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Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity? Study Design and Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry. Results: Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV 1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels. Interpretation: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.

Background: Atopic dermatitis (AD) affects children of all skin types. Most research has focused on light skin types. Studies investigating biomarkers in people with AD with dark skin types are lacking. Objectives: To explore skin barrier and immune response biomarkers in stratum corneum (SC) tape strips from children with AD with different skin types. Methods: Tape strips were collected from lesional and nonlesional forearm skin of 53 children with AD and 50 controls. We analysed 28 immunomodulatory mediators, and natural moisturizing factors (NMF) and corneocyte morphology. Results: Interleukin (IL)-1β, IL-18, C-X-C motif chemokine (CXCL) 8 (CXCL8), C-C motif chemokine ligand (CCL) 22 (CCL22), CCL17, CXCL10 and CCL2 were significantly higher (P

Background Asthma prevalence is 339 million globally. ‘Severe asthma’ (SA) comprises subjects with uncontrolled asthma despite proper management. Objectives To compare asthma from diverse ethnicities and environments. Methods A cross-sectional analysis of two adult cohorts, a Brazilian (ProAR) and a European (U-BIOPRED). U-BIOPRED comprised of 311 non-smoking with Severe Asthma (SAn), 110 smokers or ex-smokers with SA (SAs) and 88 mild to moderate asthmatics (MMA) while ProAR included 544 SA and 452 MMA. Although these projects were independent, there were similarities in objectives and methodology, with ProAR adopting operating procedures of U-BIOPRED. Results Among SA subjects, age, weight, proportion of former smokers and FEV1 pre-bronchodilator were similar. The proportion of SA with a positive skin prick tests (SPT) to aeroallergens, the scores of sino-nasal symptoms and quality of life were comparable. In addition, blood eosinophil counts (EOS) and the % of subjects with EOS > 300 cells/μl were not different. The Europeans with SA however, were more severe with a greater proportion of continuous oral corticosteroids (OCS), worse symptoms and more frequent exacerbations. FEV1/FVC pre- and post-bronchodilator were lower among the Europeans. The MMA cohorts were less comparable in control and treatment, but similar in the proportion of allergic rhinitis, gastroesophageal reflux disease and EOS >3%. Conclusions ProAR and U-BIOPRED cohorts, with varying severity, ethnicity and environment have similarities, which provide the basis for global external validation of asthma phenotypes. This should stimulate collaboration between asthma consortia with the aim of understanding SA, which will lead to better management.

OBJECTIVES: To determine whether imaging findings can be used to differentiate between impact and non-impact head trauma in a group of fatal and non-fatal abusive head trauma (AHT) victims. METHODS: We included all AHT cases in the Netherlands in the period 2005-2012 for which a forensic report was written for a court of law, and for which imaging was available for reassessment. Neuroradiological and musculoskeletal findings were scored by an experienced paediatric radiologist. RESULTS: We identified 124 AHT cases; data for 104 cases (84%) were available for radiological reassessment. The AHT victims with a skull fracture had fewer hypoxic ischaemic injuries than AHT victims without a skull fracture (p=0.03), but the relative difference was small (33% vs. 57%). There were no significant differences in neuroradiological and musculoskeletal findings between impact and non-impact head trauma cases if the distinction between impact and non-impact head trauma was based on visible head injuries, as determined by clinical examination, as well as on the presence of skull fractures. CONCLUSIONS: Neuroradiological and skeletal findings cannot discriminate between impact and non-impact head trauma in abusive head trauma victims. Language: en

Rhinovirus (RV) is a frequent pathogen in young children, eliciting symptoms ranging from common colds to wheezing illnesses and lower respiratory tract infections. The recently identified RV-C seems to be associated with asthma exacerbations and more severe disease, but results vary. We studied the prevalence and severity of infection with RV in an unselected birth cohort. Children with respiratory symptoms entered the symptomatic arm of the cohort and were compared with asymptomatic children. Severity of wheezing and other respiratory symptoms was registered. Respiratory viruses were evaluated using throat and nasopharyngeal swabs on first presentation and after recovery (wheezing children). RV genotyping was performed on RV-PCR positive samples. RV was the most prevalent respiratory virus and was found in 58/140 symptomatic children (41%), 24/96 (25%) control children and 19/74 (26%) wheezing symptomatic children after recovery (p

Aim. To establish the validity and applicability of a revised version of the QUality Of care Through the patient's Eyes-Chronic Non Specific Lung Disease (QUOTE-CNSLD) instrument in a population of children with controlled and partly controlled asthma. Methods. Randomized controlled trial evaluating quality of care in three follow-up settings: follow-up by the general practitioner, the pediatrician, and the specialized asthma nurse, for a period of 2 years. Results. One hundred and seven children were recruited, 45 from general practice and 62 from hospital practice. The revised QUOTE-CNSLD instrument completed by parents at baseline (T0), after 1 year (T1) and after 2 years (T2) showed that a process-, a structure-, and an asthma-specific domain could be deduced (Cronbach's alpha of 0.81, 0.82, and 0.62). A separate five-item "child-specific" questionnaire about their caregiver, completed by children, has a Cronbach's alpha of 0.88. The revised instrument could discriminate between quality of care in different follow-up settings for children with stable asthma, and the asthma-specific domain showed particularly discriminative properties. Quality aspects with potential for improvement could be derived from the scores in all three study groups. Conclusion. The revised QUOTE-CNSLD instrument is applicable in a pediatric population with stable asthma and it has discriminative value between different follow-up settings

