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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.

Background: Wheeze is a heterogeneous symptom in preschool children. At preschool age it is hard to predict whether symptoms will pass or persist and develop into asthma. Our objective is to prospectively study whether inflammatory markers in exhaled breath condensate (EBC) and pre- and post-bronchodilator interrupter resistance (Rint) assessed at preschool age, are associated with wheezing phenotypes at school age. Methods: Children (N = 230) were recruited from the Asthma DEtection and Monitoring (ADEM) study. At preschool age [mean (SE): 3.3 (0.1) yr], pre- and post-bronchodilator Rint was assessed. EBC was collected using a closed glass condenser. Inflammatory markers (IL-2, IL-4, IL-8, IL-10, sICAM) were measured using multiplex immunoassay. Wheezing phenotypes at 5 yr of age were determined based on longitudinal assessment. Children were classified as: never (N = 47), early-transient (N = 89) or persistent wheezers (N = 94). Results: Persistent wheezers had elevated levels of all interleukins at preschool age compared to children who never wheezed (p

Summary Background The efficacy of inhaled corticosteroids (ICS) varies among wheezing preschool children. Currently, it is not possible to predict which fraction of wheezing children will benefit from an ICS treatment. Objective We explored whether fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC) can predict an ICS response in preschool wheezers. Methods An 8-week ICS study (registered at Clinicaltrial.gov: NCT 00422747; 200 μg; beclomethasone extra-fine daily) was performed in 93 wheezing children (age range 2.0–4.4 years). At baseline, FeNO was determined off-line. EBC was collected using a closed glass-condenser. The acidity of EBC was determined and other EBC markers [interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, soluble intercellular adhesion molecule, interferon-γ, eotaxin] were measured using a multiplex immunoassay. The change in airway resistance (Rint) and symptom score following ICS treatment was related to atopy (positive Phadiatop Infant test), FeNO and EBC markers. Results Airway resistance and symptoms mildly improved after ICS treatment [median (IQR): 1.4 (1.2–1.7) to 1.3 (1.1–1.5) kPa s/L, symptom score: 26 (23–28) to 28 (24–29), P

Background Allergen exposure is one of the environmental factors seemingly associated with the development of asthma. If asthma is a multi-factorial disease, it is hypothesised that prevention might only prove effective if most or all relevant environmental factors are simultaneously avoided. Objectives To assess effect(s) of monofaceted and multifaceted interventions compared with control interventions in preventing asthma and asthma symptoms in high risk children. Search strategy We searched the Cochrane Airways Trials Register (December 2008). Selection criteria Randomised controlled trials of allergen exposure reduction for the primary prevention of asthma in children. Interventions were multifaceted (reducing exposure to both inhalant and food allergens) or monofaceted (reducing exposure to either inhalant or food allergens) Follow up had to be from birth (or during pregnancy) up to a minimum of two years of age. Data collection and analysis We included in the analysis studies assessing the primary outcome (current diagnosis: asthma) and/or one of the secondary outcomes (current respiratory symptoms: wheezing, nocturnal coughing and dyspnoea). We pooled multifaceted and monofaceted intervention trials separately. We made an indirect comparison of their effects using tests for interaction to calculate relative odds ratios. Main results We included three multifaceted and six monofaceted intervention studies (3271 children). Physician diagnosed asthma in children less than five years, and asthma as defined by respiratory symptoms and lung function criteria in children aged five years and older, both favoured treatment with a multifaceted intervention compared to usual care ( 5 years: OR 0.52, 95% CI 0.32 to 0.85). However, there was no significant difference in outcome between monofaceted intervention and control interventions ( 5 years: OR 0.83, 95% CI 0.59 to 1.16). Indirect comparison between these treatments did not demonstrate a significant difference between multiple interventions and mono-interventions in reducing the frequency of asthma diagnosis in children under five years (relative OR 0.64 (95% CI 0.40 to 1.04, P = 0.07) or five years and older (relative OR 0.63, 95% CI 0.35 to 1.13, P = 0.12). There was also no significant difference between either mono- and multifaceted intervention and control in reducing the likelihood of symptoms of nocturnal coughing at follow up. Wheezing, however, showed a significant difference between multifaceted and mono-interventions (relative OR 0.59, 95% CI 0.35 to 0.99, P = 0.04), but the significance was lost when data on treatment only was analysed. Authors' conclusions The available evidence suggests that the reduction of exposure to multiple allergens compared to usual care reduces the likelihood of a current diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono-intervention studies have not produced effects which are statistically significant compared with control. In children who are at risk of developing childhood asthma, multifaceted interventions, characterised by dietary allergen reduction and environmental remediation, reduce the odds of a physician diagnosis of asthma later in childhood by half. This translates to a number needed to treat (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze was inconsistent and had no significant impact on nocturnal coughing or dyspnoea. Data from monofaceted intervention exposed children studies were not significantly different from those of control groups for all outcomes. There remains uncertainty as to whether multiple interventions are more effective than mono-component interventions. The comparisons made were indirect, making the conclusions drawn uncertain. To our knowledge there are no ongoing studies in which both intervention strategies are randomly compared. The findings, however, warrant further direct comparison between multiple- and monofaceted interventions aimed at reducing the prevalence of asthma in children. Plain Language Summary Mono and multifaceted allergen reducing interventions for the primary prevention of asthma in children at high risk of developing asthma It is possible that early exposure to allergens (substances which cause allergy) may lead to development of asthma in high risk children. This review asks whether the risk of developing asthma, which is a disease caused by many factors, can be decreased by reducing single allergen levels in children with genetic susceptibility, or whether the reduction of more than one type of allergen exposure simultaneously will lead to a better outcome. As a direct comparison could not be made using current research we made indirect comparisons using trials that had compared single or multiple interventions with a control. In children who are at risk of developing childhood asthma 'multifaceted' interventions, which involve both dietary allergen reduction and environmental change to reduce exposure to inhaled allergens, reduce the odds of a doctor diagnosing asthma later in childhood by half. However, the effect of these multifaceted interventions on wheeze reported by parents was inconsistent and there was no beneficial effect on night-time coughing or breathlessness. Single ('monofaceted') interventions were not significantly more effective than controls in the reduction of all outcomes, but there remains uncertainty as to whether multiple interventions are more effective than single component interventions.

