence and predictive variables of treatment failure with a whey-based extensively hydrolyzed formula (w-eHF) in children with cow's milk allergy (CMA). All children were diagnosed with CMA, using double-blind placebo-controlled food challenge (DBPCFC) with amino acid-based formula as placebo, and receive w-eHF treatment after diagnosis. Forty-nine children with CMA were included. w-eHF treatment failure was defined as incomplete resolution of original CMA symptoms upon w-eHF treatment and disappearance of these symptoms upon replacement of w-eHF with amino acid-based formula. A multiple logistic regression model was used to investigate which variables could predict treatment failure. Twenty-five (51%; 95% confidence interval (CI) 38-64%) of the children with CMA failed on w-eHF. Only "gastrointestinal discomfort" was found to contribute independently to the probability of failing w-eHF, odds ratio (95% CI) 8.994 (1.007-79.457). CONCLUSIONS: In half of the children with proven CMA, there is incomplete resolution of symptoms upon w-eHF treatment. This study needs to be repeated including DBPCFC with w-eHF to provide more definitive diagnosis, especially since gastrointestinal discomfort seems to be the sole predictive variable for treatment failure. In the meantime, a change in formula should be considered in children with incomplete symptom resolution upon w-eHF treatment.

Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze.

Preschool rhinovirus-induced wheeze is associated with an increased risk of asthma. In adult asthma, exhaled volatile organic compounds (VOC) are associated with inflammatory activity. We therefore hypothesised that acute preschool wheeze is accompanied by a differential profile of exhaled VOC, which is maintained after resolution of symptoms in those children with rhinovirus-induced wheeze. We included 178 children (mean±sd age 22±9 months) from the EUROPA cohort comparing asymptomatic and wheezing children during respiratory symptoms and after recovery. Naso- and oropharyngeal swabs were tested for rhinovirus by quantitative PCR. Breath was collected via a spacer and analysed using an electronic nose. Between-group discrimination was assessed by constructing a 1000-fold cross-validated receiver operating characteristic curve. Analyses were stratified by rhinovirus presence/absence. Wheezing children demonstrated a different VOC profile when compared with asymptomatic children (p<0.001), regardless of the presence (area under the curve (AUC) 0.77, 95% CI 0.07) or absence (AUC 0.81, 95% CI 0.05) of rhinovirus. After symptomatic recovery, discriminative accuracy was maintained in children with rhinovirus-induced wheeze (AUC 0.84, 95% CI 0.06), whereas it dropped significantly in infants with non-rhinovirus-induced wheeze (AUC 0.67, 95% CI 0.06). Exhaled molecular profiles differ between preschool children with and without acute respiratory wheeze. This appears to be sustained in children with rhinovirus-induced wheeze after resolution of symptoms. Therefore, exhaled VOC may qualify as candidate biomarkers for early signs of asthma.

Inpatient treatment of children and adolescents with severe obesity in the Netherlands: a randomized clinical trial.

IMPORTANCE: Severe childhood obesity has become a major health problem, and effective, evidence-based interventions are needed. The relative effectiveness of inpatient compared with ambulatory treatment remains unknown. OBJECTIVE: To determine whether an inpatient treatment program is more effective than an ambulatory treatment program at achieving a sustained weight loss in children and adolescents with severe obesity. DESIGN, SETTING, AND PARTICIPANTS: We conducted a randomized clinical trial with a 2-year follow-up at a tertiary referral center for pediatric obesity in the Netherlands. We recruited 90 children and adolescents aged 8 to 18 years with severe obesity (body mass index [BMI] z score, ≥3.0 or >2.3 with obesity-related health problems). INTERVENTIONS: Patients were randomly assigned to an inpatient (6 months of hospitalization on working days) or an ambulatory (12 days of hospital visits at increasing intervals during a 6-month period) treatment program. Both treatment programs involved an intensive, family-based, lifestyle intervention, including exercise, nutritional education, and behavior modification for the patients and their caregiver(s). MAIN OUTCOMES AND MEASURES: Change in BMI z score. Secondary outcomes included fasting insulin, fasting plasma glucose, 2-hour plasma glucose, and lipid levels, insulin sensitivity, liver function test results, waist circumference, blood pressure, body composition, and aerobic fitness (peak oxygen consumption, Vo2). Outcomes were analyzed by intention to treat. RESULTS: Immediately after treatment, reductions in the BMI z score were significantly larger for the inpatient than the ambulatory groups (mean [SE] difference, -0.26 [0.12; 95% CI, -0.59 to -0.01]; P = .04). Change from baseline for the BMI z score in the inpatient group was -18.0% (P = .001) immediately after treatment, -8.5% (P = .008) at 18 months, and -6.3% (P = .38) at 30 months; in the ambulatory group, changes from baseline were -10.5% (P = .001), -6.2% (P = .39), and -1.5% (P > .99), respectively. The favorable outcomes of the inpatient group could not be sustained at 12 and 24 months after treatment. In addition, significant differences in favor of the inpatient group immediately after treatment were found for levels of fasting insulin (-6.37 IU/L; P = .02), total cholesterol (-19.51 mg/dL; P = .01), low-density lipoprotein cholesterol (-13.48 mg/dL; P = .03), and triglycerides (-25.39 mg/dL; P = .01), and insulin sensitivity (-1.37; P = .02), fat mass (-3.31%; P = .03), and peak Vo2 (378.2 mL/min; P = .01). CONCLUSIONS AND RELEVANCE: In severely obese children and adolescents, inpatient treatment was superior to ambulatory treatment immediately after treatment, but effects were not sustained at long-term follow-up. These findings stress the need to further study maintenance strategies for sustainable weight loss. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1172.

