Background: Asthma is one of childhood’s most prevalent chronic conditions significantly impacting the quality of life. Current asthma management lacks real-time, objective, and longitudinal monitoring reflected by a high prevalence of uncontrolled asthma. Long-term home monitoring promises to establish new clinical endpoints for timely anticipation. In addition, integrating eHealth interventions holds promise for timely and appropriate medical anticipation for controlling symptoms and preventing asthma exacerbations. Objectives: This study aims to provide a pragmatic study design for gaining insight into longitudinal monitoring, assessing, and comparing eHealth interventions’ short- and long-term effects on improving pediatric asthma care. Design: The CIRCUS study design is a cohort multiple randomized controlled trial (cmRCT) with a dynamic cohort of 300 pediatric asthma patients. Methods: The study gathers observational and patient-reported measurements at set moments including patient characteristics, healthcare utilization, and asthma, clinical, and environmental outcomes. Participants are randomly appointed to the intervention or control group. The effects of the eHealth interventions are assessed and compared to the control group, deploying the CIRCUS outcomes. The participants continue in the CIRCUS cohort after completing the intervention and its follow-up. Results: This study was ethically approved by the Medical Research Ethics Committee (NL85668.100.23) on February 15th, 2024. Discussion: The CIRCUS study can provide a rich and unique dataset that can improve insight into risk factors of asthma exacerbations and yield new clinical endpoints. Furthermore, the effects of eHealth interventions can be assessed and compared with each other both short- and long-term. In addition, patient groups within the patient population can be discerned to tailor eHealth interventions to personalized needs on improving asthma management. Conclusion: In conclusion, CIRCUS can provide valuable clinical data to discern risk factors for asthma exacerbations, identify and compare effective scalable eHealth solutions, and improve pediatric asthma care. Trial registration : The protocol is registered at ClinicalTrials.gov (NCT06278662).

BACKGROUND:Childhood asthma is imposing a great financial burden on the pediatric health care system. Asthma costs are directly related to the level of asthma control. A substantial part of these costs may be preventable by the timely and adequate assessment of asthma deterioration in daily life and proper asthma management. The use of eHealth technology may assist such timely and targeted medical anticipation.OBJECTIVE:This paper describes the Ambulatory Pediatric Asthma Care (ALPACA) study protocol to investigate the effectiveness of an eHealth intervention consisting of remote patient monitoring and teleconsultation integrated into the daily clinical care of pediatric patients with asthma. This intervention aims to reduce health care utilization and costs and improve health outcomes compared to a control group that receives standard care. In addition, this study aims to improve future eHealth pediatric asthma care by gaining insights from home-monitoring data.METHODS:This study is a prospective randomized controlled effectiveness trial. A total of 40 participants will be randomized to either 3 months of eHealth care (intervention group) or standard care (control group). The eHealth intervention consists of remote patient monitoring (spirometry, pulse oximetry, electronic medication adherence tracking, and asthma control questionnaire) and web-based teleconsultation (video sharing, messages). All participants will have a 3-month follow-up with standard care to evaluate whether the possible effects of eHealth care are longer lasting. During the entire study and follow-up period, all participants will use blinded observational home monitoring (sleep, cough/wheeze sounds, air quality in bedroom) as well.RESULTS:This study was approved by the Medical Research Ethics Committees United. Enrollment began in February 2023, and the results of this study are expected to be submitted for publication in July 2024.CONCLUSIONS:This study will contribute to the existing knowledge on the effectiveness of eHealth interventions that combine remote patient monitoring and teleconsultation for health care utilization, costs, and health outcomes. Furthermore, the observational home-monitoring data can contribute to improved identification of early signs of asthma deterioration in pediatric patients. Researchers and technology developers could use this study to guide and improve eHealth development, while health care professionals, health care institutions, and policy makers may employ our results to make informed decisions to steer toward high-quality, efficient pediatric asthma care.TRIAL REGISTRATION:ClinicalTrials.gov NCT05517096; https://clinicaltrials.gov/ct2/show/NCT05517096.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):PRR1-10.2196/45585.

•EUFOREA asthma pocket guide is an educational and practical tool for non-respiratory physicians, paramedics and patients.•EUFOREA asthma pocket guide provides a simplified algorithm on asthma diagnosis, treatment and specialist referral.•EUFOREA asthma pocket guide is a living document which can be accessed at www.euforea.eu/news/asthma-pocket-guide.