Rationale Exercise-induced bronchoconstriction (EIB) is defined as a transient narrowing of the airways induced by exercise. Repetitive measurements of spirometric parameters, such as FEV1 and expiratory flows, and forced oscillation technique (FOT) measurements can be used to analyze the dynamics of EIB. A single high dose of fluticasone propionate (FP) protects against EIB. The aim of the study was to analyze the effect of FP on the dynamics of exercise-induced airway narrowing as measured with FOT and spirometry. Methods Twelve children performed an exercise challenge on 2 separate days, 4 hr after inhalation of 1 mg FP (pressurized metered dose inhaler) or a placebo. Before and after the exercise flow-volume loops as well as the FOT (frequency range: 4–32 Hz) were measured. Results The FEV1, and FEF50 fell significantly after exercise within groups; the peak fall in FEV1 after FP was significantly smaller than after placebo (respectively, 19.3 ± 14.6% and 29.2 ± 14.8%, P = 0.03, 95% CI: 0.9–18.8%). The fall in FEV1 and FEF50 peaked 3 min after exercise and showed a subsequent partial recovery. The fall in the FEV1/FVC ratio showed a later peak fall (12 min after exercise). The resistance increased while the reactance decreased significantly after exercise. FP significantly decreased the maximal increase in Rrs6 when compared to the placebo (respectively 176.5 ± 59.1% and 201.0 ± 63.8%, P = 0.05, 95% CI: 0.5–48.7%). The maximal decrease in Xrs6 was not significantly affected by FP (P = 0.06). Conclusion Repetitive spirometric and FOT measurements after exercise show a rapid narrowing and steady recovery of the patency of the conducting airways, and indicate a delayed and prolonged recovery of the smaller airways. A single high dose of inhaled FP seems to employ its effect mainly in the conducting airways. Pediatr. Pulmonol. 2011; 46:849–856. © 2011 Wiley-Liss, Inc.

To cite this article: van der Aa LB, van Aalderen WMC, Heymans HSA, Henk Sillevis Smitt J, Nauta AJ, Knippels LMJ, Ben Amor K, Sprikkelman AB, the Synbad Study Group. Synbiotics prevent asthma-like symptoms in infants with atopic dermatitis. Allergy 2011; 66: 170–177. Abstract Background: Infants with atopic dermatitis (AD) have a high risk of developing asthma. We investigated the effect of early intervention with synbiotics, a combination of probiotics and prebiotics, on the prevalence of asthma-like symptoms in infants with AD. Methods: In a double-blind, placebo-controlled multicentre trial, ninety infants with AD, age

– De mate van astmacontrole staat centraal bij de monitoring van astma bij kinderen. – Voor het meten van astmacontrole lijken de Asthma Control Test (ACT) en de Asthma Control Questionnaire (ACQ) geschikte instrumenten. Of hierdoor ook werkelijk klinische verbetering wordt bereikt is niet bekend. – Aanbevolen wordt ten minste eenmaal per jaar spirometrie met reversibiliteitsmeting te verrichten. In de monitoring van astma is geen plaats voor routine bronchoprovocatietests. – Het meten van stikstofmonoxide in uitademingslucht geeft een indruk van de mate van eosinofiele luchtwegontsteking. Toepassing van deze test bij astmamonitoring bij kinderen (aanpassen van inhalatiesteroiden) leidde in recent onderzoek niet tot betere astmacontrole.

As part of a longitudinal cohort study, now in its second decade, we determined PCDDs/Fs dl-PCBs and PBDEs in serum of adolescents with known perinatal PCDD/F exposure. Of the original cohort, 33 adolescents aged 14-19 years, who had been studied previously during their neonatal (n=60), toddler and pre-pubertal period (n=41) agreed to participate in the current follow-up. PCDD/F-, dl-PCB- and PBDE congeners were measured using GC/MS. Current serum levels of PCDD/Fs determined in our cohort were relatively low (mean of 2.2 pg/g) compared to the perinatal exposure. No correlation between perinatal exposure and current serum PCDD/F was found. Planar PCB TEQ levels were 2.2 pg/g. Current summation operatorPBDE levels were 8.7 ng/g lipid. There was one outlier with a summation operatorPBDE of 74 ng/g lipid. The presence of this high value indicates that the exposure pathway is different from PCDD/F and PCB, most likely by dust and food contaminated with dust. Concluding we can say that current PCDD/F levels are quite low compared to the perinatal PCDD/F exposure of the cohort. PBDE levels however are relatively high compared to other European countries, more research on possible health effects of these levels, especially for subjects with outlier concentrations, should be performed.

BackgroundIn 2008, the European Respiratory Society Task Force proposed the terms multiple-trigger wheeze (MTW) and episodic (viral) wheeze (EVW) for children with wheezing episodes. We determined MTW and EVW prevalence, their 24-month stability and predictiveness for asthma. MethodsIn total, 565 preschoolers (1-, 2- and 3-year-olds) in primary care with respiratory symptoms were followed until the age of 6years when asthma was diagnosed. MTW status and EVW status were determined using questionnaire data collected at baseline and after one and 2years. We distinguished 3 phenotypes and determined their 24-month stability, also accounting for treatment with inhaled corticosteroids (ICS). Logistic regression was used to analyse the phenotypes' associations with asthma. ResultsTwo hundred and eighty-one children had complete information. MTW and EVW were stable in 10 of 281 (3.6%) and 24 of 281 (8.5%), respectively. The odds of developing asthma for children with stable MTW and stable EVW were 14.4 (1.7-119) and 3.6 (1.2-11.3) times greater than those for children free of wheeze (for at least 1year). ICS was associated with increased stability of MTW and EVW. ConclusionsStable multiple-trigger and stable episodic viral wheeze are relatively uncommon. However, 1- to 3-year-olds with stable MTW are at much increased risk of asthma.

To identify factors associated with asthma control in a multi-ethnic paediatric population. We interviewed 278 children with paediatrician diagnosed asthma (aged 7-17 years) and one of their parents. Asthma control was assessed with the Asthma Control Questionnaire (ACQ). Detailed information about sociodemographic variables, asthma medication, knowledge of asthma, inhalation technique and environmental factors were collected. Turkish and Moroccan parents were interviewed in their language of choice. Logistic regression analyses were used to identify correlates of asthma control. Of the 278 children, 85 (30.6%) were Dutch, 84 (30.2%) were Moroccan, 58 (20.9%) were Turkish and 51 (18.3%) were Surinamese. Overall, almost 60% had a status of well-controlled asthma, as indicated by the ACQ. Only 51 of the 142 (35.9%) Moroccan and Turkish parents had a good comprehension of the Dutch language. In logistic regression analyses the risk of having uncontrolled asthma was significantly higher among Surinamese children (OR 2.3; 95% CI 1.06-4.83), respondents with insufficient comprehension of the Dutch language (OR 2.3; 95% CI 1.08-4.78), children using woollen blankets (OR 9.8; 95% CI 1.52-63.42), and significantly lower among male (OR 0.5; 95% CI 0.31-0.91) and non-daily users of inhaled corticosteroids (OR 0.6; 95% CI 0.38-1.07). In conclusion, ethnicity as well as insufficient comprehension of the Dutch language appeared to be independent risk factors for uncontrolled asthma. Special attention should be given to children from immigrants groups for example by calling in an interpreter by physicians when comprehension is insufficient. © 2006 Elsevier Ltd. All rights reserved.