Predicting asthma in preschool children at high risk presenting in primary care: development of a clinical asthma prediction score.

BACKGROUND: A setting-specific asthma prediction score for preschool children with wheezing and/or dyspnoea presenting in primary healthcare is needed since existing indices are mainly based on general populations. AIMS: To find an optimally informative yet practical set of predictors for the prediction of asthma in preschool children at high risk who present in primary healthcare. METHODS: A total of 771 Dutch preschool children at high risk of asthma were followed prospectively until the age of six years. Data on asthma symptoms and environmental conditions were obtained using validated questionnaires and specific IgE was measured. At the age of six years the presence of asthma was assessed based on asthma symptoms, medication, and bronchial hyper-responsiveness. A clinical asthma prediction score (CAPS) was developed using bootstrapped multivariable regression methods. RESULTS: In all, 438 children (56.8%) completed the study; the asthma prevalence at six years was 42.7%. Five parameters optimally predicted asthma: age, family history of asthma or allergy, wheezing-induced sleep disturbances, wheezing in the absence of common colds, and specific IgE. CAPS scores range from 0 to 11 points; scores <3 signified a negative predictive value of 78.4% while scores of >7 signified a positive predictive value of 74.3%. CONCLUSIONS: We have developed an easy-to-use CAPS for preschool children with symptoms suggesting asthma who present in primary healthcare. After suitable validation, the CAPS may assist in guiding shared decision-making to tailor the need for medical or non-medical interventions. External validation of the CAPS is needed.

Problematic severe asthma in children treated at high altitude: tapering the dose while improving control.

BACKGROUND: Multidisciplinary treatment at high altitude is a possible treatment option for problematic severe asthma (PSA) in children. This management can result in the tapering of inhaled corticosteroids. AIM: Our aim was to analyze the effect of multidisciplinary treatment at high altitude, notably the ability to taper corticosteroids. To get an insight into possible factors influencing tapering, we examined whether demographic variables, disease control and quality of life at treatment entrance could predict the tapering of corticosteroids. METHODS: This prospective open-phase cohort study analyzed the data of 43 children aged 8-17 years referred to a specialized high altitude treatment centre. Lung function (FEV1, FEV1/VC), inflammation (FeNO), medication level, asthma control (ACT) and quality of life [PAQLQ(S)] were evaluated on admission and at discharge. RESULTS: Thirty-two (74%) children fulfilled PSA criteria. Three (7%) children used daily oral steroids. After 72 ± 30 (mean ± SD) days of treatment, the mean dosage of inhaled corticosteroids (ICS) could be significantly reduced from 1315 µg ± 666 budesonide equivalent to 1132 µg ± 514. Oral steroid maintenance therapy could be stopped in all patients. FeNO, asthma control and quality of life improved (p < 0.001) from admission to discharge; FEV1 was in the normal range on both occasions. Apart from ICS levels at entrance, multiple regression analyses did not show any associated factor predicting the reduction of ICS dosage during treatment. CONCLUSION: The results indicate that high altitude treatment may be a treatment option for children with PSA, but it is not possible to predict ICS tapering off from health status variables at treatment entrance.

Abusive head trauma in young children in the Netherlands: evidence for multiple incidents of abuse.