Cystic fibrosis (CF) lung disease is characterized by chronic airway inflammation and recurrent infections, resulting in (ir)reversible structural lung changes and a progressive decline in lung function. The objective of this study was to investigate the relationship between non-invasive inflammatory markers (IM) in exhaled breath condensate (EBC), lung function indices and structural lung changes, visualized by high resolution computed tomography (HRCT) scans in CF. In 34 CF patients, lung function indices (forced expiratory volume in 1 s, forced vital capacity [FVC], residual volume, and total lung capacity [TLC]) and non-invasive IM (exhaled nitric oxide, and condensate acidity, nitrate, nitrite, 8-isoprostane, hydrogen peroxide, interferon-gamma) were assessed. HRCT scans were scored in a standardized and validated way, a composite score and component scores were calculated. In general, the correlations between non-invasive IM and structural lung changes, and between IM and lung function were low (correlation coefficients

Exhaled breath condensate (EBC) is a promising non-invasive method to assess respiratory inflammation in adults and children with lung disease. Especially in pre-school children, condensate collection is hampered by long sampling times because of open-ended collection systems. We aimed to assess the feasibility of condensate collection in pre-school children using a closed glass condenser with breath recirculation system, which also collects the residual non-condensed exhaled breath, and subsequently recirculates it back into the condenser. Condensate was collected before and after breath recirculation in 70 non-sedated pre-school children with and without recurrent wheeze. Cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-alpha) were measured in 50 mu l samples using ultrasensitive multiplexed liquid bead array. The success rate of condensate collection increased from 64% (without recirculation) to 83% (after breath recirculation), and mean condensate volume from 214 to 465 mu l respectively. Detection of cytokines was successful in 95-100% of samples. Cytokine concentrations before and after breath recirculation were not different (p > 0.232). In asthmatic children, only TNF-a concentrations were significantly decreased, compared to non-asthmatics. In pre-school children, the collection of EBC is feasible using a new closed glass condenser with breath recirculation system. This new method may help to assess - non-invasively - cytokine profiles in asthmatic and non-asthmatic pre-school children.

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: Airway inflammation in asthma is characterized by the production of cytokines, chemokines and soluble adhesion molecules. The assessment of these inflammatory biomarkers in exhaled breath condensate (EBC) is hampered by low detection rates. However, the use of a glass condenser system combined with a sensitive analytical technique may increase the possibility to assess these biomarkers in EBC in a reliable way. OBJECTIVE: (1) To assess the detection rates of cytokines (IL-1alpha, -1beta, -2, -4, -5, -6, -10, -12p70, -13, -18, IFN-gamma, TNF-alpha), chemokines [MIP1alpha (CCL3), MIF, eotaxin (CCL11), RANTES (CCL5), IP10 (CXCL10), IL8 (CXCL8), MCP1] and soluble adhesion molecules [soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM)] in EBC of children with asthma and healthy control children; (2) To study the differences in the biomarker concentration between children with asthma and controls. METHODS: Sixty children were included: 31 asthmatics (71% atopic) and 29 controls. Exhaled breath condensate was collected using a glass condenser system. The inflammatory markers (IM) were analysed using multiplex immunoassay technology. RESULTS: Detection percentages of cytokines, chemokines and adhesion molecules ranged from 94% to 100%, except for eotaxin (CCL11) and RANTES (CCL5) (detection rates of 10% and 45% in healthy controls, respectively). The intra-subject variability of biomarkers in EBC in the group as a whole ranged from 5.2% to 35.0%. In asthmatics, the levels of cytokines (IL-2, -4, -5, -6, -13, IFN-gamma), chemokines (MIP1alpha [CCL3], MIF, RANTES [CCL5], IP10 [CXCL10], IL8 [CXCL8], MCP1) and adhesion molecules (sICAM, sVCAM) were significantly increased in comparison with controls (P

A 3-yr-old female presented at the emergency dept with a 24-h history of dyspnoea, productive cough, bilious vomiting and a low-grade fever. At physical examination, nasal flaring and mild chest retractions were noted. No stridor or wheezing was present and oxygen saturation was normal. Heart rate was 120 bpm in the presence of a low-grade fever (38.6°C). Decreased breath sounds were heard over the right hemithorax, while no asymmetry was noted on either chest inspection or percussion. Otherwise, the findings of physical examination were normal. Laboratory investigation showed no signs of infection. A chest radiograph was performed (fig. 1⇓). As a result of the dyspnoea, the patient was admitted and azithromycin was commenced to cover possible Mycoplasma pneumoniae . However, serological screening for Mycoplasma antibodies was negative. Furthermore, no pathogen was cultured from either blood or pharynx. Fig. 1— Chest radiograph at presentation. During admission an additional history was taken, in which the mother reported that the child had previously choked upon eating a piece of candy, 1 week before the onset of symptoms. To rule out the presence of a foreign body, which could explain both the symptoms and the abnormalities seen on chest radiography, the patient was transferred to a tertiary centre for bronchoscopic evaluation. At bronchoscopy, purulent sputum was noted in the left main bronchus but no foreign body was found. Laboratory investigation was repeated, showing C-reactive protein (CRP) of 16 mg·L−1 without any other abnormalities. Moraxella catarrhalis was cultured from the sputum obtained at bronchoscopy. This pathogen was treated with amoxicillin and clavulanic acid for 7 days, although no clear signs of infection were demonstrated. As no explanation for the clinical situation was found, computed tomography (CT) of the chest was performed 5 days after admission (fig. 2⇓). Fig. 2— Non-contrast-enhanced computed tomography scan of the chest in a pulmonary window setting. Additional …