The aim of this study was to validate the QUOTAC, a questionnaire on day and night time respiratory symptoms in asthmatic children. Validity was examined by measuring agreement between the QUOTAC and a self-report diary in children aged 6 to 16 years, divided in an asthma group and a control group. As an extra interest in our study a sum score was computed as a measure of the severity of asthma. This study shows that the QUOTAC is discriminative between asthmatic and healthy children and is a reliable and sensitive scale for measuring the severity of asthma. However, cut-off scores for mild, moderate, or severe asthma should be investigated in further research.

Background Sinonasal pathology in adults with Cystic Fibrosis (CF) is common but the extent of CT-abnormalities and symptoms of sinonasal disease in children with CF and the age of onset are less frequently studied. Methods In this observational, cross-sectional study 58 children with CF from two CF centres were included. All subjects completed a questionnaire regarding sinonasal symptoms, underwent a CT scan of the paranasal sinuses, and in each subject a culture of the upper airways was performed. Subjects were divided in 6 age cohorts (0–2, 3–5, 6–8, 9–11, 12–14 and 15–17years) and were divided into severe and mild CF based on their CFTR mutation. Opacification of the sinonasal system of the subjects was compared with opacification on MRI-scans of an age-matched control group without CF. Results Most frequently reported symptoms were nasal obstruction and posterior/anterior nasal discharge. Opacification was abundant in every age cohort of the study group and was significantly more compared to the control group. In patients with severe CF the opacification was higher than subjects with mild CF. Upper airway cultures showed predominantly Staphylococcus aureus , Haemophilus influenzae and Pseudomonas aeruginosa. Conclusion CT-abnormalities indicating sinonasal disease and symptoms are present from shortly after birth which may argue for a thorough examination of the upper airways in children with CF.

Asthma patients have been reported to be sensitive to breathlessness, independent of the degree of airway obstruction. Paying attention and task performance may induce changes in breathing pattern and these in turn may mediate such a feeling. The present experiment investigates whether strained breathing induced by an arithmetic task was different in children with asthma compared to healthy children.Methods: Seven healthy and eight asthmatic but symptom-free school children were equipped with electrodes for surface electromyographic (EMG) measurements of diaphragm, abdominal and intercostal (IC) muscles and with a strain gauge to monitor the pattern of breathing at rest and during an arithmetic task. The relative duration of exhalation and the relative speed of exhalation are used as measures of straining. The phase angle of maximal. respiratory muscle activities relative to the maximal. chest extension (MCE) are additional discriminating parameters.Results: Asthmatic children breathed more slowly and already at rest the phase of their respiratory muscle activity appears to be different. While in healthy children the maximal activity of the (left)abdominal muscles occurred 5 +/- 29% later than the MCE, in children with asthma the maximal. activity occurred 26 +/- 30% of the cycle earlier than MCE. In children with asthma the activity of the IC muscles starts weaning already at 10 +/- 30% before MCE, in contrast to the healthy children in which intercostal muscle weaning starts only at 1 +/- 24% after MCE. During arithmetic, the significant difference between the groups in this respect disappeared.Conclusion: Children with asthma show, even at rest, signs of respiratory muscle straining, probably in order to keep close control over the airflow in a similar way as healthy children during mental tasks. Such a 'careful' breathing pattern may work to prevent airway irritation also when they are free of symptoms. (c) 2005 Published by Elsevier Ltd.

Alfa-1-antitrypsinedeficientie is een autosomaal recessieve aandoening. De prevalentie is het hoogst bij de blanke Noord-Europese populatie. Het klinische beeld is zeer variabel en kan uiteenlopen van milde transaminasestijging in de eerste levensjaren tot levercirrose. Tevens kan het zich op de volwassen leeftijd presenteren met longemfyseem. De leverschade wordt veroorzaakt door een vouwfout van het gemuteerde α1-antitrypsine met leverstapeling als gevolg. Het longemfyseem wordt veroorzaakt door deficientie van α1-antitrypsine door het ontbreken van de protease-inhibitoractiviteit van α1-antitrypsine met longdestructie als gevolg. Wij bespreken de genetische aspecten, de pathofysiologie, het klinische beeld, de diagnostiek, de behandelingsmogelijkheden en de voor- en nadelen van screening van α1-antitrypsinedeficientie.

Background: A study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus (RSV-LRTI). Methods: In a multicentre randomised controlled trial patients were randomised to receive either intravenous dexamethasone (0.15 mg/kg 6 hourly for 48 hours) or placebo. End points were the duration of mechanical ventilation, length of stay (LOS) in the pediatric intensive care unit (PICU) and in hospital, and the duration of supplemental oxygen administration. Results: Thirty seven patients received dexamethasone and 45 received placebo. There was no significant difference in any of the end points between the two groups. In a post hoc analysis patients were stratified into those with mild gas exchange anomalies ( PaO2/FiO(2) > 200 mm Hg and/or mean airway pressure 10 cm H2O, pneumonia group). In the 39 patients with bronchiolitis the duration of mechanical ventilation was 4.3 days shorter in the dexamethasone group than in the placebo group (4.9 v 9.2 days, 95% CI - 7.8 to - 0.8, p= 0.02) and the duration of supplemental oxygen was 3.6 days shorter (7.7 v 11.3 days, 95% CI - 8.0 to - 0.1, p= 0.048). No differences in end points were found in the pneumonia group. Conclusions: Dexamethasone had no beneficial effect in patients mechanically ventilated for RSV-LRTI but was found to have a beneficial effect in patients with bronchiolitis

