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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 FEV 1  ≥ 13%). The severity of EIB, as measured by the maximum fall in FEV 1 , 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 FEV 1 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., (© 2017 Wiley Periodicals, Inc.)

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., (Copyright ©ERS 2015.)

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., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

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.

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.

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.

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.

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., (Copyright (c) 2009 John Wiley & Sons A/S)

Objectives: While many studies have assessed the health impacts of PCDD/Fs and PCBs on animals and humans, long-term consequences for especially adolescents, have not (yet) been well documented. This is certainly also true for the effects of PBDE exposure. As part of a longitudinal cohort study, now well into its second decade, effects of perinatal and current PCDD/F exposure, as well as current dl-PCB and PBDE exposures, on puberty, were assessed., Study Design: Prenatal, lactational and current PCDD/F, dl-PCB and PBDE concentrations were determined using GC-MS. Pubertal development and growth were assessed by means of physical examination and the Tanner scale. 33 Children (born between 1986 and 1991) consented to the current follow-up study. Outcomes were evaluated using linear regression or the non parametric Spearman's correlation coefficient., Results: A delay in initiation of breast development was found in girls (n = 18) with higher prenatal (p = 0.023) and lactational PCDD/F exposure (p = 0.048). The males revealed a negative trend with age at first ejaculation. For other endpoints on puberty and growth (pubic hair, axillary hair, genital stage, length, BMI, testicular volume, menarche) no significant relation was found with any of the measured compounds., Discussion and Conclusion: A relation between prenatal PCDD/F exposure and later initiation of breast development was seen. A Belgian study found a delay in breast development with higher current serum concentrations of dioxin-like compounds. The initiation of puberty is a complex process and it is yet not clear how dioxin-like compounds precisely affect this process prenatally. Further follow-up into adulthood is warranted, in order to detect the possibility of developing malignancies and fertility problems.

Background: The monitoring of children with asthma in primary care is based on the occurrence and frequency of asthma symptoms. We questioned whether the current approach is adequate to identify all children in whom a sufficient level of asthma control is not achieved., Aim: The aim of this study is to illustrate that in some children asthma was incorrectly considered controlled, because the children failed to report current symptoms of asthma., Patients and Methods: One hundred and nineteen children were identified with recent wheezing plus moderate or severe airway hyperresponsiveness. We analyzed whether these children reported current symptoms of asthma (as normally questioned during a routine visit)., Results: In 20 children (18%) current asthma symptoms were absent despite moderately or severe airway hyperresponsiveness and wheezing in the last year. In addition, the usage of controller medication was very poor., Conclusion: We conclude that the general practitioner has insufficient tools to adequately assess asthma control in all children. The assessment of airway hyperresponsiveness as an additional guide to manage asthma in children in general practice is recommended. In this way, better asthma control can be achieved.

Aim: The aim of the study was to assess, in a randomised, controlled design, the efficacy of different strategies to improve childhood asthma management., Method: Three interventions directed to three groups of general practitioners were compared: Group A - dissemination of a guideline; Group B - guideline dissemination plus an educational session; Group C - guideline dissemination, educational session, plus individualised treatment advice based on airway hyperresponsiveness (AHR) and symptoms. Efficacy of the three strategies was assessed by evaluating change in AHR in 362 children after one year., Results: The overall between-group effect of the severity of AHR was not significantly different (P=0.09). In Groups A and C an improvement was seen in nocturnal symptoms (P=0.02) and in Group C an improvement was seen in the prescription of inhaled corticosteroids (P=0.03)., Conclusion: In this study, the combined implementation strategy did not show a clear improvement in the management of children with asthma in general practice.

In a general practice based population 76% of 530 children inhaling asthma medication inhaled correctly. However, important differences among inhalers were found. Children with a pressurized metered-dose inhaler without a spacer device performed worst, with only 22% inhaling without essential errors. At a second evaluation of the inhaler technique, one year after the first assessment, performances with a new device were more often incorrect versus the unchanged devices (21.1% and 10.8%, respectively; p = 0.01). Providing children with a new device should be carefully controlled over time especially because these children are error prone.

