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Objective: To evaluate longitudinal associations between recreational screen time and sleep in early childhood, and attention-deficit/hyperactivity disorder (ADHD) at age 8 to 10 years. Method: Questionnaires from 2,768 mother-child pairs from the Dutch KOALA Birth Cohort Study were used. General estimating equation logistic regression analyses examined associations between screen time and sleep at age 2, 4, and 6, and ADHD at age 8 to 10. Linear regression analysis examined associations between television time, sleep and CBCL/2-3 scores at age 2. Results: Longitudinally, neither screen time nor sleep were associated with ADHD. Cross-sectionally, CBCL/2-3 externalizing symptom scores increased by 0.03 with every hour television time (95% CI 0.002–0.05) and increased by 0.02 per hour of less sleep (95% CI −0.03–−0.01). Conclusion: Despite an association with externalizing symptoms at age 2, screen time and sleep in early childhood were not associated with ADHD. Carefulness is warranted when extrapolating cross-sectional associations at early age to an ADHD diagnosis.

Exhaled breath analysis has great potential in diagnosing various respiratory and non-respiratory diseases. In this study, we investigated the influence of inhaled corticosteroids (ICS) on exhaled volatile organic compounds (VOCs) of wheezing preschool children. Furthermore, we assessed whether exhaled VOCs could predict a clinical steroid response in wheezing preschool children. We performed a crossover 8-week ICS trial, in which 147 children were included. Complete data were available for 89 children, of which 46 children were defined as steroid-responsive. Exhaled VOCs were measured by GC-tof-MS. Statistical analysis by means of Random Forest was used to investigate the effect of ICS on exhaled VOCs. A set of 20 VOCs could best discriminate between measurements before and after ICS treatment, with a sensitivity of 73% and specificity of 67% (area under ROC curve = 0.72). Most discriminative VOCs were branched C11H24, butanal, octanal, acetic acid and methylated pentane. Other VOCs predominantly included alkanes. Regularised multivariate analysis of variance (rMANOVA) was used to determine treatment response, which showed a significant effect between responders and non-responders (p < 0.01). These results show that ICS significantly altered the exhaled breath profiles of wheezing preschool children, irrespective of clinical treatment response. Furthermore, exhaled VOCs were capable of determining corticosteroid responsiveness in wheezing preschool children.

Selected-Ion Flow-Tube Mass Spectrometry (SIFT-MS) has been applied in a clinical context as diagnostic tool for breath samples using target biomarkers. Exhaled breath sampling is non-invasive and therefore much more patient friendly compared to bronchoscopy, which is the golden standard for evaluating airway inflammation. In the actual pilot study, 55 exhaled breath samples of children with asthma, cystic-fibrosis and healthy individuals were included. Rather than focusing on the analysis of target biomarkers or on the identification of biomarkers, different data analysis strategies, including a variety of pretreatment, classification and discrimination techniques, are evaluated regarding their capacity to distinguish the three classes based on subtle differences in their full scan SIFT-MS spectra. Proper data-analysis strategies are required because these full scan spectra contain much external, i.e. unwanted, variation. Each SIFT-MS analysis generates three spectra resulting from ionmolecule reactions of analyte molecules with H3O+, NO+ and O-2(+). Models were built with Linear Discriminant Analysis, Quadratic Discriminant Analysis, Soft Independent Modelling by Class Analogy, Partial Least Squares - Discriminant Analysis, K-Nearest Neighbours, and Classification and Regression Trees. Perfect models, concerning overall sensitivity and specificity (100% for both) were found using Direct Orthogonal Signal Correction (DOSC) pretreatment. Given the uncertainty related to the classification models associated with DOSC pretreatments (i.e. good classification found also for random classes), other models are built applying other preprocessing approaches. A Partial Least Squares - Discriminant Analysis model with a combined pre-processing method considering single value imputation results in 100% sensitivity and specificity for calibration, but was less good predictive. Pareto scaling prior to Quadratic Discriminant Analysis resulted in 41/55 correctly classified samples for calibration and 34/55 for cross-validation. In future, the uncertainty with DOSC and the applicability of the promising preprocessing methods and models must be further studied applying a larger representative data set with a more extensive number of samples for each class. Nevertheless, this pilot study showed already some potential for the untargeted SIFT-MS application as a rapid pattern-recognition technique, useful in the diagnosis of clinical breath samples.