Item does not contain fulltext BACKGROUND: The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections. OBJECTIVE: To investigate the relation between early intestinal viral infections in relation to the development of atopic symptoms (eczema, wheeze and atopic sensitization) in the first and second year(s) of life. METHODS: In the KOALA Birth Cohort Study, we assessed IgG seropositivity for rota- and norovirus (GGI.1 and GGII.4) at 1 year of age. This was related to allergic sensitization [specific immunoglobulin E (IgE)] at 1 and 2 years, and parent reported eczema and wheeze in the first 2 years, using logistic regression analysis adjusted for confounders. RESULTS: Rotavirus seropositivity (39%) was associated with an unexpected higher risk of recurrent wheeze in the first and second year of life [adjusted odds ratio (OR) 3.1 and 95% confidence intervals (CI) 1.1-9.1] and persistent and new recurrent wheeze (adjusted OR 2.7 and 95% CI 1.1-6.2). No further associations were found between intestinal viral seropositivity and atopic manifestations. CONCLUSION: Our data did not show a clear protection by enteric viral infections in young children on development of IgE response to allergens, but rotavirus infection in the first year was a risk factor for wheeze. However, this needs to be followed up to older ages in order to establish the true importance of intestinal viral infections and especially cumulative effects in AD aetiology. Exposure to rotavirus may offer a new and interesting focus on infant wheeze and later asthma development.

BACKGROUND: Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma. OBJECTIVE: To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC). METHODS: In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period. RESULTS: Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment. CONCLUSION: The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma.

Optimal collection and analysis of exhaled breath condensate (EBC) are prerequisites for standardisation and reproducibility of assessments. The present study aimed to assess reproducibility of EBC volume, hydrogen peroxide (H(2)O(2)), 8-isoprostane and cytokine measurements using different condensers, including a newly developed glass condenser. At four points in time, 30 healthy subjects performed sequential EBC collections randomly using the following four condensers: glass, silicone, EcoScreen (Erich Jaeger GmbH, Hoechberg, Germany) and an optimised glass condenser. In small EBC samples, H(2)O(2) was measured by spectrophotometer, 8-isoprostane by enzyme immunoassay, and cytokines by multiplexed xMAP technology (Luminex Corporation, Austin, TX, USA). The optimised glass condenser yielded significantly more EBC volume (median 2,025 microL, interquartile range 1,600-2,525). The reproducibility of EBC volume, yielded by the new glass condenser, was comparable with EcoScreen (19-20 coefficients of variation (CV)%), but was significantly better compared with silicone and glass (29-37 CV%). The new condenser was associated with significantly more detections of H(2)O(2), 8-isoprostane, interleukin-2, -4, -5 and -13, and tumour necrosis factor-alpha. Isoprostane concentrations were significantly higher using the new condenser, whereas H(2)O(2) and cytokine concentrations were not. Reproducibility of biomarkers was equally variable for all condenser types. In conclusion, significantly more exhaled breath condensate volume and biomarker detections were found using the optimised glass condenser, including higher 8-isoprostane levels. However, biomarker reproducibility in exhaled breath condensate in healthy adults was not influenced by the type of condenser.

BACKGROUND: Exhaled nitric oxide and inflammatory biomarkers in exhaled breath condensate may be useful to diagnose and monitor childhood asthma. Their ability to indicate an asthma diagnosis, and to assess asthma severity and control, is largely unknown. OBJECTIVE: To study (1) the ability of exhaled nitric oxide and inflammatory markers in exhaled breath condensate (nitrite, nitrate, hydrogen peroxide, 8-isoprostane, IFN-gamma, TNF-alpha, IL-2, -4, -5, -10 and acidity) to discriminate between childhood asthma and controls. (2) The ability of these biomarkers to indicate asthma severity and control. METHODS: One-hundred and fourteen children were included: 64 asthmatics (10.7+/-3.0 years, 67.2% atopic) and 50 controls (10.0+/-0.4 years). Condensate was collected using a glass condenser. RESULTS: Exhaled nitric oxide, IFN-gamma and IL-4 in exhaled breath condensate differed significantly between asthma and controls. Multivariate backward logistic regression models demonstrated that IL-4 (odds ratio 7.9, 95% confidence interval 1.2-51.0) was the only significant indicator of an asthma diagnosis. Asthma control was best assessed by exhaled nitric oxide, 8-isoprostane, IFN-gamma and IL-4 (sensitivity 82%, specificity 80%, P

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: Exacerbations are an important source of disability, symptoms, loss of quality of life and lung function, and high costs of care in patients with cystic fibrosis (CF). Purpose: the aim was to assess the ability of noninvasive inflammation markers in exhaled breath to predict exacerbations in children with CF. Methods: 49 children with CF aged 5-18 years were prospectively followed during one year. At 2 month-intervals, the following parameters were assessed: 1) lung function (forced expiratory volume in one second [FEV1] and forced vital capacity [FVC]) according to ERS/ATS standards; 2) exhaled breath condensate (EBC) was sampled and TNF-alpha, macrophage inhibiting factor (MIF), interleukin-6 (IL-6) and IL-8 were analysed; 3) 1 liter of exhaled breath was stabilized on carbon desorption tubes, and volatile organic compounds (VOCs) profiles were analyzed by gaschromotography time-of-flight mass spectrometry (GC-TOF-MS); Results: The mean age was 10.3 years, and the mean FEV1 was 89,6% of predicted value. 17 of the 49 patients experienced no exacerbations (=35%) , whereas 32 children got one or more exacerbations. Markers in EBC predicted 55% of the exacerbations correctly (sensitivity 70%, specificity 50%, 9conditionally specified models9). A combination of 9 most predictive VOCs was able to predict 79% of exacerbations correctly (sensitivity 81%, specificity 82%), provided that the time between the exhaled breath sampling and onset of exacerbations was not longer than 1 week. Conclusion: CF exacerbations were best predicted by a set of 9 VOCs in exhaled breath, provided that the time interval between breath sampling and exacerbations was not longer than 7 days.