Background eHealth monitoring technologies offer opportunities to more objectively assess symptoms when they appear in daily life. Asthma is the most common chronic disease in childhood with an episodic course, requiring close follow-up of pediatric asthma control to identify disease deterioration, prevent exacerbations, and enhance quality of life. eHealth technologies in pediatric asthma care show promising results regarding feasibility, acceptability, and asthma-related health outcomes. However, broad systematic evaluations of eHealth technologies in pediatric asthma are lacking. Objective The objective of this scoping review was to identify the types and applications of eHealth technologies for monitoring and treatment in pediatric asthma and explore which monitoring domains show the most relevance or potential for future research. Methods A scoping review was conducted using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. A systematic and comprehensive search was performed on English papers that investigated the development, validation, or application of eHealth technologies for home monitoring or treatment of pediatric asthma in the following databases: PubMed, Cochrane Library, IEEE, Scopus, CINAHL, PsycINFO, and ACM Digital Library. Two authors independently assessed eligibility and extracted data. Data were presented by a descriptive analysis of characteristics and a narrative report for each eHealth domain. Results The review included 370 manuscripts. The following 10 monitoring domains were identified: air quality, airway inflammation markers, lung function, physical activity, sleep, audiovisual, other physiological measurements, questionnaires, medication monitoring, and digital environment (ie, digital platforms, applications, websites, and software tools to monitor or support monitoring). Rising numbers of studies were seen, and the numbers accelerated in the last few years throughout most domains, especially medication monitoring and digital environment. Limited studies (35/370, 9.5%) of multiparameter monitoring strategies, using three or more domains, were found. The number of monitoring validation studies remained stable, while development and intervention studies increased. Intervention outcomes seemed to indicate the noninferiority and potential superiority of eHealth monitoring in pediatric asthma. Conclusions This systematic scoping review provides a unique overview of eHealth pediatric asthma monitoring studies, and it revealed that eHealth research takes place throughout different monitoring domains using different approaches. The outcomes of the review showed the potency for efficacy of most monitoring domains (especially the domains of medication monitoring, lung function, and digital environment). Future studies could focus on modifying potentially relevant hospital-based diagnostics for the home setting to investigate potential beneficial effects and focus on combining home-monitoring domains to facilitate multiparameter decision-making and personalized clinical decision support.

Exercise induced bronchial (EIB) constriction is a common and highly specific feature of pediatric asthma and should be diagnosed with an exercise challenge test (ECT). The impact of EIB in asthmatic children's daily lives is immense, considering the effects on both physical and psychosocial development. Monitoring childhood asthma by ECT's can provide insight into daily life disease burden and the control of asthma. Current guidelines for bronchoprovocation tests restrict both the use of reliever and maintenance asthma medication before an exercise challenge to prevent false-negative testing, as both have significant acute bronchoprotective properties. However, restricting maintenance medication before an ECT may be less appropiate to evaluate EIB symptoms in daily life when a diagnosis of asthma is well established. Rigorous of maintenance medication before an ECT according to guidelines may lead to overestimation of the real, daily life asthma burden and lead to an inappropiate step-up in therapy. The protection against EIB offered by the combined acute and chronic bronchoprotective effects of maintenance medication can be properly assessed whilst maintaining them. This may aid in achieving the goal of unrestricted participation of children in daily play and sports activities with their peers without escalation of therapy. When considering a step down in medication, a strategic wash-out of maintenance medication before an ECT aids in providing objective support of potential discontinuation of maintenance medication.

Exertional dyspnea is a common symptom in childhood which can induce avoidance of physical activity, aggravating the original symptom. Common causes of exertional dyspnea are exercise induced bronchoconstriction (EIB), dysfunctional breathing, physical deconditioning and the sensation of dyspnea when reaching the physiological limit. These causes frequently coexist, trigger one another and have overlapping symptoms, which can impede diagnoses and treatment. In the majority of children with exertional dyspnea, EIB is not the cause of symptoms, and in asthmatic children it is often not the only cause. An exercise challenge test (ECT) is a highly specific tool to diagnose EIB and asthma in children. Sensitivity can be increased by simulating real-life environmental circumstances where symptoms occur, such as environmental factors and exercise modality. An ECT reflects daily life symptoms and impairment, and can in an enjoyable way disentangle common causes of exertional dyspnea.

Introduction Asthma is one of the most common chronic diseases in childhood and is generally characterized by exercise induced bronchoconstriction (EIB). Assessing EIB is time consuming and expensive as it requires a fully equipped pulmonary function laboratory. Analysis of volatile organic compounds (VOCs) in breath is a novel technique for examining biomarkers which may associate with asthma features. The aim of this pilot study was to identify potential markers in the relationship between EIB and VOCs. Methods Children between four and 14 years old were asked to provide a breath sample prior to undergoing an exercise challenge test to assess for EIB. Results Breath samples were collected and analyzed in 46 asthmatic children, 21 with EIB and 25 without EIB (NO-EIB). Molecular features (MFs) were not significantly different between EIB and NO-EIB controls. 29 of the 46 children were corticosteroid naïve, 10 with EIB and 13 without. In the corticosteroid naïve group EIB was associated with increased MF23 and MF14 in the lower breath sample (p-value < 0.05). Conclusion This pilot study shows that EIB was related to an increased MF14 and MF23 in corticosteroid naïve children. The tentative identities of these compounds are octanal and dodecane/tetradecane respectively. These candidate biomarkers have a potential to enable non-invasive diagnosis of EIB in steroid-naïve children. Trial registration This study is registered in the Netherlands trial register (trial no. NL6087) at 14 February 2017.