The Coronavirus pandemic stresses the importance of eHealth techniques to monitor patients at home. Home monitoring of lung function in asthma and cystic fibrosis (CF) may help to detect deterioration of lung function at an early stage, but the reliability is unclear. We investigated whether lung function measurements at home were comparable to measurements during clinical visits. We analysed prospectively collected data of two one-year observational cohort studies in 117 children (36 with CF and 81 with asthma). All patients performed forced expiratory volume in one second (FEV1) measurements with a monitor at home. Paired FEV1 measurements were included if the measurement on the home monitor was performed on the same day as the FEV1 measurement on the pneumotachometer during a two monthly clinical visit. Bland-Altman plots and linear mixed model analysis were used. The mean difference (home measurement was subtracted from clinical measurement) in FEV1 was 0.18 L in CF (95% confidence interval (CI) 0.08&ndash, 0.27 L, p &lt, 0.001) and 0.12 L in asthma (95%CI 0.05&ndash, 0.19 L, 0.001). FEV1 measurements at home were significantly lower than clinically obtained FEV1 measurements, which has implications for the application of this technique in the daily clinical situation.

Background Maternal overweight and obesity are related to several health risks in the periods before, during and after pregnancy including a higher risk of gestational diabetes mellitus, preeclampsia and preterm birth. At the same time, women’s daily life quickly changes in these periods. Therefore, we hypothesize that the value of determinants of lifestyle behavior within different levels of the socio-ecological model differ accordingly and influence lifestyle behavior. These dynamics of determinants of lifestyle behavior in the periods before, during and after pregnancy are unexplored and therefore evaluated in this study. These insights are needed to offer appropriate guidance to improve lifestyle in women of childbearing age. Methods Individual semi-structured interviews were conducted before, during or after pregnancy in 26 women with overweight or obesity living in the Netherlands. Questions covered all levels of the socio-ecological model, i.e. intrapersonal, interpersonal, institutional and environmental/societal. All interviews were transcribed and coded. Results Determinants at all levels of the socio-ecological model were perceived as relevant by women of childbearing age. Various determinants were mentioned including knowledge of a healthy lifestyle, social support, access to customized lifestyle guidance, and distance to healthy lifestyle supporting activities. The importance women attributed to determinants differed between the periods before, during and after pregnancy. Before pregnancy, child’s wellbeing as motivator for adopting a healthy lifestyle was mentioned less frequently than during and after pregnancy. Women described that the interplay and balance between determinants varied on a daily basis, and not merely per period. This was often expressed as fluctuation in energy level per day which influences their willingness to put effort in making healthy choices. Conclusions Findings of this study confirm the importance of determinants at multiple socio-ecological levels for shaping lifestyle behavior in women of childbearing age. The findings add to current insights that the perceived importance of determinants and their interplay differ before, during and after pregnancy. They influence lifestyle behavior decisions, not only per period but even on a daily basis, in particular in this phase of life. This perspective can be helpful in optimizing lifestyle guidance for women of childbearing age in order to prevent perinatal complications.

Managing pediatric asthma includes optimizing both asthma control and asthma-specific quality of life (QoL). However, it is unclear to what extent asthma-specific QoL is related to asthma control or other clinical characteristics over time. The aims of this study were to assess in children longitudinally: (1) the association between asthma control and asthma-specific QoL and (2) the relationship between clinical characteristics and asthma-specific QoL. In a 12-month prospective study, asthma-specific QoL, asthma control, dynamic lung function indices, fractional exhaled nitric oxide, the occurrence of exacerbations, and the use of rescue medication were assessed every 2 months. Associations between the clinical characteristics and asthma-specific QoL were analyzed using linear mixed models. At baseline, the QoL symptom score was worse in children with asthma and concomitant chronic rhinitis compared to asthmatic children without chronic rhinitis. An improvement of asthma control was longitudinally associated with an increase in asthma-specific QoL (p-value < 0.01). An increased use of β2-agonists, the occurrence of wheezing episodes in the year before the study, the occurrence of an asthma exacerbation in the 2 months prior to a clinical visit, and a deterioration of lung function correlated significantly with a decrease in the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) total score (p-values ≤ 0.01). Chronic rhinitis did not correlate with changes in the PAQLQ score over 1 year. The conclusion was that asthma control and asthma-specific QoL were longitudinally associated, but were not mutually interchangeable. The presence of chronic rhinitis at baseline did influence QoL symptom scores. β2-agonist use and exacerbations before and during the study were inversely related to the asthma-specific QoL over time.

Background We evaluated the effectiveness of different recruitment strategies used in a study aimed at eliminating/reducing second-hand smoke (SHS) exposure in Dutch children 0–13 years of age with a high risk of asthma. Methods The different strategies include: 1) questionnaires distributed via home addresses, physicians or schools of the children; 2) cohorts from other paediatric studies; 3) physicians working in the paediatric field (family physicians, paediatricians and Youth Health Care (YHC) physicians); and 4) advertisements in a local newsletter, at child-care facilities, and day-care centres. Results More than 42,782 families were approached to take part in the screening of which 3663 could be assessed for eligibility. Of these responders, 196 families met the inclusion criteria for the study. However, only 58 (one third) could be randomised in the trial, mainly because of no interest or time of the parents. The results showed that recruiting families who expose their children to SHS exposure is very challenging, which may be explained by lack of ‘recognition’ or awareness that SHS occurs in homes. The presence of asthma in the family, respiratory symptoms in the children, and even incentives did not increase parental motivation for participation in the study. Conclusions The recruitment process for an intervention program addressing SHS exposure in children was considerably more challenging and time consuming than anticipated. Barriers at both a parents level and a doctor’s level can be discriminated. Electronic supplementary material The online version of this article (10.1186/s12887-018-0983-4) contains supplementary material, which is available to authorized users.

