Publications by authors named "Edward Dompeling"

77 Publications

The risk of community-acquired pneumonia in children using gastric acid suppressants.

Eur Respir J 2021 Mar 18. Epub 2021 Mar 18.

Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical, Pharmacology, University of Utrecht, Utrecht, the Netherlands.

With the increased use of acid suppressants, significant potential complications, such as community-acquired pneumonia are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and community-acquired pneumonia. Our main objective was to evaluate the risk of community-acquired pneumonia in children using acid suppressants (proton pump inhibitors and/or histamine-2-receptor antagonists).We performed a cohort study using data from the Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to 4 unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of community-acquired pneumonia. The cohort consisted of 84 868 exposed and 325 329 unexposed children.Current use of proton pump inhibitors and histamine-2-receptor antagonists was associated with an increased risk of community acquired pneumonia, adjusted hazard ratio 2.05 (95% CI 1.90 to 2.22) and 1.80 (95% CI 1.67 to 1.94), respectively. The risk was even greater in patients with respiratory disease. Long term use >211 days of proton pump inhibitors and histamine-2-receptor antagonists led to a significantly greater risk of community-acquired pneumonia compared to short term use <31 days. After cessation of therapy, the risk remained increased for the following 7 months.The use of acid suppressants in children was associated with a doubled risk of community-acquired pneumonia. This risk increased with chronic use, respiratory disease and remained increased after discontinuation of therapy.
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http://dx.doi.org/10.1183/13993003.03229-2020DOI Listing
March 2021

Exhaled volatile organic compounds detect pulmonary exacerbations early in children with cystic fibrosis: results of a 1 year observational pilot study.

J Breath Res 2021 Feb 25;15(2):026012. Epub 2021 Feb 25.

Department of Paediatric Pulmonology, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

In patients with cystic fibrosis (CF), pulmonary exacerbations (PEx) have an important influence on well-being, quality of life, and lung function decline. Early detection combined with early treatment may prevent severe PEx. To determine whether early detection of PEx is possible by non-invasive markers (volatile organic compounds) in exhaled breath. In a 1 year prospective observational pilot study, 49 children with CF were studied. At clinical visits with an interval of 2 months, lung function, volatile organic compounds (VOCs) in exhaled breath by means of gas chromatography-time-of-flight-mass spectrometry, and medication use were assessed. PEx were recorded. Random forest (RF) classification modelling was used to select discriminatory VOCs, followed by building of receiver operating characteristic curves. An inverse relation between the predictive power of a set of VOCs and time between exhaled breath sampling and the onset of PEx was found. When this time period was within 7 d, the RF model with the nine most discriminatory VOCs was able to correctly predict 79% of the children with an upcoming PEx or remaining stable (sensitivity 79% and specificity 78%). This result was validated by means of bootstrapping within the RF classification model. PEx in children with CF can be detected at an early stage by means of exhaled VOCs. The highest predictive value was reached if time between sampling and the onset of an exacerbation was no longer than 7 d.
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http://dx.doi.org/10.1088/1752-7163/abda55DOI Listing
February 2021

Feasibility study on exhaled-breath analysis by untargeted Selected-Ion Flow-Tube Mass Spectrometry in children with cystic fibrosis, asthma, and healthy controls: Comparison of data pretreatment and classification techniques.

Talanta 2021 Apr 6;225:122080. Epub 2021 Jan 6.

Department of Analytical Chemistry, Applied Chemometrics and Molecular Modelling, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium. Electronic address:

Selected-Ion Flow-Tube Mass Spectrometry (SIFT-MS) has been applied in a clinical context as diagnostic tool for breath samples using target biomarkers. Exhaled breath sampling is non-invasive and therefore much more patient friendly compared to bronchoscopy, which is the golden standard for evaluating airway inflammation. In the actual pilot study, 55 exhaled breath samples of children with asthma, cystic-fibrosis and healthy individuals were included. Rather than focusing on the analysis of target biomarkers or on the identification of biomarkers, different data analysis strategies, including a variety of pretreatment, classification and discrimination techniques, are evaluated regarding their capacity to distinguish the three classes based on subtle differences in their full scan SIFT-MS spectra. Proper data-analysis strategies are required because these full scan spectra contain much external, i.e. unwanted, variation. Each SIFT-MS analysis generates three spectra resulting from ion-molecule reactions of analyte molecules with HO, NO and O. Models were built with Linear Discriminant Analysis, Quadratic Discriminant Analysis, Soft Independent Modelling by Class Analogy, Partial Least Squares - Discriminant Analysis, K-Nearest Neighbours, and Classification and Regression Trees. Perfect models, concerning overall sensitivity and specificity (100% for both) were found using Direct Orthogonal Signal Correction (DOSC) pretreatment. Given the uncertainty related to the classification models associated with DOSC pretreatments (i.e. good classification found also for random classes), other models are built applying other preprocessing approaches. A Partial Least Squares - Discriminant Analysis model with a combined pre-processing method considering single value imputation results in 100% sensitivity and specificity for calibration, but was less good predictive. Pareto scaling prior to Quadratic Discriminant Analysis resulted in 41/55 correctly classified samples for calibration and 34/55 for cross-validation. In future, the uncertainty with DOSC and the applicability of the promising preprocessing methods and models must be further studied applying a larger representative data set with a more extensive number of samples for each class. Nevertheless, this pilot study showed already some potential for the untargeted SIFT-MS application as a rapid pattern-recognition technique, useful in the diagnosis of clinical breath samples.
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http://dx.doi.org/10.1016/j.talanta.2021.122080DOI Listing
April 2021

Exhaled volatile organic compounds detect pulmonary exacerbations early in children with Cystic Fibrosis: results of a one-year observational pilot study.

J Breath Res 2021 Jan 11. Epub 2021 Jan 11.

Department of Toxicology, Maastricht University, Maastricht, Limburg, NETHERLANDS.

Background: In patients with Cystic fibrosis (CF), pulmonary exacerbations (PEx) have an important influence on well-being, quality of life, and lung function decline. Early detection combined with early treatment may prevent severe PEx.

Aim: To determine whether early detection of PEx is possible by non-invasive markers (volatile organic compounds) in exhaled breath.

Methods: In a one-year prospective observational pilot study, 49 children with CF were studied. At clinical visits with an interval of 2 months, lung function, volatile organic compounds (VOCs) in exhaled breath by means of gas chromatography-time-of-flight-mass spectrometry, and medication use were assessed. PEx were recorded. Random Forest (RF) classification modelling was used to select discriminatory VOCs, followed by building of Receiver Operating Characteristic curves.

Results: An inverse relation between the predictive power of a set of VOCs and time between exhaled breath sampling and the onset of PEx was found. When this time period was within 7 days, the RF model with the 9 most discriminatory VOCs was able to correctly predict 79% of the children with an upcoming PEx or remaining stable (sensitivity 79% and specificity 78%). This result was validated by means of bootstrapping within the RF classification model.

Conclusion: PEx in children with CF can be detected at an early stage by means of exhaled VOCs. The highest predictive value was reached if time between sampling and the onset of an exacerbation was no longer than 7 days.
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http://dx.doi.org/10.1088/1752-7163/abda55DOI Listing
January 2021

The Longitudinal Relationship Between Screen Time, Sleep and a Diagnosis of Attention-Deficit/Hyperactivity Disorder in Childhood.

J Atten Disord 2020 Sep 13:1087054720953897. Epub 2020 Sep 13.

Care and Public Health Research Institute (CAPHRI), Department of Epidemiology, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

Objective: To evaluate longitudinal associations between recreational screen time and sleep in early childhood, and attention-deficit/hyperactivity disorder (ADHD) at age 8 to 10 years.

Method: Questionnaires from 2,768 mother-child pairs from the Dutch KOALA Birth Cohort Study were used. General estimating equation logistic regression analyses examined associations between screen time and sleep at age 2, 4, and 6, and ADHD at age 8 to 10. Linear regression analysis examined associations between television time, sleep and CBCL/2-3 scores at age 2.

Results: Longitudinally, neither screen time nor sleep were associated with ADHD. Cross-sectionally, CBCL/2-3 externalizing symptom scores increased by 0.03 with every hour television time (95% CI 0.002-0.05) and increased by 0.02 per hour of less sleep (95% CI -0.03--0.01).

Conclusion: Despite an association with externalizing symptoms at age 2, screen time and sleep in early childhood were not associated with ADHD. Carefulness is warranted when extrapolating cross-sectional associations at early age to an ADHD diagnosis.
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http://dx.doi.org/10.1177/1087054720953897DOI Listing
September 2020

Discrepancy between Lung Function Measurements at Home and in the Hospital in Children with Asthma and CF.

J Clin Med 2020 May 26;9(6). Epub 2020 May 26.

Department of Paediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), 6202 AZ Maastricht, The Netherlands.