Low endogenous cortisol levels appear to contribute to the pathophysiology of nocturnal asthma. Lower cortisol levels are associated with lower forced expiratory volume in one second (FEV1) levels in children with asthma. The aim of the present study was to identify whether substitution of low serum cortisol with intravenous hydrocortisone decreases 24-h FEV1 variation and/or indirect measures of airway inflammation. Hydrocortisone was given over 24 h in a double-blind randomised crossover design to 26 subjects. FEV1 was measured every 4 h during 24 h; blood eosinophils and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured at 04:00 h and 16:00 h. Cortisol levels increased during the night and morning hours. FEV1 values were higher at all time points in children with nocturnal asthma (n=10; 24-h FEV1 variation greater than or equal to15%) which was significant at 08:00 h, unlike in the non-nocturnal asthma (NA-) group (n=16). Numbers of eosinophils; (10(9.)L(-1)) at 04:00 h decreased in the asthma group (median 0.61 (range 0.05-1.42) versus 0.52 (0.05-1.79)). Provocative dose causing a 20% fall in FEV1 (PD20) metbacholine did not change, whereas PD20 AMP improved only at 16:00 h in the NA- group (72.0 (0.13-144.0) versus 144.0 (2.25-144.0) mg(.)mL(-1)). These results show that substitution of lower endogenous 24-h values of. cortisol contribute to higher forced expiratory volume in one second values and a decrease of blood eosinophils as an inflammatory marker in more severe airway obstruction

Astma is een van de meest voorkomende chronische ziekten op de kinderleeftijd. Wereldwijd is de prevalentie bij kinderen in de leeftijd van 6-7 jaar 11-12% en bij kinderen van 13-14 jaar 13-14%. Hoewel er de laatste decennia van de vorige eeuw in de westerse wereld een toename in de prevalentie van astma en andere allergische aandoeningen werd gezien, lijkt deze de laatste jaren te stabiliseren of zelfs af te nemen. In Nederland was de prevalentie bij kinderen van 8-9 jaar 13,4% in 1981 en 9,1% in 2001. Een duidelijke oorzaak voor deze afname is er niet, maar het blijft nog steeds de meest voorkomende chronische ziekte bij kinderen. Kinderen van Turkse en Marokkaanse oorsprong lijken minder vaak astma te hebben dan kinderen van Nederlandse, Surinaamse en Antilliaanse herkomst.

BACKGROUND: During the baseline period of a clinical trial comparing different dosage schedules of inhaled steroids, asthmatic children (aged 6-10 years) were expected to meet the inclusion criterion of airways hyper-responsiveness (PD(20) methacholine < 80 micro g) after withdrawal of inhaled corticosteroids for 2-8 weeks. However, many children failed to do so. OBJECTIVE: It has been shown that young wheezing children may outgrow their symptoms. We investigated if differences between children with and without airways hyper-responsiveness after withdrawal of inhaled corticosteroids were compatible with differences between transient and persistent wheezers found in other studies. METHODS: Seventy-eight children entered the study, of which 41 developed airways hyper- responsiveness after withdrawal of inhaled corticosteroids, and 37 did not. These two groups of children were compared with respect to differences in demographic, clinical, and immunological features (IL-4, IL-5, IL-10, and IFN-gamma produced by Con A stimulated peripheral mononuclear cells (PBMCs) and serum IL-4, IL-5 and soluble intercellular adhesion molecule-1 (sICAM-1)). RESULTS: Hyper-responsive children had more atopic features (positive RAST, high IgE, eczema), lower levels of FEV1 and lower concentrations of sICAM-1 than non-hyper-responsive children. Apart from a borderline significantly higher IL-4 production in the hyper-responsive group, other immunologic parameters were comparable. Multivariate logistic regression analysis showed that high serum IgE, low FEV1, and low sICAM-1 levels were independently associated with the presence of airways hyper-responsiveness after stopping inhaled corticosteroids. Atopy was associated with higher concentrations of IL-4 in the hyper-responsive group. CONCLUSION: After withdrawal of inhaled corticosteroids many children previously diagnosed with asthma did not develop airways hyper-responsiveness. We conclude that hyper-responsive children share features with persistent wheezers as found in previous studies, whereas the non-hyper- responsive children may represent transient wheezers.

Polychlorinated biphenyls (PCBs) and dioxins (PCDDs/Fs) are well-known endocrine disrupters. This paper strives to elucidate the data on reproductive consequences of perinatal dioxin and PCB exposure in men and women. We focused on the following end-points: sex-ratio, endometriosis, menstrual cycle characteristics, sperm quality, and prematurity. We summarize 46 papers and compare their results including effects seen after exposure to background concentrations. Seven of twelve studies showed a decrease in sex-ratio after parental dioxin or PCB exposure. In three of the seven studies, effects were seen after paternal exposure and in three after maternal exposure. In eight of the nine studies on menstrual cycle characteristics, abnormalities were associated with PCB or dioxin exposure, however the results differed. In three studies PCB and TCDD were associated with longer menstrual cycles, while three studies indicated that an increase in PCB/PCDF exposure was associated with shorter cycles. Five studies showed effects on menstrual bleeding with higher PCB or dioxin exposure. A higher rate of irregular menstrual cycles in exposed women was seen in four studies. The conflicting outcomes probably result from variability in study design, timing of exposure and endocrine disrupting properties of the measured congeners. Nine of sixteen studies detected higher PCB or dioxin exposure in women with endometriosis. However, the manner of diagnosing endometriosis and the character of the studies varied from prospective to retrospective. Five of eight studies focusing on sperm quality showed that men, with higher serum concentrations of PCBs and/or PCB congeners and/or PCDFs, had reduced sperm quality, including increased abnormal morphology and reduced motility. The exposure timeframe seemed important here. There are two studies addressing preterm birth in relation to PCBs, one mentioned a shortening of three days of gestational age, two other studies did not find a relation. Recently one study related a shorter gestational age of half a week with overall dioxin activity measured with the CALUX method in cord blood, particularly in boys. In conclusion, exposure to PCBs and dioxins has a negative effect on the reproductive systems of human populations. Although some speculations have been made, the exact mechanism of these effects and the interactions of these compounds with other endocrine disruptors are not yet known. Age at exposure and congener specific properties are probably crucial in interpreting the observed results.