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1 (IL1RL1 or ST2) is a well-replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3 years-old wheezers do not predict doctors' diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95% CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95% CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age.

OBJECTIVE: Current data about Attention Deficit Hyperactivity Deficiency (ADHD) guideline use in the Netherlands are absent. This study analysed ADHD guideline use among different healthcare workers, and the use of key elements from these guidelines to diagnose ADHD.METHOD: A survey assessing ADHD guideline use was distributed throughout the Netherlands to various health care professionals. Only professionals involved during the diagnostic process were included.RESULTS: Response rate among GPs was low (111/1450), but high among other health care professionals (251/287). A total of 362 surveys were analysed, 186 responders (51%) were involved during the diagnostic process. Overall guideline use was 64.5%; the national multidisciplinary guideline or a guideline made by a professional's own institution were most used. Psychiatrists, psychologists and paediatricians reported compliance with key elements of the guidelines such as gathering information from a third party (> 90%) and carrying out a developmental history (> 88%). Use of a standardized interview (CONCLUSION: Despite low general use of guidelines, psychiatrists, psychologists and paediatricians use similar key elements of ADHD guidelines. This study provides opportunities to improve care through increasing familiarity with ADHD guidelines and the use of standardized interviews.

To identify potential risk factors for lung disease progression in children with cystic fibrosis (CF), we studied the longitudinal data of all children with CF (aged ≥5 years) registered in the Dutch CF Registry (2009–2014).Lung disease progression was expressed as a decline in lung function (forced expiratory volume in 1 s (FEV1) % pred) and pulmonary exacerbation rate. Potential risk factors at baseline included sex, age, best FEV1 % pred, best forced vital capacity % pred, genotype, body mass index z-score, pancreatic insufficiency, medication use (proton pump inhibitors (PPIs), prophylactic antibiotics and inhaled corticosteroids), CF-related diabetes, allergic bronchopulmonary aspergillosis and colonisation with Pseudomonas aeruginosa.The data of 545 children were analysed. PPI use was associated with both annual decline of FEV1 % pred (p=0.017) and future pulmonary exacerbation rate (p=0.006). Moreover, lower FEV1 % pred at baseline (p=0.007), prophylactic inhaled antibiotic use (p=0.006) and pulmonary exacerbations in the baseline year (p=0.002) were related to pulmonary exacerbations in subsequent years.In a cohort of Dutch children with CF followed for 5 years, we were able to identify several risk factors for future exacerbations. In particular, the association between PPI use and lung disease progression definitely requires further investigation.

After a positive newborn screening test for cystic fibrosis (CF), a sweat test is performed to confirm the diagnosis. The success rate of the generally acknowledged methods (Macroduct/Gibson and Cooke) in newborns varies between 73 and 99 %. The Nanoduct sweat test system is easier to perform and less sweat is needed. The main aim of this study was to measure the success rate of the Nanoduct compared to current approved sweat test methods in a newborn population. After informed consent of the parents, newborns with a positive screening test for CF were included. The Macroduct or Gibson and Cooke and Nanoduct were performed in all infants, during the same appointment. The chloride concentration was determined by standard coulorimetry; conductivity was measured directly and converted to a NaCl molarity. One hundred eight newborns were included: 17 with CF, 7 with cystic fibrosis transmembrane regulator (CFTR)-related metabolic syndrome (CRMS), and 84 healthy children. The success rate of the Nanoduct was 93 % and for the Macroduct/Gibson and Cooke 79 % (McNemar, p = 0.002). The Nanoduct detected the same CF patients as the Macroduct/Gibson and Cooke; one CF patient had an equivocal result for both tests, and no patients were missed. The area under the receiver operating characteristic curve for detection of CF with the Nanoduct was 0.999, with ideal cutoff levels of 91 and 66 mmol/l, comparable to former studies.Conclusion: The success rate of the Nanoduct to collect sufficient sweat in infants was higher compared to the Macroduct and Gibson and Cooke.