AIM: We investigated the prevalence of risk factors for and the prevalence of prior abuse in abusive head trauma victims in the Netherlands. METHODS: We performed a retrospective file review of all abusive head trauma cases in the Netherlands in which forensic medical expertise was requested by the courts, between 2005 and 2010. Outcome measures were risk factors and indicators for prior abuse. RESULTS: Eighty-nine cases were included; 62% boys, median age 3.5 months. Impact trauma was found in 48% of cases, with a male perpetrator in 79%. Prematurity, dysmaturity and twins/triplets were found in 27%, 23% and 10% of cases, respectively, maternal age under 20 years in 17%. Of the parents, 60% had completed only primary or secondary education, 38% of the families were known to child welfare authorities. There was evidence for prior abuse in 81% of the cases. CONCLUSION: The high number of families with prior abuse indicates that both the healthcare system and child welfare authorities failed to protect some of the children that have been in their care. Our results highlight the importance of training healthcare and child welfare professionals in recognizing physical abuse, as well as the importance of optimizing abusive head trauma prevention strategies.

Nurse versus physician-led care for the management of asthma.

BACKGROUND: Asthma is the most common chronic disease in childhood and prevalence is also high in adulthood, thereby placing a considerable burden on healthcare resources. Therefore, effective asthma management is important to reduce morbidity and to optimise utilisation of healthcare facilities. OBJECTIVES: To review the effectiveness of nurse-led asthma care provided by a specialised asthma nurse, a nurse practitioner, a physician assistant or an otherwise specifically trained nursing professional, working relatively independently from a physician, compared to traditional care provided by a physician. Our scope included all outpatient care for asthma, both in primary care and in hospital settings. SEARCH METHODS: We carried out a comprehensive search of databases including The Cochrane Library, MEDLINE and EMBASE to identify trials up to August 2012. Bibliographies of relevant papers were searched, and handsearching of relevant publications was undertaken to identify additional trials. SELECTION CRITERIA: Randomised controlled trials comparing nurse-led care versus physician-led care in asthma for the same aspect of asthma care. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Five studies on 588 adults and children were included concerning nurse-led care versus physician-led care. One study included 154 patients with uncontrolled asthma, while the other four studies including 434 patients with controlled or partly controlled asthma. The studies were of good methodological quality (although it is not possible to blind people giving or receiving the intervention to which group they are in). There was no statistically significant difference in the number of asthma exacerbations and asthma severity after treatment (duration of follow-up from six months to two years). Only one study had healthcare costs as an outcome parameter, no statistical differences were found. Although not a primary outcome, quality of life is a patient-important outcome and in the three trials on 380 subjects that reported on this outcome, there was no statistically significant difference (standardised mean difference (SMD) -0.03; 95% confidence interval (CI) -0.23 to 0.17). AUTHORS' CONCLUSIONS: We found no significant difference between nurse-led care for patients with asthma compared to physician-led care for the outcomes assessed. Based on the relatively small number of studies in this review, nurse-led care may be appropriate in patients with well-controlled asthma. More studies in varied settings and among people with varying levels of asthma control are needed with data on adverse events and health-care costs.

A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four.

BACKGROUND: The recommendations for the treatment of moderate persistent asthma in the Global Initiative for Asthma (GINA) guidelines for paediatric asthma are mainly based on scientific evidence extrapolated from studies in adults or on consensus. Furthermore, clinical decision-making would benefit from formal ranking of treatments in terms of effectiveness.Our objective is to assess all randomized trial-based evidence specifically pertaining to 5-18 year olds with moderate persistent asthma. Rank the different drug treatments of GINA guideline steps 3&4 in terms of effectiveness. METHODS: Systematic review with network meta-analysis. After a comprehensive search in Central, Medline, Embase, CINAHL and the WHO search portal two reviewers selected RCTs performed in 4,129 children from 5-18 year old, with moderate persistent asthma comparing any GINA step 3&4 medication options. Further quality was assessed according the Cochrane Collaboration's tool and data-extracted included papers and built a network of the trials. Attempt at ranking treatments with formal statistical methods employing direct and indirect (e.g. through placebo) connections between all treatments. RESULTS: 8,175 references were screened; 23 randomized trials (RCT), comparing head-to-head (n=17) or against placebo (n=10), met the inclusion criteria. Except for theophylline as add-on therapy in step 4, a closed network allowed all comparisons to be made, either directly or indirectly. Huge variation in, and incomplete reporting of, outcome measurements across RCTs precluded assessment of relative efficacies. CONCLUSION: Evidence-based ranking of effectiveness of drug treatments in GINA steps 3&4 is not possible yet. Existing initiatives for harmonization of outcome measurements in asthma trials need urgent implementation.