The feasibility of moderately severe airway hyperresponsiveness (AH) was examined as an inclusion criterion for clinical trials in asthmatic children.During the baseline period of a long-term clinical trial in asthmatic children, maintenance therapy with fluticasone (200 µg·day−1) was stopped for a maximum of 8 weeks and methacholine challenges were performed at 2-week intervals or earlier if the patients' condition deteriorated. Patients were eligible to continue the study if the provocative dose of methacholine causing a 20% fall in forced expired volume in one second (FEV1) (PD20) was Fifty-one per cent of the children did not develop a PD2020201and mean maximal expiratory flow than patients with a PD20≥80 µg. Forty-four per cent of the patients with a PD20≥80 µg did not have any symptoms during the wash-out period and 39% of these patients remained free from symptoms during one year follow-up.The results of this study suggest that recruiting asthmatic children for clinical trials may be difficult if airways hyperresponsiveness is used as the sole inclusion criterion.

Despite differences in study design, follow-up studies consistently show that approximately half of the infants with respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) go on to have recurrent wheezing episodes during childhood. Respiratory symptoms are associated with abnormal lung function, including bronchial hyper-responsiveness. Wheezing symptoms following RSV LRTI gradually decrease, and it appears that during school age airway morbidity is no longer related to RSV LRTI during infancy. Mechanisms underlying the association between RSV LRTI and long-term airway morbidity are poorly understood. On the one hand, abnormal airway function that is congenitally present or acquired before RSV LRTI occurs could be the cause of both RSV LRTI and subsequent recurrent wheezing. On the other hand, it is possible that RSV LRTI causes changes in the lower airways or the immune system that result in long-term airway morbidity. Animal models suggest that RSV infection can promote the development of allergic sensitization, but most studies in humans do not indicate a role for atopy in the development of recurrent wheezing following RSV LRTI.

The single-breath maneuver used to measure nitric oxide (NO) in adults cannot be performed by young children. We, therefore, developed a method of measuring NO in mixed exhaled gas collected during tidal breathing. NO was measured in mixed exhaled gas during 5 min of tidal breathing in 113 children 4-14 years of age: 22 nonasthmatics, 21 asthmatic children not taking inhaled corticosteroids, and 70 asthmatic children using inhaled corticosteroids. Exhaled NO levels (median, range) were significantly lower in nonasthmatic controls (median, range: 7, 2-10 ppb) than in asthmatic children on inhaled corticosteroids (8, 3-25 ppb; 95% CI for difference in medians with those of controls, 0-4 ppb), and in those not on inhaled corticosteroids (13, 6-37, ppb; 95% CI for difference in medians, 5-17 ppb). Asthmatic children not using inhaled corticosteroids had significantly higher exhaled NO levels than asthmatic children using inhaled corticosteroids (95% CI for difference in medians, 3-10 ppb). The tidal breathing method is a useful and practical way of measuring exhaled NO levels in children regardless of their age.

Abnormale reacties op koemelk komen op de zuigelingen- en vroege kinderleeftijd regelmatig voor en worden aangeduid als koemelkallergie of koemelkintolerantie. De incidentie van koemelkallergie varieert van 2 tot 5%. De diagnose koemelkallergie dient te worden gesteld op de klinische reactie op koemelk bij de zogenaamde eliminatie-provocatietest. De prognose van koemelkallergie voor wat betreft het later kunnen verdragen van koemelkeiwit, is goed. Op 3-jarige leeftijd kan ongeveer 90% van de kinderen die als zuigeling koemelkallergie hadden, koemelkeiwit verdragen. Daarentegen is de prognose voor wat betreft de latere ontwikkeling van andere allergische aandoeningen slechts in enkele prospectieve langetermijnstudies onderzocht. De resultaten van deze vervolgonderzoeken laten zien, dat de kans op ontwikkeling van astma, atopische dermatitis, allergische rinitis en conjunctivitis, en voedselintolerantie voor andere voedingsmiddelen dan koemelk later op de kinderleeftijd aanzienlijk is. Aangezien er geen placebogecontroleerd onderzoek kan worden uitgevoerd, is het vooralsnog niet mogelijk om een harde uitspraak te doen over een secundair preventief effect van voedingsinterventie op de latere ontwikkeling van allergische aandoeningen. Uit recent onderzoek kan de conclusie worden getrokken dat koemelkallergie op de zuigelingenleeftijd moet worden beschouwd als de eerste uiting van een allergische aanleg en niet als een zelfstandige risicofactor voor het later ontstaan van andere allergische aandoeningen.

Verschillende factoren worden verondersteld een rol te spelen bij het ontstaan van allergie. Een onderverdeling is te maken in genetische factoren en pre- en postnatale omgevingsfactoren. Voorbeelden van prenatale omgevingsfactoren zijn roken door de moeder en dieet. Voorbeelden van postnatale risicofactoren zijn geboortemaand, infecties, darmflora, gezinsgrootte, inhalatieallergenen, (passief) roken en luchtvervuiling. Interventieonderzoek moet in de komende jaren laten zien hoe groot de invloed is van deze factoren. Strategieen voor de preventie van allergie moeten gericht zijn op alle factoren die betrokken zijn bij het ontstaan van allergie.

Follow-up studies have demonstrated that bronchiolitis caused by respiratory syncytial virus (RSV) is strongly associated with wheezing in the ensuing years. During the acute infection the immune response may induce long-lasting detrimental effects, thereby contributing to post-bronchiolitis wheezing (PBW). Therefore, immune-modulating drugs like corticosteroids, administered in the acute phase of RSV bronchiolitis, may prevent PBW and asthma. To evaluate this, we performed a controlled prospective follow-up study after a randomized double-blind placebo-controlled intervention in the acute phase with oral prednisolone. Fifty-four patients under 2 years of age and hospitalized for RSV bronchiolitis between 1992 and 1995 were randomly assigned to prednisolone 1 mg/kg/day for 7 days or placebo. At the mean age of 5 years, 47 patients had completed their follow-up. Patients were divided into four groups: no wheezing, transient wheezing (wheezing during the first year of life); persistent wheezing (wheezing during the first year of life and asthma at the age of 5); and late-onset wheezing (no wheezing during the first year of life but asthma at the age of 5). Prevalence of wheezing and asthma were investigated through an interview by telephone, using a standardized questionnaire. We found no significant differences between the prednisolone- and the placebo-treated group in the number of patients with transient wheezing (8% vs. 17%), persistent wheezing (42% vs. 31%), or late-onset wheezing (17% vs. 13%). We conclude that oral prednisolone during the acute phase of RSV bronchiolitis is not effective in preventing PBW or asthma at the mean age of 5 years. Pediatr Pulmonol. 2000; 30: 92-96.