We tested the effectiveness of a program consisting of motivational interviewing (MI) and feedback of urine cotinine to stop passive smoking (PS) in children at risk for asthma. Fifty-eight families with children 0–13 years with a high risk of asthma and PS exposure were randomised in a one-year follow-up study. The intervention group received the intervention program during 6 sessions (1/month) and the control group received measurements (questionnaires, urine cotinine, and lung function) only. The primary outcome measure was the percentage of families stopping PS (parental report verified and unverified with the child’s urine cotinine concentration

Pulmonary exacerbations (PEx) in Cystic Fibrosis (CF) are associated with an increased morbidity and even mortality. We investigated whether early detection of PEx in children with CF is possible by electronic home monitoring of symptoms and lung function. During this one-year prospective multi-centre study, 49 children with CF were asked to use a home monitor three times a week. Measurements consisted of a respiratory symptom questionnaire and assessment of Forced Expiratory Volume in one second (FEV1). Linear mixed-effects and multiple logistic regression analyses were used. In the 2 weeks before a PEx, the Respiratory Symptom Score (RSS) of the home monitor increased (p = 0.051). The FEV1 as percentage of predicted (FEV1%pred) did not deteriorate in the 4 weeks before a PEx. Nevertheless, the FEV1%pred at the start of exacerbation was significantly lower than the FEV1%pred in the non-exacerbation group (mean difference 16.3%, p = 0.012). The combination of FEV1%pred and RSS had a sensitivity to predict an exacerbation of 92.9% (CI 75.0–98.8%) and a specificity of 88.9% (CI 50.7–99.4%). The combination of home monitor FEV1%pred and RSS can be helpful to predict a PEx in children with CF at an early stage.

Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

There is increasing evidence that obesity is related to asthma development and severity. However, it is largely unknown whether weight reduction can influence asthma management, especially in children.To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with (a high risk of developing) asthma.An 18-month weight-reduction randomized controlled trial was conducted in 87 children with overweight/obesity and asthma. Every six months, measurements of anthropometry, lung function, lifestyle parameters and inflammatory markers were assessed. Analyses were performed with linear mixed models for longitudinal analyses.After 18 months, the body mass index-standard deviation score decreased by -0.14±0.29 points (p0.01) in the intervention group and -0.12±0.34 points (p0.01) in the control group. This change over time did not differ between groups (p0.05). Asthma features (including asthma control and asthma-related quality of life) and lung function indices (static and dynamic) improved significantly over time in both groups. The FVC% predicted improved over time by 10.1 ± 8.7% in the intervention group (p0.001), which was significantly greater than the 6.1 ± 8.4% in the control group (p0.05).Clinically relevant improvements in body weight, lung function and asthma features were found in both the intervention and control group, although some effects were more pronounced in the intervention group (FVC, asthma control, and quality of life). This implies that a weight reduction intervention could be clinically beneficial for children with asthma.ClinicalTrials.gov NCT00998413.

Background Many children stand to benefit from being asthma-free for life with primary (i.e., prenatally started) prevention addressing one environmental exposure in a unifaceted (UF) approach or at least two in a multifaceted (MF) approach. We assessed the cost-effectiveness of primary prevention programmes for Dutch children in a decision-analytic framework. Methods A decision-analytic tree model analysing healthcare costs and asthma cases prevented was developed to compare usual care (UC) with two UF and three MF programmes on the primary prevention of asthma amongst children. Programmes were evaluated through incremental cost-effectiveness ratios and net monetary benefits. Decision and parameter uncertainty were subjected to value-of-information analyses. Results The current UC and one of three MF programmes dominated the other alternatives. The MF programme was more costly but also more effective than UC at an incremental cost-effectiveness ratio of (sic)8,209.20/additional asthma case prevented. The value of perfect information to reduce uncertainty was (sic)291.6M at its lowest. Most of the uncertainty in the cost-effectiveness threshold was attributable to the probability and cost estimates for low-risk children. Conclusion This study supports the feasibility of a structured programme that simultaneously addresses exposure to house dust mites, pet dander, environmental tobacco, and breast-feeding as a cost-effective alternative to UC in the primary prevention of asthma amongst children.

Exercise can provoke asthma symptoms, such as dyspnoea, in children with asthma. Exercise-induced bronchoconstriction (EIB) is prevalent in 40-90% of children with asthma. Conversely, exercise can improve physical fitness. The purpose of this paper is to provide a systematic review of the literature regarding the effects of exercise training in children with asthma, particularly in relation to: EIB, asthma control, pulmonary function, cardiorespiratory parameters and parameters of underlying pathophysiology. A systematic search in several databases was performed. Controlled trials that undertook a physical training programme in children with asthma (aged 6-18 years) were selected. Twenty-nine studies were included. Training had positive effects on several cardiorespiratory fitness parameters. A few studies demonstrated that training could improve EIB, especially in cases where there was sufficient room for improvement. Peak expiratory flow was the only lung function parameter that could be improved substantially by training. The effects of training on asthma control, airway inflammation and bronchial hyper-responsiveness were barely studied. Owing to the overall beneficial effects of training and the lack of negative effects, it can be concluded that physical exercise is safe and can be recommended in children with asthma. A training programme should have a minimum duration of 3 months, with at least two 60 min training sessions per week, and a training intensity set at the (personalised) ventilatory threshold. Further research is recommended regarding the effects of exercise on underlying pathophysiological mechanisms and asthma control in children with asthma.

