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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.

Background: Long-COVID is a well-documented multisystem disease in adults. Far less is known about long-term sequelae of COVID in children. Here, we report on the occurrence of long-COVID in Dutch children. Patients and Methods: We conducted a national survey asking Dutch pediatricians to share their experiences on long-COVID in children. We furthermore describe a case series of six children with long-COVID to explore the clinical features in greater detail. Results: With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2–18 years, suspected of long-COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post-COVID complaints. Conclusion: Our study shows that long-COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management.

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

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

Background: Evaluation of lung function plays an important role in monitoring asthma and cystic fibrosis (CF) in children. Electronic home monitoring of lung function could be a helpful additional diagnostic tool to detect early changes in lung function. We investigated whether forced expiratory volume in 1 second (FEV1) measurements at home were comparable to FEV1 measurements during a clinical visit. Methods: We performed a re-analysis of prospectively collected data, which were collected in two previously performed one-year observational cohort studies of children with asthma and CF (RASTER and PREVEC studies). Measurements consisted of three maximal expiratory flow-volume maneuvers. FEV1 measurements were included if the measurement at home with an electronic home monitor (AM2+) was done on the same day as the FEV1 measurement on the clinical pneumotachometer (ZAN 100 spirometer) (2-monthly visits). Linear mixed model analysis was performed to estimate the overall mean difference (clinical measurement minus home measurement) in FEV1 values between these two methods, accounting for repeated measures within the same child. Results: In total 36 children with CF and 81 children with asthma met inclusion criteria. In CF the mean difference in FEV1 was 0.18 liters (L) (95% confidence interval (CI) 0.08-0.27 L; p Conclusion: FEV1 measurement at home (using a home monitor) on average resulted in significantly lower results than clinical FEV1 measurement with a pneumotachometer.

BackgroundWith 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)).MethodsWe 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.ResultsCurrent 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 (ConclusionThe 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.

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).

Background: In the past decade the measurement of volatile organic compounds (VOCs) in exhaled breath has gained widespread attention for the diagnosis and monitoring of various pulmonary diseases. Gas chromatography mass spectrometry (GC-MS) is currently considered the gold standard for VOCs analysis, albeit expensive and time-consuming. Recently, ion mobility spectrometry (IMS) has been introduced as a rapid and sensitive alternative to GC-MS. Studies using IMS for exhaled breath analysis in children are lacking. Aim: To evaluate diagnostic accuracy of exhaled breath analysis by IMS in differentiating between children with asthma, cystic fibrosis (CF), and healthy controls. Methods: We performed a cross-sectional study in 53 children ≥ 6 years of age (range 6-20 years). In 20 children with moderate to severe asthma, 12 children with CF, and 21 healthy controls, breath was analysed using a multicapillary column/ion mobility spectrometer (MCC/IMS; B&S Analytik, Dortmund, Germany). Results: In discriminating CF from healthy controls, 16 significant VOCs peaks were found of which one peak (P37) had highest diagnostic accuracy (accuracy 0.97, sensitivity 100%, specificity 95%, p Conclusion: This is the first study using IMS for breath analysis in children with asthma and CF. Diagnostic accuracy was high in discriminating CF from asthma and healthy controls, but poor in discriminating asthma from healthy controls.

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

A 3-month-old female infant was admitted with an infection of the left thumb after parental nail biting. A herpetic whitlow was diagnosed, although there were no signs of a herpes gingivostomatitis. Inoculation probably occurred through parental nail biting. Herpetic whitlow in young infants is rare and often misdiagnosed as a staphylococcal skin infection. It should be considered when an infection of the distal phalanx is accompanied by vesicles.

A 6-year-old girl presented with necrosis of the left labium minus. An encircled hair at the base of the lesion was seen, and the diagnosis genital hair tourniquet syndrome was made. Genital hair tourniquet syndrome in children is a rare but potentially severe syndrome that requires immediate medical attention to prevent resulting necrosis.