The Coronavirus pandemic stresses the importance of eHealth techniques to monitor patients at home. Home monitoring of lung function in asthma and cystic fibrosis (CF) may help to detect deterioration of lung function at an early stage, but the reliability is unclear. We investigated whether lung function measurements at home were comparable to measurements during clinical visits. We analysed prospectively collected data of two one-year observational cohort studies in 117 children (36 with CF and 81 with asthma). All patients performed forced expiratory volume in one second (FEV) measurements with a monitor at home. Paired FEV measurements were included if the measurement on the home monitor was performed on the same day as the FEV measurement on the pneumotachometer during a two monthly clinical visit. Bland-Altman plots and linear mixed model analysis were used. The mean difference (home measurement was subtracted from clinical measurement) in FEV was 0.18 L in CF (95% confidence interval (CI) 0.08-0.27 L; < 0.001) and 0.12 L in asthma (95%CI 0.05-0.19 L; < 0.001). FEV measurements at home were significantly lower than clinically obtained FEV measurements, which has implications for the application of this technique in the daily clinical situation.
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http://dx.doi.org/10.3390/jcm9061617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355967PMC
May 2020

Longitudinal Relationships between Asthma-Specific Quality of Life and Asthma Control in Children; The Influence of Chronic Rhinitis.

J Clin Med 2020 Feb 18;9(2). Epub 2020 Feb 18.

Department of Paediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), 6202 AZ Maastricht, The Netherlands.

Managing pediatric asthma includes optimizing both asthma control and asthma-specific quality of life (QoL). However, it is unclear to what extent asthma-specific QoL is related to asthma control or other clinical characteristics over time. The aims of this study were to assess in children longitudinally: (1) the association between asthma control and asthma-specific QoL and (2) the relationship between clinical characteristics and asthma-specific QoL. In a 12-month prospective study, asthma-specific QoL, asthma control, dynamic lung function indices, fractional exhaled nitric oxide, the occurrence of exacerbations, and the use of rescue medication were assessed every 2 months. Associations between the clinical characteristics and asthma-specific QoL were analyzed using linear mixed models. At baseline, the QoL symptom score was worse in children with asthma and concomitant chronic rhinitis compared to asthmatic children without chronic rhinitis. An improvement of asthma control was longitudinally associated with an increase in asthma-specific QoL (-value < 0.01). An increased use of β-agonists, the occurrence of wheezing episodes in the year before the study, the occurrence of an asthma exacerbation in the 2 months prior to a clinical visit, and a deterioration of lung function correlated significantly with a decrease in the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) total score (-values ≤ 0.01). Chronic rhinitis did not correlate with changes in the PAQLQ score over 1 year. The conclusion was that asthma control and asthma-specific QoL were longitudinally associated, but were not mutually interchangeable. The presence of chronic rhinitis at baseline did influence QoL symptom scores. β-agonist use and exacerbations before and during the study were inversely related to the asthma-specific QoL over time.
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http://dx.doi.org/10.3390/jcm9020555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074314PMC
February 2020

Gut microbiota in wheezing preschool children and the association with childhood asthma.

Allergy 2020 06 29;75(6):1473-1476. Epub 2020 Jan 29.

Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands.

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http://dx.doi.org/10.1111/all.14156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317729PMC
June 2020

Towards Prepared mums (TOP-mums) for a healthy start, a lifestyle intervention for women with overweight and a child wish: study protocol for a randomised controlled trial in the Netherlands.

BMJ Open 2019 11 19;9(11):e030236. Epub 2019 Nov 19.

Department of Paediatrics, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands

Introduction: Periconception obesity is associated with a higher risk for adverse perinatal outcomes such as gestational diabetes mellitus, preeclampsia, large for gestational age, operative delivery and preterm birth. Lifestyle interventions during pregnancy have resulted in insufficient effects on reducing these perinatal complications. A few reasons for this disappointing effect can be suggested: (1) the time period during pregnancy for improvement of developmental circumstances is too short; (2) the periconception period in which complications originate is not included; and (3) lifestyle interventions may not have been sufficiently multidisciplinary and customised. A preconception lifestyle intervention might be more effective to reduce perinatal complications. Therefore, the aim of the Towards Prepared mums study is to evaluate the effect of a lifestyle intervention starting prior to conception on lifestyle behaviour change.