Background: Early diagnosis through newborn screening (NBS) and early treatment of cystic fibrosis (CF) do lead to better prognosis. In the Netherlands, the median age for a clinical diagnosis is six months, and after newborn screening this is 30 days. It is unknown if being diagnosed at the age of six months or before two months leads to a clinically relevant difference of the clinical condition at the time of diagnosis.Aim: The aim of this study is to assess the differences in clinical parameters at diagnosis between children with CF identified by newborn screening (NBS) or by clinical diagnosis (CD) in the Netherlands.Methods: From July 1st, 2007 to January 1st, 2012 all newly diagnosed CF patients were reported to the Dutch Paediatric Surveillance Unit (DPSU). All paediatricians received a questionnaire to collect data on mutations and clinical condition at diagnosis. Non-classical CF was excluded from the analysis on clinical condition.Results: 204 new CF diagnoses were reported to the DPSU, 33 were reported twice and three had no CF after further testing. 127 questionnaires were returned (76%); 85 children were diagnosed because of clinical symptoms, 40 after NBS and two because of a positive family history. The median age at diagnosis was 34 weeks for a clinical diagnosis and 3 weeks after NBS. Non-classical CF was more prevalent in the NBS group (6 clinical, 14 NBS), mostly F508de1/R117H7T (12). Compared to the NBS group, significantly more patients in the CD group showed failure to thrive, respiratory symptoms, and hospitalizations. 62% of the CD group showed abnormal signs at physical examination compared to 4% of the NBS group.Conclusion: At the time of diagnosis infants detected after NBS are in a significantly better condition than after a clinical diagnosis. Growth retardation is already seen when after NBS the diagnosis is confirmed, but NBS leads to a diagnosis before respiratory symptoms have developed. (C) 2014 Elsevier Inc. All rights reserved.

Childhood asthma is characterized by chronic airway inflammation. Integrative genomic analysis of airway inflammation on genetic and protein level may help to unravel mechanisms of childhood asthma. We aimed to employ an integrative genomic approach investigating inflammation markers on DNA, mRNA, and protein level at preschool age in relationship to asthma development.In a prospective study, 252 preschool children (202 recurrent wheezers, 50 controls) from the Asthma DEtection and Monitoring (ADEM) study were followed until the age of six. Genetic variants, mRNA expression in peripheral blood mononuclear cells, and protein levels in exhaled breath condensate for intercellular adhesion molecule 1 (ICAM1), interleukin (IL)4, IL8, IL10, IL13, and tumor necrosis factor α were analyzed at preschool age. At six years of age, a classification (healthy, transient wheeze, or asthma) was based on symptoms, lung function, and medication use.The ICAM1 rs5498 A allele was positively associated with asthma development (p = 0.02) and ICAM1 gene expression (p = 0.01). ICAM1 gene expression was positively associated with exhaled levels of soluble ICAM1 (p = 0.04) which in turn was positively associated with asthma development (p = 0.01). Furthermore, rs1800872 and rs1800896 in IL10 were associated with altered IL10 mRNA expression (p0.01). Exhaled levels of IL4, IL10, and IL13 were positively associated with asthma development (p0.01).In this unique prospective study, we demonstrated that ICAM1 is associated with asthma development on DNA, mRNA, and protein level. Thus, ICAM1 is likely to be involved in the development of childhood asthma.

The hypothesis was that prediction of asthma exacerbations in children is possible by profiles of exhaled volatile organic compounds (VOCs), a noninvasive measure of airway inflammation. The aims of the present study were to determine: 1) whether VOCs in exhaled breath are able to predict asthma exacerbations; and 2) the time course and chemical background of the most predictive VOCs. A prospective study was performed in 40 children with asthma over 1 year. At standard 2-month intervals, exhaled nitric oxide fraction (FeNO), VOC profiles in exhaled breath samples, lung function and symptoms were determined in a standardised way. VOC profiles were analysed by gas chromatography-time-of-flight mass spectrometry. 16 out of 40 children experienced an exacerbation. With support vector machine analysis, the most optimal model of baseline measurements versus exacerbation within patients was based on six VOCs (correct classification 96%, sensitivity 100% and specificity 93%). The model of baseline values of patients with compared to those without an exacerbation consisted of seven VOCs (correct classification 91%, sensitivity 79% and specificity 100%). FeNO and lung function were not predictive for exacerbations. This study indicates that a combination of different exhaled VOCs is able to predict exacerbations of childhood asthma.