Background: Asthma control falls short of current goals of asthma management guidelines. Non-invasive monitoring of airway inflammation may help to improve the level of asthma control in children. Aim: 1) To identify a set of exhaled volatile organic compounds (VOCs) that is most predictive for an asthma exacerbation in children. 2) To determine the chemical background of predictive VOCs. Methods: In an one-year prospective observational study, 96 asthmatic children were studied . At clinical visits with an interval of 2 months, asthma control, fractional exhaled nitric oxide, lung function (FEV 1 , FEV 1 /VC) and VOCs in exhaled breath by means of gas chromatography time-of-flight mass spectrometry, were determined. Random Forrest classification modeling was used to select predictive VOCs, followed by building of receiver operating characteristic-curves (ROC-curves). Results: An inverse relation between the predictive power of a set of VOCs and time between sampling of exhaled breath and the onset of an exacerbation was found. The sensitivity and specificity of the model predicting exacerbations 14 days after sampling were 88% and 75%, respectively. The area under the ROC-curve was 90%. The sensitivity for prediction of asthma exacerbations within 21 days after sampling was 63%. In total, 7 VOCs were selected for the classification model: 3 aldehydes, 1 hydrocarbon, 1 ketone, 1 aromatic compound, and 1 undefined VOC. Conclusion: VOCs in exhaled breath showed potential to predict asthma exacerbations in children within 14 days after sampling. Before use in clinical practice, the validity to predict asthma exacerbations should be studied in a larger cohort.

Rationale: A reliable asthma diagnosis is difficult in wheezing preschool children. Objectives: To assess whether exhaled biomarkers, expression of inflammation genes, and early lung function measurements can improve a reliable asthma prediction in preschool wheezing children. Methods: 202 preschool recurrent wheezers (aged two-four years) were prospectively followed-up until age six years. At age six, a diagnosis (asthma or transient wheeze) was based on symptoms, lung function and asthma medication use. The added predictive value (area under the receiver operating characteristic curve [AUC]) of biomarkers to clinical information (assessed with the Asthma Predictive Index [API]) assessed at preschool age, in diagnosing asthma at age six was determined with a validation set. Biomarkers in exhaled breath condensate [EBC], exhaled volatile organic compounds [VOCs], gene expression, and airway resistance were measured. Measurements and Main Results: At age six, 198 children were diagnosed (76 asthmatics, 122 transient wheezers). Information on exhaled VOCs significantly improved asthma prediction (AUC: 89% (increase of 28%), positive predictive value (PPV)/negative predictive value (NPV) 82/83%) which persisted in the validation set. Information on expression of toll-like receptor 4, catalase and tumor-necrosis-factor alpha significantly improved asthma prediction (AUC: 75% (increase of 17%), PPV/NPV 76/73%). This could not be confirmed after validation. Biomarkers in EBC and airway resistance (pre- and post- bronchodilator) did not improve an asthma prediction. The combined model with VOCs, gene expression and API had an AUC of 95% (PPV/NPV 90/89%). Conclusions: Adding information on exhaled VOCs and possibly expression of inflammation genes to the API significantly improves an accurate asthma diagnosis in preschool children.

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

BACKGROUND: Inflammatory mediators in exhaled breath condensate (EBC) indicate ongoing inflammation in the lungs and might differentiate between asthma and cystic fibrosis (CF). OBJECTIVES: To evaluate the presence, concentration, and short-term variability of TH1- and TH2-mediated cytokines (interferon-gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], interleukin 10 [IL-10], IL-5, IL-4, and IL-2) in EBC of children with asthma or CF and in controls and to analyze the discriminating ability of inflammatory markers in EBC between children with asthma or CF and controls. METHODS: Expired air was conducted through a double-jacketed glass tube cooled by circulating ice water. In 33 asthmatic children, 12 children with CF, and 35 control children, EBC was collected during tidal breathing. Cytokines were measured using flow cytometry. RESULTS: Interleukin 2, IL-4, IFN-gamma, and IL-10 were detected in 16%, 16%, 11%, and 9%, respectively, of all samples in asthma and CF. Interleukin 5 and TNF-alpha were not detected in children with CF. Cytokine concentrations did not differ significantly in children with asthma vs CF. In controls, IFN-gamma, TNF-alpha, and IL-10 were detected in 9%, 14%, and 3%, respectively; IL-2, IL-4, and IL-5 were not detected in controls. CONCLUSIONS: Cytokines such as IFN-gamma, TNF-alpha, IL-10, IL-5, IL-4, and IL-2 can be detected in EBC of children with asthma or CF. However, the concentrations found are close to the detection limits of the assay used. These findings emphasize the importance of developing more sensitive techniques for the analysis of EBC and of standardizing the EBC collection method.

In past decades the prevalence of asthma in children has increased substantially but this trend seems not to have persisted into the twenty-first century. What might have caused the increased prevalence is not well understood. With the expectation that the prevalence may be decreased by reducing exposure to environmental factors, several birth cohort studies are being (or have been) carried out all over the world. Although many studies are still ongoing, decisions on data gathered by these studies will be of great importance for clinical practice. An overview of designs of available studies will be essential in constructing a metaanalysis. We describe the similarities and differences between designs and variable sets of birth cohort studies focusing on the relationship between allergen exposure (solely or in combination with other environmental exposures) and development of childhood asthma. We also evaluate which studies are particularly qualified for inclusion in a meta-analysis relating asthma preventi...

The PREVASC study addresses the primary prevention of asthma in infants and small children. The objective of this study is to investigate whether a multifaceted prenatally started intervention strategy in high-risk infants leads to a decrease in the occurrence of (severe) asthma and whether a refinement of the prevention strategy leads to an increase in the adherence to the prevention program. The primary prevention program includes house dust mite impermeable bed coverings, education on breast feeding, hypoallergenic feeding, timing of introduction of solid food and smoking cessation. A total of 888 infants were prenatally included. By the time of inclusion the mothers were 3-7 months pregnant. About 27 infants were excluded from the study and 18 dropped out. Of the remaining 843 infants 535 had a first-degree familial predisposition of asthma (high-risk group), whereas a reference group of 308 (162 boys) infants was not predisposed for asthma in the first-degree (low-risk group). To evaluate the (cost-)effectiveness of the preventive intervention, 222 (118 boys) infants of the high-risk group allocated to the intervention group and 221 (112 boys) allocated to a control group are followed up. The low-risk infants served as controls to evaluate the predictive value of high risk (first-degree familial predisposition of asthma). The infants are followed from the prenatal stage until they reach the age of 6 yr. The remaining 92 high-risk infants were included in an optimized randomized-clinical adherence trial (RCAT). Of these 92 infants, 45 (20 boys) were allocated to an intervention group and 47 (24 boys) to a control group. Until now all infants have been followed for at least 1 yr.