Methods And Analysis: This protocol outlines a non-blinded, randomised controlled trial. One hundred and twelve women (18-40 years of age) with overweight or obesity (body mass index≥25.0 kg/m) who plan to conceive within 1 year will be randomised to either the intervention or care as usual group. The intervention group will receive a multidisciplinary, customised lifestyle intervention stimulating physical activity, a healthy diet and smoking cessation, if applicable. The lifestyle intervention and monitoring will take place until 12 months postpartum. The primary outcome is difference in weight in kg from baseline to 6 weeks postpartum. Secondary outcomes are gestational weight gain, postpartum weight retention, smoking cessation, dietary and physical activity habits. Furthermore, exploratory outcomes include body composition, cardiometabolic alterations, time to pregnancy, need for assisted reproductive technologies, perinatal complications of mother and child, and lung function of the child. Vaginal and oral swabs, samples of faeces, breast milk, placenta and cord blood will be stored for evaluation of microbial flora, epigenetic markers and breast milk composition. Furthermore, a cost-effectiveness analysis will take place.

Ethics And Dissemination: Ethical approval was obtained from the Medical Ethical Committee of Maastricht University Medical Centre+ (NL52452.068.15/METC152026). Knowledge derived from this study will be made available by publications in international peer-reviewed scientific journals and will be presented at (inter)national scientific conferences. A dissemination plan for regional and national implementation of the intervention is developed.

Trial Registration Number: ClinicalTrials.gov NCT02703753.
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http://dx.doi.org/10.1136/bmjopen-2019-030236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886927PMC
November 2019

Guideline use among different healthcare professionals in diagnosing attention deficit hyperactivity disorder in Dutch children; who cares?

BMC Psychol 2019 Jul 3;7(1):43. Epub 2019 Jul 3.

Department of Paediatrics, Maastricht University Medical Centre (MUMC+), PO Box 5800, 6202 AZ, Maastricht, The Netherlands.

Objective: Current data about Attention Deficit Hyperactivity Deficiency (ADHD) guideline use in the Netherlands are absent. This study analysed ADHD guideline use among different healthcare workers, and the use of key elements from these guidelines to diagnose ADHD.

Method: A survey assessing ADHD guideline use was distributed throughout the Netherlands to various health care professionals. Only professionals involved during the diagnostic process were included.

Results: Response rate among GPs was low (111/1450), but high among other health care professionals (251/287). A total of 362 surveys were analysed, 186 responders (51%) were involved during the diagnostic process. Overall guideline use was 64.5%; the national multidisciplinary guideline or a guideline made by a professional's own institution were most used. Psychiatrists, psychologists and paediatricians reported compliance with key elements of the guidelines such as gathering information from a third party (> 90%) and carrying out a developmental history (> 88%). Use of a standardized interview (< 52% often use) was low. Only paediatricians performed a physical examination regularly (88%).

Conclusion: Despite low general use of guidelines, psychiatrists, psychologists and paediatricians use similar key elements of ADHD guidelines. This study provides opportunities to improve care through increasing familiarity with ADHD guidelines and the use of standardized interviews.
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http://dx.doi.org/10.1186/s40359-019-0304-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610794PMC
July 2019

Exhaled Breath Condensate in Childhood Asthma: A Review and Current Perspective.

Front Pediatr 2019 25;7:150. Epub 2019 Apr 25.

Department of Pediatric Respiratory Medicine, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center, Maastricht, Netherlands.

Exhaled breath condensate (EBC) was introduced more than two decades ago as a novel, non-invasive tool to assess airway inflammation. This review summarizes the latest literature on the various markers in EBC to predict asthma in children. Despite many recommendations and two comprehensive Task Force reports, there is still large heterogeneity in published data. The biggest issue remains a lack of standardization regarding EBC collection, preservation, processing, and analysis. As a result, published studies show mixed or conflicting results, questioning the reproducibility of findings. A joint, multicenter research study is urgently needed to address the necessary methodological standardization.
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http://dx.doi.org/10.3389/fped.2019.00150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494934PMC
April 2019

Publisher Correction: Early detection of pulmonary exacerbations in children with Cystic Fibrosis by electronic home monitoring of symptoms and lung function.

Sci Rep 2018 Dec 13;8(1):17946. Epub 2018 Dec 13.

Department of Paediatric Respiratory Medicine, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-36407-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292896PMC
December 2018

Feasibility and diagnostic accuracy of an electronic nose in children with asthma and cystic fibrosis.

J Breath Res 2019 05 8;13(3):036009. Epub 2019 May 8.

Department of Paediatric Respiratory Medicine, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre+, Maastricht, The Netherlands.