Background Asthma and obesity are highly prevalent in children, and are interrelated resulting in a difficult-to-treat asthma-obesity phenotype. The exact underlying mechanisms of this phenotype remain unclear, but decreased physical activity (PA) could be an important lifestyle factor. We hypothesize that both asthma and overweight/obesity decrease PA levels and interact on PA levels in asthmatic children with overweight/obesity. Methods School-aged children (n = 122) were divided in 4 groups (healthy control, asthma, overweight/obesity and asthma, and overweight/obesity). Children were asked to perform lung function tests and wear an activity monitor for 7 days. PA was determined by: step count, active time, screen time, time spent in organized sports and active transport forms. We used multiple linear regression techniques to investigate whether asthma, body mass index-standard deviation score (BMI-SDS), or the interaction term asthma x BMI-SDS were associated with PA. Additionally, we tested if asthma features (including lung function and medication) were related to PA levels in asthmatic children. Results Asthma, BMI-SDS and the interaction between asthma x BMI-SDS were not related to any of the PA variables (p ≥ 0.05). None of the asthma features could predict PA levels (p ≥ 0.05). Less than 1 in 5 children reached the recommended daily step count guidelines of 12,000 steps/day. Conclusion We found no significant associations between asthma, overweight and PA levels in school-aged children in this study. However, as PA levels were worryingly low, effective PA promotion in school-aged children is necessary. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-3600-1) contains supplementary material, which is available to authorized users.

BACKGROUND: There is increasing evidence that obesity is related to asthma development and severity. However, it is largely unknown whether weight reduction can influence asthma management, especially in children.OBJECTIVE: To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with (a high risk of developing) asthma.METHODS: An 18-month weight-reduction randomized controlled trial was conducted in 87 children with overweight/obesity and asthma. Every six months, measurements of anthropometry, lung function, lifestyle parameters and inflammatory markers were assessed. Analyses were performed with linear mixed models for longitudinal analyses.RESULTS: After 18 months, the body mass index-standard deviation score decreased by -0.14±0.29 points (p0.05). Asthma features (including asthma control and asthma-related quality of life) and lung function indices (static and dynamic) improved significantly over time in both groups. The FVC% predicted improved over time by 10.1 ± 8.7% in the intervention group (pCONCLUSIONS & CLINICAL RELEVANCE: Clinically relevant improvements in body weight, lung function and asthma features were found in both the intervention and control group, although some effects were more pronounced in the intervention group (FVC, asthma control, and quality of life). This implies that a weight reduction intervention could be clinically beneficial for children with asthma.TRIAL REGISTRATION: ClinicalTrials.gov NCT00998413.

Item does not contain fulltext The relationship between exhaled inflammatory markers and asthma control in children is unclear. To explore the association between inflammatory markers in exhaled breath (fractional nitric oxide (FeNO), volatile organic compounds (VOCs), cytokines/chemokines) and asthma control. To assess whether exhaled inflammatory markers are able to discriminate between children with persistently controlled/uncontrolled asthma. 96 asthmatic children were followed-up in a one-year observational study. Every 2 months, the following parameters were assessed: asthma control, FeNO, lung function (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), exhaled VOCs, and cytokines/chemokines in exhaled breath condensate (EBC). Random Forest was used to analyse the relationship between exhaled inflammatory markers and asthma control. For each model, patients were randomly selected for a training set and validation set. To assess the accuracy of the classification models, receiver operating characteristic-curves (ROC-curves) were generated. No significant association was found between the exhaled inflammatory markers (FeNO, markers in EBC, VOCs) and asthma control (area under the ROC-curve 49%). However, 15 exhaled VOCs could discriminate between subgroups of children with persistently controlled and uncontrolled asthma during all clinical visits (area under the ROC-curve 86%). Adding FeNO and markers in EBC to this model, did not lead to a more accurate classification (area under the ROC-curve 87%). There was no association between exhaled inflammatory markers and asthma control in children. However, children with persistently controlled or uncontrolled asthma during the 12 month study period could be discriminated by a set of VOCs.