Contains fulltext : 59248.pdf (Publisher’s version ) (Closed access) BACKGROUND: Compliance to and the effect of pre- and post-natal exposure reduction measures to prevent asthma in high-risk children from asthmatic families were studied. METHOD: Families were randomized to a special care group (n=222) and a control group (n=221). Educational advice on measures to reduce their newborn's exposure to allergens and smoke was provided to the special care group during three visits (two pre-natal and one post-natal). The control group (n=221) received usual care. RESULT: After the intervention, the special care group differed significantly (P

Exhaled markers of airway inflammation become increasingly important in the management of childhood asthma. The aims of the present study are: 1) to compare exhaled markers of inflammation (nitric oxide, carbon monoxide, and acidity of breath condensate) with conventional asthma measures (lung function tests and asthma control score) in childhood asthma; and 2) to investigate the detectability of albumin, CRP, IL-6, IL-8, TNF-alpha, sICAM-1, and sTNF-R75 in the exhaled breath condensate (EBC) of asthmatic children. Thirty-two children with mild to moderate persistent asthma and healthy controls aged 6-12 years were studied. We measured exhaled NO and CO, and subsequently EBC was collected. Inflammatory mediators in EBC were measured using an enzyme-linked immunosorbent assay. Respiratory symptoms and asthma control were assessed using the asthma control questionnaire (ACQ) of Juniper et al. (Eur Respir J 1999;14:902-907). Exhaled NO showed a significant correlation with exhaled CO (r = 0.59, P < 0.05) and FEV1 (r = -0.59, P < 0.05), but not with ACQ score (r = 0.48, P = 0.06). Exhaled CO was correlated with prebronchodilator FEV1 (r = -0.45, P < 0.05), but not with asthma control (r = 0.18, P = 0.35). Acidity of EBC was significantly lower in asthmatic children than in healthy controls (P < 0.05), but did not correlate with any of the conventional asthma measures. We were not able to demonstrate the presence of CRP, IL-6, IL-8, TNF-alpha, sICAM-1, and sTNF-R75 in EBC. Albumin was found in two EBC samples of asthmatic children. We conclude that exhaled NO had a better correlation with lung function parameters and asthma control than exhaled CO and acidity of EBC, in mild to moderate persistent childhood asthma. However, exhaled NO, CO, and deaerated pH of EBC did not differ between asthmatic children and controls, possibly because of a too homogeneous and well-controlled study population. To further evaluate the clinical utility of exhaled markers in monitoring childhood asthma, more studies are required on a wider range of asthma severity, and preferably with repeated measurements of markers and of asthma control.

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.

Item does not contain fulltext BACKGROUND: When analyzing the effect of environmental exposure reduction measures on asthma in high-risk children, one must know how far asthmatic families already have applied such measures, because this would affect the effectiveness and efficiency of interventions aimed at reducing environmental exposure. OBJECTIVE: To describe the room for improvement by asthmatic families in mite, pet, and food allergen reducing measures and in parental passive smoking and to determine the resulting levels of mite and pet allergens by the applied sanitation measures. METHODS: Data were sampled by observation, weekly diary entries, and questionnaire when the infant was 6 months old and 1 year old. Dust samples were collected by vacuuming the living room floor and the parental and infant mattresses. Multiple logistic regression analyses were applied with the use of mattress encasing, having a smooth floor covering, having pets, exclusive breast-feeding and/or hypoallergenic formula during the infant's first 6 months, and passive smoking as the dependent variables. RESULTS: Frequencies of applied measures were as follows: having a smooth floor covering, 36%; daily house cleaning, 27%; use of parental and infant antimite mattress encasings, 13% and 9%, respectively; keeping no pets, 66%; no cow's milk-based regular formula, 13%; no solid foods in the first 6 months of life, 28%; and abstinence of smoking by the mother prenatally, 89%; by the mother postnatally, 85%; and by her partner, 76%. Having a smooth floor covering and daily cleaning but not use of antimite mattress encasings resulted in significantly lower mite and pet allergen levels. CONCLUSIONS: There is (still) enough room for improvement to reduce exposure to inhalant and food allergens, especially by application of mattress encasings, exclusive breast-feeding and/or hypoallergenic formula feeding, and postponing the time until first solids are given.

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.

Cite this as: E. Dompeling and Q. Jobsis, Clinical & Experimental Allergy, 2011 (41) 299-301.

Wheezing in preschool children is a very common symptom. An adequate prediction of asthma in these children is difficult and cannot be reliably assessed with conventional clinical tools. The study of potential predictive biomarkers in various media, ranging from invasive sampling (e.g. bronchoscopy) to non-invasive sampling (lung function testing and exhaled breath analysis) was comprehensively reviewed. The evolution in biomarker discovery has resulted in an 'omics' approach, in which hundreds of biomarkers in the field of genomics, proteomics, metabolomics and 'breath-omics' can be simultaneously studied. First results on gene expression and exhaled breath profiles in predicting an early asthma diagnosis are promising. However, many hurdles need to be overcome before clinical implementation is possible. In order to reliably predict asthma in a wheezing child, probably a holistic approach is needed, combining clinical information with blood sampling, lung function tests, and potentially exhaled breath analysis. The further development of predictive, non-invasive biomarkers may eventually improve an early asthma diagnosis in wheezing preschool children, and assist clinicians in early treatment decision-making. This article is protected by copyright. All rights reserved.

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.