The measurement of volatile organic compounds (VOCs) in exhaled breath is a promising tool for diagnosing and monitoring various lung diseases in children. Gas chromatography mass spectrometry (GC-MS) analysis is a frequently used standard technique for VOCs analysis. However, as GC-MS is an expensive and time-consuming technique, hand-held devices or electronic noses have been developed. Recently, the Aeonose was introduced as an easy-to-use hand-held eNose capable of point-of-care testing. Although first results using this eNose in adults are promising, studies in children are lacking. We therefore performed a cross-sectional study in 55 children and adolescents ≥6 years of age (20 children with moderate to severe asthma, 13 children with CF, and 22 healthy controls). The feasibility of the Aeonose was high (>98% successful measurements). The diagnostic accuracy was high for discriminating asthma from CF (Area Under the Receiver Operating Characteristic Curve [AUC] 0.90 [95% Confidence Interval 0.78-1.00] sensitivity 89% [65%-98%], specificity 77% [46%-94%]), and for the distinction between CF and healthy controls (AUC 0.87 [0.74-1.00], sensitivity 85% [54%-97%], specificity 77% [54%-91%]). However, the diagnostic accuracy for the discrimination between asthma and healthy controls was modest (AUC 0.79 [0.63-0.94], sensitivity 74% [49%-90%], specificity 91% [69%-98%]). This is the first study to report test results of the Aeonose in children and adolescents ≥6 years. This eNose showed a high feasibility with modest to good diagnostic accuracies in asthma and CF. This study was registered at clinicaltrial.gov (NCT03377686).
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http://dx.doi.org/10.1088/1752-7163/aae158DOI Listing
May 2019

Risk factors for lung disease progression in children with cystic fibrosis.

Eur Respir J 2018 06 7;51(6). Epub 2018 Jun 7.

Dept of Paediatric Respiratory Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

To identify potential risk factors for lung disease progression in children with cystic fibrosis (CF), we studied the longitudinal data of all children with CF (aged ≥5 years) registered in the Dutch CF Registry (2009-2014).Lung disease progression was expressed as a decline in lung function (forced expiratory volume in 1 s (FEV) % pred) and pulmonary exacerbation rate. Potential risk factors at baseline included sex, age, best FEV % pred, best forced vital capacity % pred, genotype, body mass index z-score, pancreatic insufficiency, medication use (proton pump inhibitors (PPIs), prophylactic antibiotics and inhaled corticosteroids), CF-related diabetes, allergic bronchopulmonary aspergillosis and colonisation with The data of 545 children were analysed. PPI use was associated with both annual decline of FEV % pred (p=0.017) and future pulmonary exacerbation rate (p=0.006). Moreover, lower FEV % pred at baseline (p=0.007), prophylactic inhaled antibiotic use (p=0.006) and pulmonary exacerbations in the baseline year (p=0.002) were related to pulmonary exacerbations in subsequent years.In a cohort of Dutch children with CF followed for 5 years, we were able to identify several risk factors for future exacerbations. In particular, the association between PPI use and lung disease progression definitely requires further investigation.
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http://dx.doi.org/10.1183/13993003.02509-2017DOI Listing
June 2018

Children With ADHD Symptoms: Who Can Do Without Specialized Mental Health Care?

J Atten Disord 2020 01 22;24(1):104-112. Epub 2018 Feb 22.

Maastricht University Medical Centre, The Netherlands.

A new Dutch Child and Youth Act should reduce specialized mental health care for children with symptoms of ADHD. Characteristics of children referred to a specialized ADHD clinic are explored to give direction to this intention. Data of 261 children who underwent a multidisciplinary best practice evaluation (including rating scales, and demographic, psychological, and somatic findings) were analyzed. Univariable and multivariable logistic regression models were used to find predictive variables for the need of specialized mental health care. Collected data were heterogeneous. (Sub)clinical total scores on the Teacher Report Form (TRF) and Child Behavior Checklist (CBCL) were predictive variables for specialized mental health care. Also children with divorced parents were more often referred to specialized care. (Sub)clinical scores on the CBCL and TRF increased the need for specialized care, but comprehensive assessment of every child with ADHD symptoms was necessary to differentiate between levels of care.
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http://dx.doi.org/10.1177/1087054718756194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935830PMC
January 2020

Recruiting families for an intervention study to prevent second-hand smoke exposure in children.

BMC Pediatr 2018 01 31;18(1):19. Epub 2018 Jan 31.

Department of Paediatric Respiratory Medicine, Maastricht University Medical Centre (MUMC+) / CAPHRI School for Public Health and Primary Care, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.