Measurement of bronchial and alveolar exhaled nitric oxide (NO) levels could be of clinical importance for the treatment of asthma. To discriminate between alveolar and bronchial NO, measurements need to be assessed at various flow rates. To study the feasibility, linearity, and long-term repeatability of NO measurements at four different exhalation flow rates in children with asthma. Twenty-one children with moderate persistent asthma, aged 6-12 yrs, were included in the study. NO was measured according to the ATS/ERS guidelines, using the NIOX analyzer with flow restrictors of 30, 50, 100, and 200 ml/s. Duration of the measurements ranged from 6-10 s, depending on the flow rate. The tests were repeated 3 and 6 months after the first NO measurement. Feasibility of NO measurements at these four flow rates increased from 67% to 91% and 95% at the first, second and third visit, respectively. A significant learning effect was present. Age and lung function indices did not influence success or failure of the tests. At the first measurements occasions, no problems occurred during the NO analysis at a 100 ml/s flow rate. There was a 75-90% success rate when performing the test using flow rates of 30, 50, and 200 ml/s. However, repeating the tests resulted in a 100% success rate. Measurements were not successful if: (i) children ran out of air; (ii) NO concentration exceeded 200 ppb; (iii) the measured NO flow was unstable; and (iv) the NO plateau was not formed. This study showed good feasibility and linearity of NO measurements in asthmatic children of 6 yrs and over at flow rates between 50-200 ml/s. A significant learning effect was present. The long-term reproducibility of alveolar and bronchial NO values during 6 months was moderate.

Summary Background The correct diagnosis of asthma in young children is often hard to achieve, resulting in undertreatment of asthmatic children and overtreatment in transient wheezers. Objectives To develop a new diagnostic tool that better discriminates between asthma and transient wheezing and that leads to a more accurate diagnosis and hence less undertreatment and overtreatment. A first stage in the development of such a tool is the ability to discriminate between asthmatic children and healthy controls. The integrative analysis of large numbers of volatile organic compounds (VOC) in exhaled breath has the potential to discriminate between various inflammatory conditions of the respiratory tract. Methods Breath samples were obtained and analysed for VOC by gas chromatography–mass spectrometry from asthmatic children (n=63) and healthy controls (n=57). A total of 945 determined compounds were subjected to discriminant analysis to find those that could discriminate diseased from healthy children. A set of samples from both asthmatic and healthy children was selected to construct a model that was subsequently used to predict the asthma or the healthy status of a test group. In this way, the predictive value of the model could be tested. Measurements and main results The discriminant analyses demonstrated that asthma and healthy groups are distinct from one another. A total of eight components discriminated between asthmatic and healthy children with a 92% correct classification, achieving a sensitivity of 89% and a specificity of 95%. Conclusion The results show that a limited number of VOC in exhaled air can well be used to distinguish children with asthma from healthy children. Cite this as: J. W. Dallinga, C. M. H. H. T. Robroeks, J. J. B. N. van Berkel, E. J. C. Moonen, R. W. L. Godschalk, Q. Jobsis, E. Dompeling, E. F. M. Wouters and F. J. van Schooten, Clinical & Experimental Allergy, 2010 (40) 68–76.

BACKGROUND: Previous studies have suggested the existence of enteropathy in cystic fibrosis (CF), which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use. METHODS: Sixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP), a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1), exocrine pancreatic insufficiency (EPI), CF-related diabetes (CFRD) and use of proton pump inhibitors (PPI) were obtained from the medical charts. RESULTS: Serum I-FABP levels were elevated in CF patients as compared with controls (p

BACKGROUND: The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. OBJECTIVE: To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. MATERIALS AND METHODS: In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p

Exposure to sulphur mustard (SM) gas may have extensive immediate effects on the respiratory system. However, long-term effects are far less known. This case report describes a Kurdish male child who was exposed to SM gas during a chemical attack in Iraq at 5 yrs of age. In the acute phase, the child developed severe respiratory symptoms with a chemical pneumonia. Extensive burning of the skin occurred. In the course of 10 yrs, lung function deteriorated progressively to a forced expiratory volume in one second of 30% of predicted value. Severe air-trapping occurred. The lung function abnormalities were not reversed by treatment with corticosteroids or bronchodilators. Infectious exacerbations of the child's lung disease occurred. High resolution computed tomography scan showed multiple bronchiectasis. The histological picture of an open lung biopsy was best described as a "chronic bronchiolitis".

Exhaled breath condensate (EBC) is a rapidly growing field of research in respiratory medicine. Airway inflammation is a central feature of chronic lung diseases, like asthma, cystic fibrosis, bronchopulmonary dysplasia and primary ciliary dyskinesia. EBC may be a useful technique for non-invasive assessment of markers of airway inflammation. The non-invasive character of EBC "inflammometry" and the general lack of appropriate techniques makes it particularly interesting for paediatrics. We provide a detailed update on the methods currently used for EBC collection and measurement of mediators. We emphasize on paediatric data. The apparent simplicity of the EBC method must not be overstated, as numerous methodological pitfalls have yet to overcome. Comparison and interpretation of data on this rapidly growing field of research is mainly hampered by the lack of standardization and the lack of specific high-sensitivity immunochemical or colorimetric assays. The initiative of the European Respiratory Society to institute a task force on this topic is a first step towards a uniform technique of EBC. Meanwhile, when using this technique or when interpreting research data, one should be fully aware of the possible methodological pitfalls.