We have recently found that changes in lung sounds correspond well with a 20% fall in the forced expiratory volume in 1 s (FEV1) after methacholine challenge in asthmatic children. Up to now, little was known about the agreement between a 20% fall in FEV1 and a change in lung sounds after repeated bronchial challenge. In this study we investigated the agreement between the total cumulative histamine dose causing a fall in FEV1 of 20% or more (PD20) and the detection of a change in lung sounds (PDlung sounds) after two bronchial challenges on different occasions in asthmatic children. Fifteen asthmatic children (nine boys), mean age 10.8 years (range 9-15), were studied. All performed two histamine challenge tests on 2 days, with a 24 h to 1 week interval. Lung sounds were recorded over the trachea for 1 min and stored on tape. Lung sounds were analysed directly and also scored from the tape-recording by a blinded second investigator. Wheeze, cough, and an increase in respiratory rate were assessed. The relationship between PD20 and PDlung sounds was calculated by Bland and Altman's measurement of agreement. Eleven children had a positive challenge test (PD20 less than or equal to 16.0 mg ml(-1)) on both test days; four had a positive challenge on one test day. In 24 out of 26 positive challenges, wheeze, cough, prolonged expiration and/or increased respiratory rate were detected one dose-step before, or at the dose-step of histamine that induced a fall in FEV1 of 20% or more. In two challenges, PD20 was not detected by a change in lung sounds. In four out of four negative challenges (PD20 less than or equal to 16.0 mg ml(-1)) no change in lung sounds could be detected. Good agreement between the logarithm of PD20 and the logarithm of PDlung sounds was found on both test days. The mean difference was 0.04 and the limits of agreement (d +/- 2 SD of the differences) were 0.04 +/- 0.41. A good agreement was found between the total cumulative histamine dose causing a fall in FEV1 of 20% or more and the detection of a change in lung sounds after two bronchial challenges on different occasions in asthmatic children.

Background: Pancreatic enzyme replacement therapy frequently fails to correct intestinal fat malabsorption completely in cystic fibrosis (CF) patients. The reason for this failure is unknown. Objective: We investigated whether fat malabsorption in CF patients treated with pancreatic enzymes is caused by insufficient lipolysis of triacylglycerols or by defective intestinal uptake of long-chain fatty acids. Design: Lipolysis was determined on the basis of breath (CO2)-C-13 recovery in 10 CF patients receiving pancreatic enzyme replacement therapy after they ingested 1,3-distearoyl,2[1-C-13]octanoyl glycerol ([C-13]MTG). Intestinal uptake of long-chain fatty acids was determined by analyzing plasma [C-13]linoleic acid ([C-13]LA) concentrations after patients ingested [C-13]LA. For 3 d, dietary intakes were recorded and feces were collected. Results: Fecal fat excretion ranged from 5.1 to 27.8 g/d ((x) over bar +/- SD: 11.1 +/- 7.0 g/d) and fat absorption ranged from 79% to 93% (89 +/- 5%). There was no relation between breath (CO2)-C-13 recovery and dietary fat absorption (r = 0.04) after ingestion of [C-13]MTG. In contrast, there was a strong relation between 8-h plasma [C-13]LA concentrations and dietary fat absorption (r = 0.88, P

Over the last two decades much has been written about the consequences of perinatal dioxin and PCB exposure in humans. In this paper we strive to elucidate the data on puberty in relation to these endocrine disruptive compounds in human populations. Effects in PCB/dioxin-exposed human populations on puberty are seen, not only in highly exposed cohorts, but also in average populations with background exposures. Study showed effects like increased weight, a delay in pubic hair growth and male genital development in boys, sex-hormone homeostasis, reduced penile length, and delayed age at first ejaculation after PCB exposure. Effects seen after dioxin exposure include retarded initiation and stage of breast development in girls, earlier menarche, disruption of sex hormone homeostasis, reduced testicular volume and reduced penile length in boys. The data published by different studies were inconclusive as a result of different methodological setup as well as because of multiple exposure settings. Populations were exposed to different mixtures of dioxin/PCB congeners or mixtures with other endocrine disrupters, and therefore synergistic and antagonistic effects with PCBs and dioxins are possible. Dioxinlike compounds disturb the hormonal balance mainly through interaction with the Ah receptor, which may influence the synthesis of hormones or their transport proteins. However, we have to keep in mind that hormonal balance during puberty could also be altered by disruption of the thyroid homeostasis. Another important possible mechanism is the induction of epigenetic changes or effects on genetic polymorphism. The fact that exposure to background concentrations of dioxin-like compounds and PCBs also has effects on the reproductive development is disconcerting and warrants further research and long term follow-up studies.

The median age of survival in patients with cystic fibrosis (CF) has improved considerably. Despite this improvement, deterioration of pulmonary function and decrease in exercise capacity are still the main problems for many patients. Although dyspnoea is a common complaint in CF patients, relatively little regard has been paid to this symptom. This study examined the relationship between dyspnoea, bicycle exercise capacity and pulmonary function in patients with CF. In 14 patients in a stable clinical condition, pulmonary function [forced expiratory volume in 1 s (FEV1), inspiratory vital capacity (IVC)], bicycle exercise capacity [maximum exercise capacity (Wmax)], subjective degree of dyspnoea during daily living [Medical Research Council (MRC) dyspnoea scale], and during exercise (Borg scale) were assessed. The mean (SD) age of the patients was 25 (6.8) years, FEV1 was 41 (19)% predicted, IVC was 63 (17)% predicted and FEV1/IVC ratio was 47 (10)%; median (range) Wmax was 55 (0-79)% predicted. Bicycle exercise test performance appeared to be mainly determined by pulmonary function and MRC dyspnoea grade; multiple regression equation containing FEV1 and dyspnoea accounted for 76% of the variance in Wmax (% predicted) (Wmax = -7.9 dysp + 1.1 FEV1, +24). Exercise dyspnoea, assessed by the Borg scale, showed a significant linear correlation with minute ventilation. (VE), maximal voluntary ventilation (MVV) (%) (r = 0.76; P < 0.001). Medical Research Council dyspnoea score correlated relatively poorly with FEV1 (% predicted) (r = -0.17; n.s.) and IVC (% predicted) (r = -0.48; n.s.). Borg score at maximal exercise did not correlate with MRC dyspnoea score (r = -0.07). Borg50% score correlated significantly with MRC dyspnoea score (r = 0.61; P < 0.05). These results show that dyspnoea has an influence on exercise capacity. Dyspnoea score showed a large inter-individual variation, not strongly related to pulmonary function. It is concluded that dyspnoea deserves more attention in CF patients and needs to be assessed in rehabilitation programmes and other intervention studies in these patients.