Background: We evaluated the effectiveness of different recruitment strategies used in a study aimed at eliminating/reducing second-hand smoke (SHS) exposure in Dutch children 0-13 years of age with a high risk of asthma.

Methods: The different strategies include: 1) questionnaires distributed via home addresses, physicians or schools of the children; 2) cohorts from other paediatric studies; 3) physicians working in the paediatric field (family physicians, paediatricians and Youth Health Care (YHC) physicians); and 4) advertisements in a local newsletter, at child-care facilities, and day-care centres.

Results: More than 42,782 families were approached to take part in the screening of which 3663 could be assessed for eligibility. Of these responders, 196 families met the inclusion criteria for the study. However, only 58 (one third) could be randomised in the trial, mainly because of no interest or time of the parents. The results showed that recruiting families who expose their children to SHS exposure is very challenging, which may be explained by lack of 'recognition' or awareness that SHS occurs in homes. The presence of asthma in the family, respiratory symptoms in the children, and even incentives did not increase parental motivation for participation in the study.

Conclusions: The recruitment process for an intervention program addressing SHS exposure in children was considerably more challenging and time consuming than anticipated. Barriers at both a parents level and a doctor's level can be discriminated.
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http://dx.doi.org/10.1186/s12887-018-0983-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793411PMC
January 2018

Motivational interviewing and urine cotinine feedback to stop passive smoke exposure in children predisposed to asthma: a randomised controlled trial.

Sci Rep 2017 11 13;7(1):15473. Epub 2017 Nov 13.

Department of Paediatric Pulmonology, Maastricht University Medical Center (MUMC+)/CAPHRI School for Public Health and Primary Care, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

We tested the effectiveness of a program consisting of motivational interviewing (MI) and feedback of urine cotinine to stop passive smoking (PS) in children at risk for asthma. Fifty-eight families with children 0-13 years with a high risk of asthma and PS exposure were randomised in a one-year follow-up study. The intervention group received the intervention program during 6 sessions (1/month) and the control group received measurements (questionnaires, urine cotinine, and lung function) only. The primary outcome measure was the percentage of families stopping PS (parental report verified and unverified with the child's urine cotinine concentration <10 μg/l) in children during the intervention program. The analyses were performed with Mixed Logistic Regression. After 6 months, a significant group difference was observed for the unverified parental report of stopping PS in children: 27% of parents in the intervention group versus 7% in the control group. For the verified parental report, the difference was similar (23% versus 7%) but was not statistically significant. Despite a limited sample size, the results suggest that the intervention program is probably an effective strategy to stop PS in children. A program longer than 6 months might be necessary for a longer lasting intervention effect.
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http://dx.doi.org/10.1038/s41598-017-15158-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684321PMC
November 2017

Early detection of pulmonary exacerbations in children with Cystic Fibrosis by electronic home monitoring of symptoms and lung function.

Sci Rep 2017 09 27;7(1):12350. Epub 2017 Sep 27.

Department of Paediatric Respiratory Medicine, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

Pulmonary exacerbations (PEx) in Cystic Fibrosis (CF) are associated with an increased morbidity and even mortality. We investigated whether early detection of PEx in children with CF is possible by electronic home monitoring of symptoms and lung function. During this one-year prospective multi-centre study, 49 children with CF were asked to use a home monitor three times a week. Measurements consisted of a respiratory symptom questionnaire and assessment of Forced Expiratory Volume in one second (FEV1). Linear mixed-effects and multiple logistic regression analyses were used. In the 2 weeks before a PEx, the Respiratory Symptom Score (RSS) of the home monitor increased (p = 0.051). The FEV1 as percentage of predicted (FEV1%pred) did not deteriorate in the 4 weeks before a PEx. Nevertheless, the FEV1%pred at the start of exacerbation was significantly lower than the FEV1%pred in the non-exacerbation group (mean difference 16.3%, p = 0.012). The combination of FEV1%pred and RSS had a sensitivity to predict an exacerbation of 92.9% (CI 75.0-98.8%) and a specificity of 88.9% (CI 50.7-99.4%). The combination of home monitor FEV1%pred and RSS can be helpful to predict a PEx in children with CF at an early stage.
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http://dx.doi.org/10.1038/s41598-017-10945-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617859PMC
September 2017

Factors associated with changes in health-related quality of life in children with cystic fibrosis during 1-year follow-up.

Eur J Pediatr 2017 Aug 9;176(8):1047-1054. Epub 2017 Jun 9.

