The ADEM2 project: early pathogenic mechanisms of preschool wheeze and a randomised controlled trial assessing the gain in health and cost-effectiveness by application of the breath test for the diagnosis of asthma in wheezing preschool children.

BACKGROUND: The prevalence of asthma-like symptoms in preschool children is high. Despite numerous efforts, there still is no clinically available diagnostic tool to discriminate asthmatic children from children with transient wheeze at preschool age. This leads to potential overtreatment of children outgrowing their symptoms, and to potential undertreatment of children who turn out to have asthma. Our research group developed a breath test (using GC-tof-MS for VOC-analysis in exhaled breath) that is able to predict a diagnosis of asthma at preschool age. The ADEM2 study assesses the improvement in health gain and costs of care with the application of this breath test in wheezing preschool children. METHODS: This study is a combination of a multi-centre, parallel group, two arm, randomised controlled trial and a multi-centre longitudinal observational cohort study. The preschool children randomised into the treatment arm of the RCT receive a probability diagnosis (and corresponding treatment recommendations) of either asthma or transient wheeze based on the exhaled breath test. Children in the usual care arm do not receive a probability diagnosis. Participants are longitudinally followed up until the age of 6 years. The primary outcome is disease control after 1 and 2 years of follow-up. Participants of the RCT, together with a group of healthy preschool children, also contribute to the parallel observational cohort study developed to assess the validity of alternative VOC-sensing techniques and to explore numerous other potential discriminating biological parameters (such as allergic sensitisation, immunological markers, epigenetics, transcriptomics, microbiomics) and the subsequent identification of underlying disease pathways and relation to the discriminative VOCs in exhaled breath. DISCUSSION: The potential societal and clinical impact of the diagnostic tool for wheezing preschool children is substantial. By means of the breath test, it will become possible to deliver customized and high qualitative care to the large group of vulnerable preschool children with asthma-like symptoms. By applying a multi-omics approach to an extensive set of biological parameters we aim to explore (new) pathogenic mechanisms in the early development of asthma, creating potentially interesting targets for the development of new therapies. TRIAL REGISTRATION: Netherlands Trial Register, NL7336, Date registered 11-10-2018.

Exhaled Breath Analysis for Investigating the Use of Inhaled Corticosteroids and Corticosteroid Responsiveness in Wheezing Preschool Children.

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

Forskolin-induced organoid swelling is associated with long-term cystic fibrosis disease progression.

RATIONALE: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC). METHODS: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed-effect models and multivariable logistic regression to estimate the association of FIS with long-term forced expiratory volume in 1 s % predicted (FEV1pp) decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC. RESULTS: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95% CI 0.11-0.54%; p=0.004) per 1000-point change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR 0.18, 95% CI 0.07-0.46; p<0.001), CF-related liver disease (adjusted OR 0.18, 95% CI 0.06-0.54; p=0.002) and diabetes (adjusted OR 0.34, 95% CI 0.12-0.97; p=0.044). These associations were absent for SCC. CONCLUSION: This study exemplifies the prognostic value of a patient-derived organoid-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences.

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

BACKGROUND: With the increased use of acid suppressants, significant potential complications such as community-acquired pneumonia (CAP) 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 CAP. Our main objective was to evaluate the risk of CAP in children using acid suppressants (proton pump inhibitors (PPIs) and/or histamine-2 receptor antagonists (H2RAs)). METHODS: We performed a cohort study using data from the UK 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 four unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of CAP. The cohort consisted of 84 868 exposed and 325 329 unexposed children. RESULTS: Current use of PPIs and H2RAs was associated with an increased risk of CAP (adjusted hazard ratio 2.05 (95% CI 1.90-2.22) and 1.80 (95% CI 1.67-1.94), respectively). The risk was even greater in patients with respiratory disease. Long-term use (≥211 days) of PPIs and H2RAs led to a significantly greater risk of CAP compared with short-term use (<31 days). After cessation of therapy, the risk remained increased for the following 7 months. CONCLUSION: The use of acid suppressants in children was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy.

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

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.

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.

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 H3O+, NO+ and O2+. Models were built with Linear Discriminant Analysis, Quadratic Discriminant Analysis, Soft Independent Modelling by Class Analogy, Partial Least Squares - Discriminant Analysis, K-Nearest Neighbours, and Classification and Regression Trees. Perfect models, concerning overall sensitivity and specificity (100% for both) were found using Direct Orthogonal Signal Correction (DOSC) pretreatment. Given the uncertainty related to the classification models associated with DOSC pretreatments (i.e. good classification found also for random classes), other models are built applying other preprocessing approaches. A Partial Least Squares - Discriminant Analysis model with a combined pre-processing method considering single value imputation results in 100% sensitivity and specificity for calibration, but was less good predictive. Pareto scaling prior to Quadratic Discriminant Analysis resulted in 41/55 correctly classified samples for calibration and 34/55 for cross-validation. In future, the uncertainty with DOSC and the applicability of the promising preprocessing methods and models must be further studied applying a larger representative data set with a more extensive number of samples for each class. Nevertheless, this pilot study showed already some potential for the untargeted SIFT-MS application as a rapid pattern-recognition technique, useful in the diagnosis of clinical breath samples.

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

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.

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

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

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

Abstract: Managing pediatric asthma includes optimizing both asthma control and asthma-specific quality of life (QoL). However, it is unclear to what extent asthma-specific QoL is related to asthma control or other clinical characteristics over time. The aims of this study were to assess in children longitudinally: (1) the association between asthma control and asthma-specific QoL and (2) the relationship between clinical characteristics and asthma-specific QoL. In a 12-month prospective study, asthma-specific QoL, asthma control, dynamic lung function indices, fractional exhaled nitric oxide, the occurrence of exacerbations, and the use of rescue medication were assessed every 2 months. Associations between the clinical characteristics and asthma-specific QoL were analyzed using linear mixed models. At baseline, the QoL symptom score was worse in children with asthma and concomitant chronic rhinitis compared to asthmatic children without chronic rhinitis. An improvement of asthma control was longitudinally associated with an increase in asthma-specific QoL (p-value < 0.01). An increased use of ß2-agonists, the occurrence of wheezing episodes in the year before the study, the occurrence of an asthma exacerbation in the 2 months prior to a clinical visit, and a deterioration of lung function correlated significantly with a decrease in the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) total score (p-values ≤ 0.01). Chronic rhinitis did not correlate with changes in the PAQLQ score over 1 year. The conclusion was that asthma control and asthma-specific QoL were longitudinally associated, but were not mutually interchangeable. The presence of chronic rhinitis at baseline did influence QoL symptom scores. ß2-agonist use and exacerbations before and during the study were inversely related to the asthma-specific QoL over time.

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

Objective: 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. Method: 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. Results: 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. Conclusion: (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.

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.

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/m2) 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.

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

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.

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

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.

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

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).

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

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.

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

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

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

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.

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

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.

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

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.