The aim of this study was to investigate whether the changes that occurred in the clinical asthma score (CAS) correlated with the changes in the respiratory electromyographic (EMG) activity over the days during admission to hospital in dyspneic infants and toddlers. Sixteen infants and toddlers (9 males) were studied during admission and 7 days after discharge. The CAS was used to assess the severity of dyspnea and consists of five items: respiration rate, wheezing, retractions, observed dyspnea, and inspiration-to-expiration ratio. Each item was scaled 0, 1, or 2, with a maximum score of 10. Electrical activity from the diaphragm (di) and intercostal muscles (int) was derived from surface electrodes. The logarithm of the EMG-Activity-Ratio (log EMGAR; ratio of mean peak-to-bottom EMG activity during admission to the hospital, to that at baseline, 7 days after discharge) was used as EMG parameter. For assessing the association between the repeated observations of the CAS and the EMG measurements we used the quantity r2 obtained with analysis of covariance. On the day of admission the patients had a mean CAS of 5.9 +/- 1.2. On the day of discharge the mean CAS decreased significantly to 2.1 +/- 1.6, indicating that the CAS returned to normal values. In line with this observation, a significant decrease in the log EMGARdi and log EMGARint was observed during the stay in the hospital. Over all subjects the correlation coefficient (r) of log EMGARdi versus CAS was 0.71, log EMGARint versus CAS was 0.67, and the mean log EMGAR versus CAS was 0.75 (p < 0.01, for all values). The correlation coefficients of subjects of < or = 1 year seemed to be lower than those of subjects of > 1 year of age (p < 0.01) and female subjects showed higher correlation coefficients than males. This study showed a moderate, but significant, relationship between the changes that occurred in the CAS and the changes in respiratory EMG activity during admission to hospital in dyspneic infants and toddlers. Moreover, the correlation coefficients of the combined leads of the intercostals and diaphragm (mean log EMGAR) were higher than those of the separate leads. The EMG measurements would extend diagnostic possibilities and would provide an objective measure to evaluate the clinical course of the disease and the efficacy of therapy in infants and toddlers with recurrent wheezing disorders.

The Asthma Insight and Reality in Europe (AIRE) study showed that the current management and treatment of asthma in Europe falls short of the goals set in the GINA guidelines. Patient care may be negatively influenced by the physicians' underestimation of their patients' disease state, and overestimation of their patients' knowledge of asthma management. We interviewed 118 paediatricians and 152 general practitioners (response rate 70 and 86%, respectively) in order to get an insight into the physicians view on his patients' asthma management. A questionnaire containing similar items to those used in the AIRE study was used. Dutch physicians believe that the asthma of the majority of their patients is well controlled and underestimate the prevalence of daytime symptoms. They believe that their patients are aware of the differences between reliever medication and maintenance medication and overestimate the number of patients in possession of a written action plan. Dutch paediatricians and general practitioners underestimate the severity of their patients' disease state and overestimate their patients' knowledge of disease management.

Background: For the diagnosis of asthma in young children, GPs have to rely on history taking and physical examination, as spirometry is not possible. The additional diagnostic value of specific immunoglobulin E (IgE) to inhalent allergens remains unclear., Aim: To assess the predictive accuracy of specific IgE to cat, dog, and/or house dust mites in young children for the subsequent development of asthma at the age of 6 years., Design of Study: Prospective follow-up study., Setting: Seventy-two general practices., Method: A total of 654 children, aged 1-4 years, visiting their GPs for persistent coughing (>/= 5 days), were tested for IgE antibodies by radio allergosorbent testing (RAST). Parents completed a questionnaire on potential risk indicators. Those children who showed an IgE-positive status (12.7%) and a random sample of those with an IgE-negative status (<0.5 U/ml) were followed up to the age of 6 years when the asthma status was established. The main outcome measure was asthma at the age of 6 years (combination of both symptoms and/or use of asthma medication, and impaired lung function)., Results: Addition of RAST results to a prediction model based on age, wheeze, and family history of pollen allergy increased the area under the receiver operating characteristic (ROC) curve from 0.76 to 0.87. Furthermore, RAST improved patient differentiation as indicated by a change in the range of asthma probabilities from 6-75% before the IgE test, to 1-95% after the IgE-test., Conclusion: Sensitisation to inhalant allergens in 1-4-year-olds, as shown by RAST, is a useful diagnostic indicator for the presence of asthma at the age of 6 years, even after a clinical history has been obtained. This model should preferably be validated in a new population before it can be applied in practice.