The majority of patients with cystic fibrosis (CF) will grow into adulthood. Despite this improvement in survival, the disease is progressive, especially with respect to the decline in pulmonary function, which in turn may have an impact on a patient's quality of life. In this study we evaluated the quality of life in CF adults and examined the relationship between quality of life and pulmonary function, exercise capacity, and dyspnea. We assessed in 15 patients in stable clinical condition their forced expired volume in the first second (FEV1) inspiratory vital capacity (IVC), cycle exercise capacity (Wmax), and subjective degrees of dyspnea during daily living (MRC dyspnea scale). Quality of life was assessed with the Sickness Impact Profile (SIP). A sample of 100 healthy individuals, ranging in age from 18 to 30 years, served as the control group. Mean (SD) age of the patients was 25.9 (7.3) years, FEV1 was 38 (16)% predicted, IVC was 65 (17)% predicted, FEV1 IVC ratio was 46 (10)%, and Wmax was 90 (54) W. The overall SIP and physical SIP scores in CF patients were significantly higher than in the controls, indicating more impairment in overall and physical functioning in the patients than in the control group (P < 0.001). The psychosocial SIP score did not differ significantly between the two groups. Overall SIP score correlated poorly with FEV1 % predicted (r = -0.33; n.s) and IVC % predicted (r = -0.36; n.s.) but showed a better and significant relationship to the maximal exercise capacity (r = -0.57; P < 0.05). MRC dyspnea scores showed a strong correlation with overall SIP scores (r = 0.75; P < 0.001). These results show that CF affects quality of life in adults primarily due to a limitation in physical functioning. Psychosocial functioning did not differ from that of healthy controls. Exercise capacity and dyspnea scores were related to the impairment in the quality of life. Therefore, the effects of programs aimed to improve exercise capacity and reduce dyspnea on CF patients' quality of life need to be evaluated.

BACKGROUND: Experimental and clinical evidence suggests that respiratory syncytial virus (RSV) bronchiolitis is an immune mediated disease. Corticosteroids might therefore be effective in the treatment of RSV bronchiolitis. METHODS: A randomised double blind trial was conducted in children up to two years of age admitted to hospital with RSV bronchiolitis to compare prednisolone (1 mg/ kg/day orally for seven days) with placebo. Variables used for the efficacy analysis were a daily symptom score and the length of time in hospital in the non- ventilated patients, and the duration of mechanical ventilation and the length of time in hospital in the ventilated patients. RESULTS: Fifty four patients were included in the trial, 40 of whom were non- ventilated (20 in each group) and 14 were ventilated (seven in each group). During the first three days of treatment the symptom score decreased significantly faster in the prednisolone group than in the placebo group (mean (SE) decrease -1.2 (0.2) points/day versus -0.6 (0.2) points/day; mean (95% confidence interval (CI)) for difference = - 0.6 (-0.1 to -1.2); p = 0.02). The mean duration of hospital stay of all 40 non-ventilated patients was not significantly different between the two groups. In the ventilated patients the duration of mechanical ventilation was not significantly different, but the length of time in hospital was six days shorter in the prednisolone group than in the placebo group (mean (SE) 11.0 (0.7) versus 17.0 (2.0) days; mean (95% CI) difference = 7.0 (1.8 to 10.2) days; p < 0.01). CONCLUSIONS: These results suggest that prednisolone may be effective in accelerating the clinical recovery of children admitted to hospital with RSV bronchiolitis.

The aim of the study was to investigate whether seasonal differences in house dust mite (HDM) allergen exposure influence the circadian peak expiratory flow (PEF) amplitude in asthmatic children. Asthmatic children (n = 25) with a solitary allergy to HDM were studied in spring and in autumn. All used inhaled corticosteroids (ICS) regularly. Six days after withdrawal of ICS, PEF amplitude (every 4 h during 24 h, highest-lowest/percentage of mean value) was assessed. HDM allergen (HDMA) in living rooms, bedrooms, and mattresses was collected. HDMA levels were not always highest in autumn. PEF amplitudes in spring and autumn did not correlate with HDMA levels in the same season. However, the seasonal difference in PEF amplitude (autumn value - spring value) correlated positively and significantly with the seasonal difference in HDMA exposure levels from the mattresses (rho = 0.34, p

The influence of exogenous factors in the home on the circadian variation of airway obstruction has not been fully assessed in children with asthma. The aim of the present study was to investigate the contribution of exogenous stimuli to the degree of peak expiratory flow (PEF) variability during 24 h. Fifty-five children (33 boys and 22 girls; mean age, 9.3 +/- 1.7 yr) with symptoms of asthma, increased bronchial responsiveness, and a solitary allergy to house dust mite (HDM) participated. Their asthma symptoms were well-controlled for at least 4 mo with daily inhaled corticosteroids (ICS) and beta 2-adrenergic drugs if needed. Symptoms, peripheral blood eosinophils, total IgE, and specific IgE to HDM were assessed. Spirometry and PC20 histamine were performed. PEF amplitudes during 24 h (highest minus lowest as a percentage of the day's mean value) were obtained at home during and 6 d after withdrawal of ICS. Dust samples were collected from the total area of the living rooms, bedrooms, mattresses (n = 25), and classrooms to obtain the HDM allergen (HDMA) exposure to Der p I and Der p II. Family smoking habits, presence of pets, and types of floor-covering were recorded on a checklist. Mean PEF amplitude did not increase after withdrawal of ICS, but absolute PEF values were significantly lower (p = 0.05) at midnight and 4:00 A.M. Twenty-six children (47%) were exposed to environmental tobacco smoke (ETS), and 23 (42%) kept pets. Mattresses contained significantly higher amounts of HDMA compared with other locations. PEF amplitude after withdrawal of ICS was significantly higher in children exposed to ETS, a pet, or a high HDMA level in their mattress than in children who were not exposed (ETS: 29.7% [3.9 to 56.6] versus 19.4% [0.0 to 56.6], p

Bij een kind dat acuut benauwd is, moet men zich snel een indruk vormen van de ernst van de benauwdheid, de mate van progressie en de dreiging van respiratoire insufficientie. Een (bijna) totale luchtwegafsluiting kenmerkt zich doordat het kind niet kan praten of hoesten en heftige ademhalingsbewegingen maakt of kokhalst.