Thyroid hormone metabolism and environmental chemical exposure.

BACKGROUND: Polychlorinated dioxins and -furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism.Influences of brominated flame retardants, PCDD/F's and dioxin like-PCBs (dl-PCB's) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3', 5,5'tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3',5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort. METHODS: Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB and PBDE levels. RESULTS: The current levels of T3 were positively correlated to BDE-99. A positive trend with FT4 and BDE-99 was also seen, while a positive correlation with T3 and dl-PCB was also seen. No correlation with TBG was seen for any of the contaminants. Neither the prenatal nor the current PCDD/F levels showed a relationship with the thyroid parameters in this relatively small group. CONCLUSION: Once again the thyroid hormone metabolism (an increase in T3) seems to have been influenced by current background levels of common environmental contaminants: dl-PCBs and BDE-99. T3 is a product of target organs and abnormalities might indicate effects on hormone transporters and could cause pathology. While the influence on T3 levels may have been compensated, because the adolescents functioned normal at the time of the study period, it is questionable if this compensation is enough for all organs depending on thyroid hormones.

[Pneumomediastinum in a child]. / Pneumomediastinum bij een kind.

BACKGROUND: Pneumomediastinum is a rare, benign condition in which air leaks through the alveolar membrane and collects in the mediastinum. Typical clinical symptoms include chest pain and dyspnoea. In the absence of underlying pathology, conservative treatment is sufficient for remission. Complications are infrequent. CASE DESCRIPTION: We present a case of a 14-year-old boy with pneumomediastinum arising during physical exercise after an earlier episode of coughing. Physical examination showed subcutaneous emphysema in the neck and praecordial systolic crepitations. A chest X-ray revealed air in the mediastinum. Conservative treatment was sufficient for full clinical and radiographic recovery. CONCLUSION: There was no underlying pathology. The diagnosis was therefore a 'spontaneous pneumomediastinum' possibly caused by a Valsalva manoeuvre after physical exercise and chronic coughing.

Monitoring pulmonary function during exercise in children with asthma.

OBJECTIVE: Exercise-induced bronchoconstriction (EIB) is defined as acute, reversible bronchoconstriction induced by physical exercise. It is widely believed that EIB occurs after exercise. However, in children with asthma the time to maximal bronchoconstriction after exercise is short, suggesting that the onset of EIB in such children occurs during exercise. AIM: In this study the authors investigate pulmonary function during exercise in cold air in children with asthma. METHODS: 33 Children with asthma with a mean age of 12.3 years and a clinical history of exercise induced symptoms, underwent a prolonged, submaximal, exercise test of 12 min duration at approximately 80% of the predicted maximum heart rate. Pulmonary function was measured before and each minute during exercise. If EIB occurred (fall in forced expiratory volume in 1 s >15% from baseline), exercise was terminated and salbutamol was administered. RESULTS: 19 Children showed EIB. In 12 of these children bronchoconstriction occurred during exercise (breakthrough EIB), while seven children showed bronchoconstriction immediately after exercise (non-breakthrough EIB). Breakthrough EIB occurred between 6 and 10 min of exercise (mean 7.75 min). CONCLUSION: In the majority of children with EIB in this study (ie, 12 out of 19), bronchoconstriction started during, and not after, a submaximal exercise test.

Constipation and colonic transit times in children with morbid obesity.

OBJECTIVES: The aim of the study was to determine the frequency of functional constipation according to the Rome III criteria in children with morbid obesity and to evaluate by measuring colonic transit times (CTTs) whether decreased colonic motility is present in these children. PATIENTS AND METHODS: Ninety-one children with morbid obesity ages 8 to 18 years, entering a prospective, randomized controlled study evaluating the effect of an outpatient versus inpatient treatment program of obesity, participated. All of the children filled out a standardized questionnaire regarding their bowel habits, and CTTs were measured using radioopaque markers. Food diaries were also recorded to evaluate their diet. RESULTS: A total of 19 children (21%) had functional constipation according to the Rome III criteria, whereas 1 child had functional nonretentive fecal incontinence. Total CTT exceeded 62 hours in only 10.5% of the children with constipation, and among them, 2 had a total CTT of >100 hours. In the nonconstipated group 8.3% had a delayed CTT. Furthermore, no difference was found between the diet of children with or without constipation, specifically not with respect to fiber and fat intake. CONCLUSIONS: Our study confirms a high frequency of functional constipation in children with obesity, using the Rome III criteria. However, abnormal colonic motility, as measured by CTT, was delayed in only a minority of patients. No relation was found between constipation in these children and fiber or fat intake.