Background: Perinatal risk factors are associated with lung function and respiratory symptoms in adult life. Whether the same holds for distinctive asthma features, such as bronchial hyperresponsiveness (BHR) and atopy, has scarcely been studied., Objective: We sought to identify the perinatal risk factors for the development of BHR and atopy., Methods: BHR and atopy were measured after 20 years' follow-up in 597 of 3162 babies born from 1975 through 1978. Factors directly related to delivery of these children were studied in association with the presence of BHR and atopy., Results: Twenty-five percent had BHR, and 47% had atopy. Delivery duration of longer than 12 hours was associated with the development of atopy (odds ratio [OR], 2.24; 95% CI, 1.30-3.86), and severe respiratory infection in the first year of life was associated with the development of BHR (OR, 2.69; 95% CI, 1.41-5.16). Nonatopic subjects born after induced labor and current smokers were more likely to have BHR (ORs of 2.41 [95% CI, 1.07-5.41] and 2.50 [95% CI, 1.12-5.59], respectively). Prenatal smoke exposure and childhood pet keeping decreased the risk for atopy, especially in BHR-positive subjects (ORs of 0.51 [95% CI, 0.27-0.99] and 0.46 [95% CI, 0.24-0.88], respectively)., Conclusions: It has been shown that events before or during birth still have an effect on respiratory health 20 years later. We put forward that an extreme hormonal status during delivery primes the fetal immune system toward atopy development. Furthermore, a severe respiratory infection in the first year of life appears associated with BHR development, and prenatal smoke exposure might be protective for the development of atopy, yet explanatory mechanisms are lacking thus far.

The aim of the study was to investigate the association between surface electromyographic (EMG) activity of the diaphragm and intercostal muscles, and clinical symptoms (wheeze, cough, increased respiratory rate and prolonged expiration) during bronchial challenge testing and after administration of salbutamol in asthmatic pre-school children. A histamine challenge test was performed in 20 asthmatic pre-school children. The histamine dose at the appearance of 1 or more clinical symptoms was defined as the maximum histamine provocation dose (PDcs). The clinical symptoms were recorded with a microphone over the trachea. The logarithm of the EMG-Activity-Ratio (log EMGAR; mean peak activity ratio to baseline of respiratory muscles during tidal breathing) was used as EMG parameter. In both the diaphragmatic and the intercostal log EMGAR values a linear increase was observed in the four histamine dose-steps prior to PDcs. At PDcs the mean log EMGAR of the diaphragm (di) and intercostal muscles (int) was significantly increased as compared to the baseline values. After administration of salbutamol the log EMGARdi and log EMGARint returned to baseline values and the clinical symptoms normalized in all children. At PDcs, no significant differences in the log EMGAR values could be detected at the appearance of the distinctive clinical symptoms, which suggests that wheezing is not the only indicator for the detection of airway responsiveness in young children. We found a linear association between histamine dose and the increase in surface diaphragmatic and intercostal respiratory EMG activity during a bronchial challenge test in pre-school asthmatic children, which returned to baseline values after inhalation of salbutamol. These findings support the idea that EMG measurements of the diaphragm and intercostal muscles may offer an opportunity to estimate airway response in young children in an alternative way.

The aim of the study was to investigate the association between electromyography (EMG) of the diaphragm and intercostal muscles and the forced expiratory volume in 1 s (FEV(1)) at different levels of histamine-induced airflow limitation, and the response to salbutamol. Moreover, we assessed the reproducibility of the EMG measurements on 2 different occasions during different levels of airflow limitation in asthmatic school children. Fourteen children with asthma performed 2 histamine challenges with a 24-h time interval and 1 child performed 1 histamine challenge. The EMG signals were derived from surface electrodes. The logarithm of the EMG-activity-ratio (log EMGAR; mean peak-bottom ratio of respiratory muscle activity) was used as EMG parameter. The log EMGAR of the diaphragm (di) and the log EMGAR of the intercostal muscles (int) associated well with the histamine-induced fall in FEV(1) at 5% steps from the baseline value. After administration of salbutamol log EMGARdi and log EMGARint returned to baseline mean peak-bottom values (for all leads P<0.001). The EMGARdi and EMGARint values were reproducible at different levels of airflow limitation. This study showed that EMGARdi and EMGARint as a parameter for a change in electrical activity of the diaphragm and intercostal muscles associated well with FEV(1), was reversible after salbutamol and was reproducible at different levels of histamine-induced airflow limitation in asthmatic school children.