Item does not contain fulltext Inhaled medication is the cornerstone of the pharmacological treatment of patients with asthma and COPD. The major two classes of inhaled medication include corticosteroids (ICS) and bronchodilators. There is a wide diversity in molecules in both classes. Moreover, there is a wide variation in delivery systems. The correct use of inhalers is not granted and patients often incur in many mistakes when using pMDIs and DPIs, despite repeated instructions. A better matching between patient and device could be accomplished if the physician is aware of: (1) the patient characteristics (disease, severity, fluctuation in airflow obstruction, etc); (2) what class of medication is indicated; (3) where in the lung the medication should be delivered; and, (4) how this can be best achieved by a given device in this specific patient. We focus on the prescription of pMDIs and DPIs at the GP office or at the outpatient clinic of the hospital, and we propose an evidence based approach enabling the caregiver to make a rational choice in only a few minutes by just considering the following four simple questions: Who?, What? Where? and How? (the so-called 3W-H approach).

The present study was set up to investigate whether salmeterol in children with asthma already treated with inhaled corticosteroids (ICS) leads to a sustained bronchodilator effect and decreased bronchial responsiveness, both during the day and night. Furthermore, we investigated whether cessation of salmeterol leads to a rebound increase in bronchial responsiveness. Forty children with asthma (aged 7-15 yrs) using ICS participated in a randomized, double-blind, parallel study. They received either twice daily 50 micrograms salmeterol or placebo. FEV1 and provocative concentration of methacholine that caused a 20% fall in FEV1 (PC20) were measured at 4:00 P.M. and 4:00 A.M. at baseline and after 16 wk. The same measurements were performed at 4:00 P.M. at 8 h after the first dose, and after 1 and 8 wk. After cessation of the study drug, FEV1 and PC20 were measured at 12 and 20 h and after 1 wk. Overall mean FEV1 from 1 to 16 wk of treatment was significantly higher in the salmeterol group than in the placebo group (difference, 4.9 +/- 2.0%, p = 0.01). Evolution in time of FEV1 did not differ significantly between the two groups (p = 0.09). Overall mean PC20 from 1 to 16 wk of treatment was not significantly higher with salmeterol than with placebo (difference, 0.7 +/- 0.4 doubling dose [DD] p = 0.07); evolution in time of PC20 did not differ significantly between the two groups (p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)

Since nocturnal symptoms indicate more severe asthma, we investigated their frequency in a hospital-based population of asthmatic children. Recognition of these symptoms offers the possibility to introduce appropriate treatment. We studied 796 consecutive children with asthma (mean (SD) age 9 (4) yrs) attending a hospital clinic, to determine whether these nocturnal symptoms predicted that daytime activities would be affected, and also the patients' perception of disease severity. At the end of a regular out-patient clinic visit, the answers to seven different questions concerning nocturnal symptoms in the previous 3 weeks were recorded. The forced expiratory volume in one second (FEV(1)) was greater than or equal to 90% predicted in 98% of the population that was able to perform lung function measurements (72% of the total population). In 38% of the patients with nocturnal symptoms, these symptoms were reported spontaneously. When asked for, nocturnal symptoms were reported by 47% of the children; 6% every night and 34% at least once a week. Cough was the most frequently reported symptom (31%). Children with nocturnal symptoms had a lower FEV(1), scored their perception of asthma as more severe, and had their daytime activities affected more than those without nocturnal symptoms. Doctors should specifically ask about nocturnal symptoms, as not all patients with nocturnal symptoms report them spontaneously and they predict more severe disease.

Intravenous antibiotics and enteral tube feeding at home for the treatment of pulmonary exacerbations and underweight condition in cystic fibrosis (CF) patients have become tools that are used in many cystic fibrosis centres. The experience with home care programmes from different countries is quite conclusive. If the necessary preparations are made, such as training of staff and patients, and financial support is arranged, home care is easy to put into practice. Optimal patient compliance is also necessary. Home care is as effective as hospital treatment for selected patients, and less expensive. Experience has increased during many treatment periods in different cystic fibrosis centres, and only a few adverse events have been recorded, indicating that home care is safe. However, the most important gain for cystic fibrosis patients is the reduction of hospital admission time, which means a definite improvement in the quality of life.

The objective of this study was to assess the cost-effectiveness of the use of prebiotics for the primary prevention of atopic dermatitis in The Netherlands. A model was constructed using decision analytical techniques. The model was developed to estimate the health economic impact of prebiotic preventive disease management of atopic dermatitis. Data sources used include published literature, clinical trials and official price/tariff lists and national population statistics. The comparator was no supplementation with prebiotics. The primary perspective for conducting the economic evaluation was based on the situation in The Netherlands in 2009. The results show that the use of prebiotics infant formula (IMMUNOFORTISA (R)) leads to an additional cost of a,not sign 51 and an increase in Quality Adjusted Life Years (QALY) of 0.108, when compared with no prebiotics. Consequently, the use of infant formula with a specific mixture of prebiotics results in an incremental cost-effectiveness ratio (ICER) of a,not signA 472. The sensitivity analyses show that the ICER remains in all analyses far below the threshold of a,not sign 20,000/QALY. This study shows that the favourable health benefit of the use of a specific mixture of prebiotics results in positive short- and long-term health economic benefits. In addition, this study demonstrates that the use of infant formula with a specific mixture of prebiotics is a highly cost-effective way of preventing atopic dermatitis in The Netherlands