There are limited data on health-related quality of life (HRQoL) changes over time in children with cystic fibrosis (CF). We investigated associations between clinical and treatment variables with changes in HRQoL during 1 year. Forty-nine children with CF aged 6-18 years were followed in this multicentre, observational cohort study during 1 year. HRQoL was measured by the validated disease specific cystic fibrosis questionnaire-revised (CFQ-R). The CFQ-R total score as well as most domain scores improved significantly (8.0 points and [3.3-31.7] points respectively) during the one-year follow-up. Age at baseline demonstrated a strong longitudinal association with the change of CFQ-R total score (2.853 points decrease of CFQ-R total score per year increase in age) and several domain scores. Below 12 years of age, CFQ-R total score improved in most children, whereas a deterioration was observed in most children above 12 years. The number of PEx was associated with an increase of treatment burden score (4.466 points decrease per extra PEx).CONCLUSION: In the group as a whole, HRQoL improved significantly over time. However, changes over time were significantly influenced by age: below 12 years of age, HRQoL improved in most patients whereas a deterioration was observed in most children >12 years. Strategies how to preserve or ideally to improve HRQoL in adolescence should be developed. What is known: • Quality of life in patient with CF is diminished • Although CF is a chronic disease, longitudinal data on QoL in children with CF are scarce. What is new: • Below 12 years of age, quality of life improved in most children during the 1-year follow-up whereas a deterioration in quality of life was observed in most children above 12 years. • the treatment burden score of QoL correlated with the exacerbation rate.

Wheezing is one of the most common respiratory symptoms in preschool children under six years old. Currently, no tests are available that predict at early stage who will develop asthma and who will be a transient wheezer. Diagnostic tests of asthma are reliable in adults but the same tests are difficult to use in children, because they are invasive and require active cooperation of the patient. A non-invasive alternative is needed for children. Volatile Organic Compounds (VOCs) excreted in breath could yield such non-invasive and patient-friendly diagnostic. The aim of this study was to identify VOCs in the breath of preschool children (inclusion at age 2-4 years) that indicate preclinical asthma. For that purpose we analyzed the total array of exhaled VOCs with Gas Chromatography time of flight Mass Spectrometry of 252 children between 2 and 6 years of age. Breath samples were collected at multiple time points of each child. Each breath-o-gram contained between 300 and 500 VOCs; in total 3256 different compounds were identified across all samples. Using two multivariate methods, Random Forests and dissimilarity Partial Least Squares Discriminant Analysis, we were able to select a set of 17 VOCs which discriminated preschool asthmatic children from transient wheezing children. The correct prediction rate was equal to 80% in an independent test set. These VOCs are related to oxidative stress caused by inflammation in the lungs and consequently lipid peroxidation. In conclusion, we showed that VOCs in the exhaled breath predict the subsequent development of asthma which might guide early treatment.

Poly-ostotic Langerhans Cell Histiocytosis (LCH) can be difficult to distinguish clinically and histologically from disseminated infection in manifesting specific subtypes of Mendelian Susceptibility to Mycobacterial Disease (MSMD). In MSMD-patients, dominant negative germline mutations in the IFN-gamma R1 gene, in particular in exon 6, lead to autosomal dominant IFN-gamma receptor 1 deficiency (ADIFNGR1) and can mimic LCH. We hypothesized that similar defects might underlie the pathogenesis of LCH.IFN-gamma R1 expression was immunohistochemically determined at disease onset in biopsies from 11 LCH-patients and four ADIFNGR1-patients. IFN-gamma R1 function was analyzed in 18 LCH-patients and 13 healthy controls by assessing the IFN-gamma-induced upregulation of Fc-gamma-receptor I (Fc gamma RI) expression on monocytes. Pro-inflammatory cytokine production was measured after stimulation of whole blood with LPS and IFN-gamma. Exon 6 of the IFN-gamma R1 gene was sequenced in 67 LCH-patients to determine whether mutations were present.IFN-gamma R1 expression was high in three LCH-affected biopsies, similar to ADIFNGR1-affected biopsies, but varied from negative to moderate in eight other LCH-affected biopsies. No functional differences in IFN-gamma signaling were detected between LCH-patients with active or non-active disease and healthy controls. No germline mutations in exon 6 of the IFN-gamma R1 gene were detected in any of the 67 LCH-patients.In contrast to ADIFNGR1-patients, IFN-gamma signaling is fully functional in LCH-patients. Either performed before, during or after treatment, these non-invasive functional assays can distinguish LCH-patients from ADIFNGR1-patients and thereby facilitate correct therapy regimens for patients with recurrent osteolytic lesions.