Department of Paediatric Respiratory Medicine, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre + (MUMC+), Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00431-017-2928-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511302PMC
August 2017

A European Respiratory Society technical standard: exhaled biomarkers in lung disease.

Eur Respir J 2017 04 26;49(4). Epub 2017 Apr 26.

Philips Research, High Tech Campus 11, Eindhoven, The Netherlands.

Breath tests cover the fraction of nitric oxide in expired gas (), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for , official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and , new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.
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http://dx.doi.org/10.1183/13993003.00965-2016DOI Listing
April 2017

Can exhaled volatile organic compounds predict asthma exacerbations in children?

J Breath Res 2017 03 1;11(1):016016. Epub 2017 Mar 1.

Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

Background: Asthma control does not yet meet the goals of asthma management guidelines. Non-invasive monitoring of airway inflammation may help to improve the level of asthma control in children.

Objectives: (1) To identify a set of exhaled volatile organic compounds (VOCs) that is most predictive for an asthma exacerbation in children. (2) To elucidate the chemical identity of predictive biomarkers.

Methods: In a one-year prospective observational study, 96 asthmatic children participated . During clinical visits at 2 month intervals, asthma control, fractional exhaled nitric oxide, lung function (FEV, FEV/VC) and VOCs in exhaled breath were determined by means of gas chromatography time-of-flight mass spectrometry. Random Forrest classification modeling was used to select predictive VOCs, followed by plotting of receiver operating characteristic-curves (ROC-curves).

Results: An inverse relationship was found between the predictive power of a set of VOCs and the time between sampling of exhaled breath and the onset of exacerbation. 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 unidentified VOC.

Conclusion: VOCs in exhaled breath showed potential for predicting asthma exacerbations in children within 14 days after sampling. Before using this in clinical practice, the validity of predicting asthma exacerbations should be studied in a larger cohort.
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http://dx.doi.org/10.1088/1752-7163/aa5a8bDOI Listing
March 2017

Associations between asthma, overweight and physical activity in children: a cross-sectional study.

BMC Public Health 2016 09 1;16:919. Epub 2016 Sep 1.

Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.

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.
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http://dx.doi.org/10.1186/s12889-016-3600-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009538PMC
September 2016

A Multifactorial Weight Reduction Programme for Children with Overweight and Asthma: A Randomized Controlled Trial.

PLoS One 2016 13;11(6):e0157158. Epub 2016 Jun 13.

Department of Paediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC), Maastricht, the Netherlands.

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 (p<0.01) in the intervention group and -0.12±0.34 points (p<0.01) in the control group. This change over time did not differ between groups (p>0.05). 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 (p<0.001), which was significantly greater than the 6.1 ± 8.4% in the control group (p<0.05).

Conclusions & 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157158PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905647PMC
July 2017

Biomarkers in Exhaled Breath Condensate Are Not Predictive for Pulmonary Exacerbations in Children with Cystic Fibrosis: Results of a One-Year Observational Study.

PLoS One 2016 6;11(4):e0152156. Epub 2016 Apr 6.

Department of Pediatric Pulmonology, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

Background: Cystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations. These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis.

Aim: To investigate the diagnostic accuracy of a set of inflammatory markers in EBC to predict pulmonary exacerbations in children with CF.

Methods: In this one-year prospective observational study, 49 children with CF were included. During study visits with an interval of 2 months, a symptom questionnaire was completed, EBC was collected, and lung function measurements were performed. The acidity of EBC was measured directly after collection. Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), and macrophage migration inhibitory factor (MIF) were measured using high sensitivity bead based flow immunoassays. Pulmonary exacerbations were recorded during the study and were defined in two ways. The predictive power of inflammatory markers and the other covariates was assessed using conditionally specified models and a receiver operating characteristic curve (SAS version 9.2). In addition, k-nearest neighbors (KNN) algorithm was applied (SAS version 9.2).

Results: Sixty-five percent of the children had one or more exacerbations during the study. The conditionally specified models showed an overall correct prediction rate of 55%. The area under the curve (AUC) was equal to 0.62. The results obtained with the KNN algorithm were very similar.

Conclusion: Although there is some evidence indicating that the predictors outperform random guessing, the general diagnostic accuracy of EBC acidity and the EBC inflammatory markers IL-6, IL-8, TNF-α and MIF is low. At present it is not possible to predict pulmonary exacerbations in children with CF with the chosen biomarkers and the method of EBC analysis. The biochemical measurements of EBC markers should be improved and other techniques should be considered.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152156PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822839PMC
August 2016

Evidence for a Cystic Fibrosis Enteropathy.