Background Asthma remains poorly controlled in children. Home monitoring of asthma control may help to improve the level of asthma control. Objectives To compare 2 methods to assess asthma control: (1) prospective home monitoring, based on daily assessment of forced expiratory volume in 1 second (FEV 1 ) and electronic symptom score, and (2) Asthma Control Questionnaire (ACQ) with retrospective assessment of symptoms and FEV 1 . Methods Ninety-six children with asthma were prospectively followed up during 1 year. Asthma control was assessed by home monitoring, including an electronic symptom score based on Global Initiative for Asthma (GINA) criteria and FEV 1 measurements. In the hospital, the ACQ was completed and FEV 1 was measured. Kappa analysis was performed to assess levels of agreement between the 2 methods. Results Agreement between the 2 methods was low (κ coefficient of 0.393). In 29 children (37%), prospective home monitoring was less optimistic than the retrospective assessment of asthma control by the ACQ. Conclusion This study found low agreement between asthma control based on GINA criteria by means of prospective home monitoring and the hospital ACQ. The prospective home monitor detected more cases of less well-controlled asthma than the ACQ. However, optimization of adherence to home monitor use is necessary. Trial Registration clinicaltrials.gov Identifier: NCT01239238.

BACKGROUND: A significant number of parents are unaware or unconvinced of the health consequences of passive smoking (PS) in children. Physicians could increase parental awareness by giving personal advice. AIM: To evaluate the current practices of three Dutch health professions (paediatricians, youth health care physicians, and family physicians) regarding parental counselling for passive smoking (PS) in children. METHODS: All physicians (n = 720) representing the three health professions in Limburg, The Netherlands, received an invitation to complete a self-administered electronic questionnaire including questions on their: sex, work experience, personal smoking habits, counselling practices and education regarding PS in children. RESULTS: The response rate was 34%. One tenth (11%) of the responding physicians always addressed PS in children, 32% often, 54% occasionally and 4% reported to never attend to it. The three health professions appeared comparable regarding their frequency of parental counselling for PS in children. Addressing PS was more likely when children had respiratory problems. Lack of time was the most frequently mentioned barrier, being very and somewhat applicable for respectively 14% and 43% of the physicians. One fourth of the responders had received postgraduate education about PS. Additionally, 49% of the responders who did not have any education about PS were interested in receiving it. CONCLUSIONS: Physicians working in the paediatric field in Limburg, The Netherlands, could more frequently address PS in children with parents. Lack of time appeared to be the most mentioned barrier and physicians were more likely to counsel parents for PS in children with respiratory complaints/diseases. Finally, a need for more education on parental counselling for PS was expressed.

Objective Obesity has been identified as a risk factor for asthma in children. However, in the Netherlands, the obesity prevalence is rising while the asthma prevalence in children is stabilising. The aim of this study is to clarify the association between asthma and Body Mass Index (BMI) in children and whether this association is influenced by sex. Study Design Parents of 39,316 children (6-16 years) in the south of the Netherlands were invited to complete an online questionnaire on respiratory symptoms, anthropometric variables and several potential confounding factors for asthma and obesity (including sex, birth weight and breastfeeding). Data was analysed by multivariable logistic regression models and an ordinal regression model. Results The response rate was 24% (n boys= 4,743, n girls= 4,529). The prevalence of asthma, overweight and obesity was 8%, 15% and 2% respectively. Body mass index - standard deviation Score (BMI-SDS) was related to current asthma (adjusted OR: 1.29; 95%CI: 1.14-1.45, p≤0.001). When stratified for sex, asthma and BMI-SDS were only related in girls (Girls: adjusted OR: 1.31; 95%CI: 1.13-1.51, p≤0.001. Boys: adjusted OR: 1.01; 95%CI: 0.91-1.14, p=0.72). Conclusions The positive association between BMI-SDS and asthma is only present in girls, not boys. Future studies into obesity and asthma should correct for sex in their analyses.

Objectives: The approved methods for sweat testing, Gibson-Cooke Pilocarpine Iontophoresis (GCQPIT) or the Wescor Macroduct® Sweat Test system, have many steps that can and do lead to errors. The GCQPIT method is 54 years old, was never intended for newborns, has scared parents and burned infants. Thus, there is a critical need to improve sweat testing technology. Methods: The CF Quantum® Sweat Test (CFQT) System consists of: a. a controller and electrode set that is worn on the arm for pilocarpine iontophoresis; b. a chloride test patch that collects the sample. Chloride ions in the sweat sample come into contact with silver chromate in the test patch, and an ion exchange reaction occurs which creates silver chloride, an insoluble white precipitate formed in the center of the patch; c. a CF Analyzer utilizes a camera and proprietary software that scans the reacted chloride test patch and calculates the concentration of chloride and volume of sweat collected. Herein are preliminary results of a multicenter study. Patients with a previous diagnosis of CF or referred to the sweat testing lab had bilateral GCQPIT or Macroduct® and bilateral CFQT tests performed. Thus far, 57 subjects with a known diagnosis of CF and 56 subjects referred to the sweat test lab have had both tests performed. There is excellent agreement of sweat chloride values between GCQPIT/Macroduct® and CFQT with a Pearson correlation coefficient of r = 0.97. In a post-test questionnaire, 85% of parents/patients preferred the CFQT. Conclusion: The CFQT yields sweat chloride values that are equivalent to that of GCQPIT/Macroduct sweat testing. Supported by: Legacy of Angels Foundation, PolyChrome Medical, Inc.

Background In children, the prevalence’s of both obesity and asthma are disconcertingly high. Asthmatic children with obesity are characterised by less asthma control and a high need for asthma medication. As the obese asthmatic child is becoming more common in the clinical setting and the disease burden of the asthma-obesity phenotype is high, there is an increasing need for effective treatment in these children. In adults, weight reduction resulted in improved lung function, better asthma control and less need for asthma medication. In children this is hardly studied. The Mikado study aims to evaluate the effectiveness of a long term multifactorial weight reduction intervention, on asthma characteristics in children with asthma and a high body weight. Methods/design The Mikado study is a two-armed, randomised controlled trial. In total, 104 participants will be recruited via online questionnaires, pulmonary paediatricians, the youth department of the Municipal Health Services and cohorts of existing studies. All participants will be aged 6–16 years, will have current asthma, a Body Mass Index in the overweight or obesity range, and no serious comorbidities (such as diabetes, heart diseases). Participants in the intervention arm will receive a multifactorial intervention of 18 months consisting of sessions concerning sports, parental involvement, individual counselling and lifestyle advices including dietary advices and cognitive behavioural therapy. The control group will receive usual care. The primary outcome variables will include Forced Expiratory Volume in one second and Body Mass Index - Standard Deviation Score. Secondary outcomes will include other lung function parameters (including dynamic and static lung function parameters), asthma control, asthma-specific quality of life, use of asthma medication and markers of systemic inflammation and airway inflammation. Discussion In this randomised controlled trial we will study the potential of a multifactorial weight reduction intervention to improve asthma-related outcome measures in asthmatic children with overweight. Moreover, it will provide information about the underlying mechanisms in the relationship between asthma and a high body weight in children. These findings can contribute to optimal management programs and better clinical guidelines for children with asthma and overweight. Trial registration Clinicaltrial.gov NCT00998413