Inhaled corticosteroids in childhood asthma: the story continues.

Inhaled corticosteroids (ICS) are the most effective anti-inflammatory drugs for the treatment of persistent asthma in children. Treatment with ICS decreases asthma mortality and morbidity, reduces symptoms, improves lung function, reduces bronchial hyperresponsiveness and reduces the number of exacerbations. The efficacy of ICS in preschool wheezing is controversial. A recent task force from the European Respiratory Society on preschool wheeze defined two different phenotypes: episodic viral wheeze, wheeze that occurs only during respiratory viral infections, and multiple-trigger wheeze, where wheeze also occurs in between viral episodes. Treatment with ICS appears to be more efficacious in the latter phenotype. Small particle ICS may offer a potential benefit in preschool children because of the favourable spray characteristics. However, the efficacy of small particle ICS in preschool children has not yet been evaluated in prospective clinical trials. The use of ICS in school children with asthma is safe with regard to systemic side effects on the hypothalamic-pituitary-adrenal axis, growth and bone metabolism, when used in low to medium doses. Although safety data in wheezing preschoolers is limited, the data are reassuring. Also for this age group, adverse events tend to be minimal when the ICS is used in appropriate doses.

Controlled trial of cycled antibiotic prophylaxis to prevent initial Pseudomonas aeruginosa infection in children with cystic fibrosis.

BACKGROUND: Initial pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) is currently treated with intensive antibiotic therapy. At this stage, inflammation and tissue injury might have already occurred. Moreover, bacterial eradication is not always achieved. Prophylactic treatment against P aeruginosa seemed to have a preventive effect in retrospective studies. A study was undertaken to establish prospectively the effect of cycled prophylactic treatment on prevention of initial P aeruginosa infection in children with CF. METHODS: This 3-year triple-blind randomised controlled trial included 65 children with CF without P aeruginosa infection. Intervention existed of 3-monthly 3-week treatments with oral ciprofloxacin and inhaled colistin or both placebo controls. The primary outcome was P aeruginosa infection. Secondary outcomes were serum anti-Pseudomonas antibodies, pulmonary function, exacerbations, chest x-ray scores, inflammation parameters, respiratory pathogens and antimicrobial resistance. RESULTS: There was no difference in acquisition of P aeruginosa infection between the control and treatment groups (annual incidence 14% vs 11%; HR 0.738, 95% CI 0.299 to 1.822). Anti-Pseudomonas antibodies emerged earlier in the control group, but this difference had disappeared after 3 years. Chronic infection was observed in 19% of controls and 12% of treated patients. Decline in pulmonary function and other clinical outcomes did not differ between the two groups. In the treatment group, significantly fewer Gram-positive bacteria and Enterobacteriaceae were observed but there were more non-P aeruginosa non-fermentative Gram-negative bacteria. Conclusions Three-monthly cycled anti-P aeruginosa prophylaxis does not reduce the risk of initial and chronic infection in P aeruginosa-negative children with CF of all ages. Shifts in bacterial colonisation demand caution. Trial Registration Number ISRCTN 11604593.

Probiotics and prebiotics in atopic dermatitis: review of the theoretical background and clinical evidence.

The prevalence of atopic dermatitis (AD) has risen over the past decades, especially in western societies. According to the revised hygiene hypothesis this increase is caused by a changed intestinal colonization pattern during infancy, which has an impact on the immune system. Manipulating the intestinal microflora with pro-, pre- or synbiotics is an innovative way to prevent or treat AD. This review provides an overview of the theoretical basis for using probiotics and prebiotics in AD and presents the current evidence from randomized controlled trials (RCTs) regarding prevention and treatment of AD and food allergy in children with pro-, pre- and synbiotics. Seven RCTs on prevention and 12 RCTs on treatment were found by searching the Pubmed, Embase and Cochrane databases. Results of these trials are conflicting. In conclusion, at this moment there is not enough evidence to support the use of pro-, pre- or synbiotics for prevention or treatment of AD in children in clinical practice.