PLoS One 2015 20;10(10):e0138062. Epub 2015 Oct 20.

Department of Paediatric Gastroenterology & Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University Medical Centre, Maastricht, the Netherlands.

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<0.001), and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05). Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05). No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use.

Conclusion: This study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138062PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617711PMC
June 2016

LucKi Birth Cohort Study: rationale and design.

BMC Public Health 2015 Sep 21;15:934. Epub 2015 Sep 21.

Department of Health Services Research, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands.

Background: Infancy and childhood are characterized by rapid growth and development, which largely determine health status and well-being across the lifespan. Identification of modifiable risk factors and prognostic factors in critical periods of life will contribute to the development of effective prevention and intervention strategies. The LucKi Birth Cohort Study was designed and started in 2006 to follow children from birth into adulthood on a wide range of determinants, disorders, and diseases. During preschool and school years, the primary focus is on the etiology and prognosis of atopic diseases (eczema, asthma, and hay fever) and overweight/obesity.

Methods/design: LucKi is an ongoing, dynamic, prospective birth cohort study, embedded in the Child and Youth Health Care (CYHC) practice of the 'Westelijke Mijnstreek' (a region in the southeast of the Netherlands). Recruitment (1-2 weeks after birth) and follow-up (until 19 years) coincide with routine CYHC contact moments, during which the child's physical and psychosocial development is closely monitored, and anthropometrics are measured repeatedly in a standardised way. Information gathered through CYHC is complemented with repeated parental questionnaires, and information from existing registries of pharmacy, hospital and/or general practice. Since the start already more than 5,000 children were included in LucKi shortly after birth, reaching an average participation rate of ~65 %.

Discussion: The LucKi Birth Cohort Study provides a framework in which children are followed from birth into adulthood. Embedding LucKi in CYHC simplifies implementation, leads to low maintenance costs and high participation rates, and facilitates direct implementation of study results into CYHC practice. Furthermore, LucKi provides opportunities to initiate new (experimental) studies and/or to establish biobanking in (part of) the cohort, and contributes relevant information on determinants and health outcomes to policy and decision makers. Cohort details can be found on www.birthcohorts.net .
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http://dx.doi.org/10.1186/s12889-015-2255-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578419PMC
September 2015

Prediction of asthma exacerbations in children by innovative exhaled inflammatory markers: results of a longitudinal study.

PLoS One 2015 23;10(3):e0119434. Epub 2015 Mar 23.

Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+),Maastricht, The Netherlands.

Background: In asthma management guidelines the primary goal of treatment is asthma control. To date, asthma control, guided by symptoms and lung function, is not optimal in many children and adults. Direct monitoring of airway inflammation in exhaled breath may improve asthma control and reduce the number of exacerbations.

Aim: 1) To study the use of fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC), in the prediction of asthma exacerbations in a pediatric population. 2) To study the predictive power of these exhaled inflammatory markers combined with clinical parameters.

Methods: 96 asthmatic children were included in this one-year prospective observational study, with clinical visits every 2 months. Between visits, daily symptom scores and lung function were recorded using a home monitor. During clinical visits, asthma control and FeNO were assessed. Furthermore, lung function measurements were performed and EBC was collected. Statistical analysis was performed using a test dataset and validation dataset for 1) conditionally specified models, receiver operating characteristic-curves (ROC-curves); 2) k-nearest neighbors algorithm.

Results: Three conditionally specified predictive models were constructed. Model 1 included inflammatory markers in EBC alone, model 2 included FeNO plus clinical characteristics and the ACQ score, and model 3 included all the predictors used in model 1 and 2. The area under the ROC-curves was estimated as 47%, 54% and 59% for models 1, 2 and 3 respectively. The k-nearest neighbors predictive algorithm, using the information of all the variables in model 3, produced correct predictions for 52% of the exacerbations in the validation dataset.

Conclusion: The predictive power of FeNO and inflammatory markers in EBC for prediction of an asthma exacerbation was low, even when combined with clinical characteristics and symptoms. Qualitative improvement of the chemical analysis of EBC may lead to a better non-invasive prediction of asthma exacerbations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119434PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370663PMC
March 2016

An ADAM33 polymorphism associates with progression of preschool wheeze into childhood asthma: a prospective case-control study with replication in a birth cohort study.

PLoS One 2015 13;10(3):e0119349. Epub 2015 Mar 13.

Department of Paediatric Respiratory Medicine, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands.

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<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis).

Results: In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze.

Conclusion: Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119349PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358930PMC
February 2016