Background Especially children at risk for asthma are sensitive to the detrimental health effects of passive smoke (PS) exposure, like respiratory complaints and allergic sensitisation. Therefore, effective prevention of PS exposure in this group of vulnerable children is important. Based on previous studies, we hypothesized that an effective intervention program to prevent PS exposure in children is possible by means of a motivational interviewing tailored program with repeated contacts focussing on awareness, knowledge, beliefs (pros/cons), perceived barriers and needs of parents, in combination with feedback about urine cotinine levels of the children. The aim of the PREPASE study is to test the effectiveness of such an intervention program towards eliminating or reducing of PS exposure in children at risk for asthma. This article describes the protocol of the PREPASE study. Methods The study is a one-year follow-up randomized controlled trial. Families with children (0–13 years of age) having an asthma predisposition who experience PS exposure at home are randomized into an intervention group receiving an intervention or a control group receiving care as usual. The intervention is given by trained research assistants. The intervention starts one month after a baseline measurement and takes place once per month for an hour during six home based counselling sessions. The primary outcome measure is the percentage of families curtailing PS exposure in children (parental report verified with the urine cotinine concentrations of the children) after 6 months. The secondary outcome measures include: household nicotine level, the child’s lung function, airway inflammation and oxidative stress, presence of wheezing and questionnaires on respiratory symptoms, and quality of life. A process evaluation is included. Most of the measurements take place every 3 months (baseline and after 3, 6, 9 and 12 months of study). Conclusion The PREPASE study incorporates successful elements of previous interventions and may therefore be very promising. If proven effective, the intervention will benefit the health of children at risk for asthma and may also create opportunity to be tested in other population. Trial registration number NTR2632

Background: Two forms of environmental tobacco smoke (ETS) exposure have been described: second-hand smoke (SHS), which is the direct exposure to tobacco smoke; and third-hand smoke (THS), which is the exposure to residuals from tobacco smoke after the cigarette has been extinguished. The effects of SHS exposure on children’s respiratory health are known, but not of THS exposure. We evaluated the association between both exposures and respiratory complaints in children aged 0-13 years, and assessed whether the risk of respiratory complaints due to these exposures was higher in children with genetic predisposition for asthma compared to those without. Methods: A cross-sectional survey (91 items) was performed in 10,000 families with a child aged 0-13 years living in South-Limburg, the Netherlands, assessing child and family characteristics, child’s respiratory health, and parental smoking behaviour. Data were analyzed with (adjusted) multiple logistic regressions. Results: 1899 families responded. SHS exposure was not associated with an increased risk of respiratory complaints in children. THS exposure was associated with respiratory tract infections in the past 12 months (ORadjusted: 2.13; 95% CI: 1.04-4.36; p=0.04) and recent wheezing (ORadjusted: 2.61; 95%CI: 1.19-5.71; p=0.02) in children. There was no interaction between genetic predisposition for asthma and ETS exposure. Conclusions: Unlike previous studies, our study could not reveal a significant association between SHS exposure and an increased risk of respiratory complaints in children, most likely due to study limitations concerning cross-sectional design, response rate, selection bias and parental underreporting of SHS exposure to their children. THS exposure was significantly associated with an increased risk of respiratory complaints in children. This adds to the limited knowledge about the health effects of THS exposure in children and suggests that more research on this topic is needed. A genetic predisposition for asthma combined with ETS exposure did not increase the risk of respiratory complaints in children.

The aetiology of childhood asthma is complex. An early dysfunction in the immunological development of the innate immune system in combination with environmental factors possibly triggers asthma. CD14 and toll-like receptors are important components of the innate immune system. The aim of this systematic review was to obtain a better insight into the relation between CD14 and toll-like receptors and childhood asthma in Caucasians. We searched PubMed and EMBASE for relevant articles. In total, 44 articles were included. The quality of the selected studies was independently assessed by the first two authors using the Newcastle-Ottawa quality assessment scale. Toll-like receptor 2, toll-like receptor 6, toll-like receptor 9, and toll-like receptor 10 appear to have some association with childhood asthma in Caucasians. The evidence for a relation of CD14 with childhood asthma is limited. In conclusion, there is no convincing evidence yet for a role of CD14 and toll-like receptors in relation to childhood asthma. Future studies should include haplotype analysis and take environmental factors into account to further clarify the role of CD14 and toll-like receptors on childhood asthma.

Pancreatitis-associated protein (PAP) is currently discussed as a marker in newborn screening (NBS) for cystic fibrosis (CF). However, it is not known if PAP concentrations are influenced by sex, gestational age, birth weight, blood transfusion or time of collection and what this would mean for NBS for CF. In 2008 all newborns in part of the Netherlands were screened for CF by an IRT/PAP protocol. PAP concentration was determined by the MucoPAP ELISA (DynaBio), which was modified to a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) method following a protocol of PerkinElmer. In healthy newborns, the median PAP concentration was 0.5 mu g/l (Interquartile range (IQR 0.3-0.8) whereas this was 3.2 mu g/l (IQR 2.0-12.5) in CF infants. PAP concentrations were lower in premature infants 0.94 and 0.91 times for 25 to 31 + 6 weeks GA and 32 to 36 + 6 weeks respectively. A higher PAP concentration was observed in low-birth-weight infants (

There is an increasing interest in the potential of exhaled biomarkers, such as volatile organic compounds (VOCs), to improve accurate diagnoses and management decisions in pulmonary diseases. The objective of this manuscript is to systematically review the current knowledge on exhaled VOCs with respect to their potential clinical use in asthma, lung cancer, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and respiratory tract infections. A systematic literature search was performed in PubMed, EMBASE, Cochrane database, and reference lists of retrieved studies. Controlled, clinical, English-language studies exploring the diagnostic and monitoring value of VOCs in asthma, COPD, CF, lung cancer and respiratory tract infections were included. Data on study design, setting, participant characteristics, VOCs techniques, and outcome measures were extracted. Seventy-three studies were included, counting in total 3,952 patients and 2,973 healthy controls. The collection and analysis of exhaled VOCs is non-invasive and could be easily applied in the broad range of patients, including subjects with severe disease and children. Various research groups demonstrated that VOCs profiles could accurately distinguish patients with a pulmonary disease from healthy controls. Pulmonary diseases seem to be characterized by a disease specific breath-print, as distinct profiles were found in patients with dissimilar diseases. The heterogeneity of studies challenged the inter-laboratory comparability. In conclusion, profiles of VOCs are potentially able to accurately diagnose various pulmonary diseases. Despite these promising findings, multiple challenges such as further standardization and validation of the diverse techniques need to be mastered before VOCs can be applied into clinical practice.

Item does not contain fulltext Wheeze is a common symptom in preschool children. The role of bacteria, regulatory T (T(reg)) cells and their association with airway inflammation in preschool wheeze is largely unknown. We evaluated inflammatory markers in exhaled breath condensate (EBC), bacterial colonization and circulating T(reg) cells in preschool children with and without recurrent wheeze. We recruited 252 children (aged two to four years) with (N = 202) and without (N = 50) recurrent wheeze. EBC was collected using an efficient closed glass condenser. Inflammatory markers in EBC (Interleukin(IL)-2, IL-4, IL-8, IL-10, IL-13) were assessed using multiplex immunoassay. Nasal and throat swabs were analysed for presence of Streptococcus pneumoniae, Haemophilus (para)influenzae and Staphylococcus aureus. Proportions of T(reg) cells (CD4(+)CD25(high)CD127(-)) were quantified by flow cytometry. Recurrent wheezing children had elevated EBC levels of IL-2, IL-4, IL-10 and IL-13 compared to non-wheezers (odds ratio (95% confidence interval): 1.67 (1.23-2.27): 1.58 (1.15-2.18): 1.47 (1.14-1.90): 1.55 (1.16-2.06), p

Item does not contain fulltext BACKGROUND: Underdiagnosis and low levels of asthma control are frequent occurring problems in patients with asthma. OBJECTIVE: The study aim was to evaluate the ability of non-invasive inflammatory markers in exhaled breath to predict exacerbations of childhood asthma, and to assess the time course of changes in these exhaled markers before, during and after exacerbations. METHODS: The design was a prospective one-year longitudinal study. Regular two-month visits at the outpatient clinic were performed. Forty children with asthma (aged 6-16 years) participated. The primary outcome measure was the occurrence of an exacerbation. Assessment was made of the presence and severity of pulmonary symptoms, use of medication, and measurements of forced expiratory volume in 1 s using home monitor. The following independent parameters were assessed during outpatient visits: (1) exhaled nitric oxide, (2) inflammatory markers in exhaled breath condensate: acidity, nitrite, hydrogen peroxide, interleukin-1alpha, -5, -13, interferon-gamma, (3) lung function, (4) asthma control score. RESULTS: Thirty-eight of 40 children completed the study. Sixteen children developed exacerbations, of which ten were moderate and six severe. Univariate Cox regression analysis revealed that condensate acidity, interleukin-5 and asthma control score were significant predictors of an asthma exacerbation (P < 0.05). In the multivariate Cox regression analysis, exacerbations were best predicted by the asthma control score and by the level of interleukin-5 in exhaled breath condensate (Wald scores of 7.19 and 4.44, P = 0.007 and P = 0.035 respectively). The predicted survival curve of this multivariate model showed a two times reduced risk on exacerbations in the category of children with the 10% most optimal values of IL-5 and asthma control score. CONCLUSIONS AND CLINICAL RELEVANCE: Both exhaled breath condensate interleukin-5 level and asthma control score were significant predictors of asthma exacerbations. These findings open up the possibility of assessing the potential of such parameters to titrate asthma treatment in future studies.

Purpose: Most newborn screening (NBS) strategies for Cystic Fibrosis (CF) also identify carriers. However, it is unclear if parents want to be informed about their child's carrier status or not. Methods: Focus group discussions with pregnant couples to explore their opinions about disclosure of a carrier result for CF of their newborn. Results: All (n = 30) wanted to be informed when newborn screening would show their newborn being a CF-carrier. Their main reason was the implication of this knowledge for further family planning. Other family members could be informed and children within the family could be tested. Parents stated they have the right to know, but others also expressed that the choice of not being informed should be offered as well. Conclusion: Most parents want to be informed when NBS for CF reveals that their child is a CF-carrier, but the choice of not being informed should also be offered. © 2013 Elsevier Masson SAS.

Background. A reliable asthma diagnosis is challenging in preschool wheezing children. As inhaled corticosteroids (ICS) are more effective in asthmatics than in children with transient wheeze, an ICS response might be helpful in early asthma diagnosis.Methods. 175 children (aged two–four years) with recurrent wheeze received 200 μg Beclomethasone extra-fine daily for eight weeks. Changes in Exhaled Breath Condensate (EBC) biomarkers (pH, interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, IFN-γ, sICAM, and CCL-11), Fractional exhaled Nitric Oxide (FeNO), airway resistance, and symptoms were assessed. At six years of age a child was diagnosed as transient wheezer or asthmatic. Adjusted logistic regression analysis was performed with multiple testing correction.Results. 106 transient wheezers and 64 asthmatics were analysed at six years of age. Neither changes in EBC biomarkers, nor FeNO, airway resistance, or symptoms during ICS trial at preschool age were related to asthma diagnosis at six years of age. However, asthmatics had more airway symptoms before the start of the ICS trial than transient wheezers (P<0.01).Discussion. Although symptom score in preschool wheezing children at baseline was associated with asthma at six years of age, EBC biomarkers, airway resistance, or symptom response to ICS at preschool age could not predict asthma diagnosis at six years of age.