Objective: Children with asthma who are physically active have a better quality of life, emphasizing the importance of activity monitoring and promotion in daily life. The validity of self-reported activity measurements has been questioned in pediatric populations. In this study, we aim to compare the Physical Activity Questionnaire for Children (PAQ-C) with objectively measured PA using accelerometry. Design: In this comparison study, the pooled dataset of two cross-sectional studies was used, which prospectively home-monitored PA using the alternative self-report PAQ-C questionnaire as well as with the criterion standard accelerometry (Actigraph wGT3X-BT and GT1M). Participants: Ninety children with pediatrician-diagnosed asthma participated in the study. Main Outcome Measures: Correlation coefficients were calculated to determine the relation between the PAQ-C and accelerometer data. The predictive value of the PAQ-C in differentiating between achieving and failing the recommended daily level of moderate-to-vigorous activity (MVPA) was evaluated with receiver operator characteristic (ROC) analysis. Results: The results showed weak to moderate correlations of the PAQ-C with the accelerometer data ( r = 0.29–0.47). A PAQ-C cutoff of 3.09 showed the best performance on predicting whether the recommended level of MVPA was achieved. With this cutoff, 21 of the 39 children that did achieve their daily MVPA level (53.8% sensitivity) and 33 of the 46 children that did fail their daily MVPA level (71.7% specificity) were correctly classified. A PAQ-C score of 3.5 revealed a negative predictive value of 100% for assessing physical inactivity. Conclusion: This study revealed a weak relation between the PAQ-C and PA assessed with accelerometry. However, a PAQ-C score of 3.5 or higher might be used as a low-cost and easy-to-use PA screening tool for ruling out physical inactivity in a portion of the pediatric asthma population. Clinical Trial Registration: Netherlands Trial Register: Trial NL6087.

Background Many asthmatic children suffer from uncontrolled asthma with frequent exacerbations, despite an optimal treatment plan using inhalation medication. Studies have shown that therapy adherence and inhalation technique are often suboptimal in asthmatic children, but these have traditionally been hard to measure. A novel device functioning as an add-on to the inhaler has been developed to measure both aspects by recording vibration patterns during inhalation. This data can be converted to smart feedback and provided to patients immediately via a mobile application. The aim of this study is to improve asthma control in children between 6 and 18 years old by providing immediate smart feedback on the intake of inhalation medication. Asthma control will be measured by forced expiratory volume in 1 s, (Childhood) Asthma Control Test ((c-)ACT) score, and lung function variability and reversibility. Methods The study will be performed in Medisch Spectrum Twente (Enschede, The Netherlands). The goal is to include 68 uncontrolled moderate to severe asthmatic children between 6 and 18 years old who receive controller inhalation medication through the Nexthaler®, Ellipta®, or Spiromax®. The study consists of three phases. Phase 1 is observational and will last 4 weeks to observe the baseline adherence and inhalation technique as monitored by the add-on device. A randomised controlled trial lasting 6 weeks will be performed in phase 2. Patients in the intervention group will receive immediate smart feedback about the performed inhalations via a mobile application. In the control group, adherence and inhalation technique will be monitored, but patients will not receive feedback. In phase 3, also lasting 6 weeks, the feedback will be ceased for all children and revision of current therapy may occur, depending on the findings in phase 2. Asthma control can be assessed by means of spirometry (both at home and in the hospital) and (c-)ACT questionnaires. Discussion Immediate smart feedback may improve therapy adherence and inhalation technique, and thus asthma control in children and prevent unnecessary switches to targeted biologics. Performing this study in children is desired, since they are known to react differently to feedback and medication than adults. Trial registration Dutch Trial Register NL7705 . Registered on 29 April 2019

Objective: Exercise-induced bronchoconstriction (EIB) is a highly prevalent morbidity of childhood asthma and defined by a transient narrowing of the airways during or after physical exercise. An exercise challenge test (ECT) is the reference standard for the diagnosis of EIB. Video evaluation of EIB symptoms could be a practical alternative for the assessment of EIB. We studied the ability of pediatricians to assess EIB from post-exercise videos. Methods: A clinical assessment was performed in 20 asthmatic children (mean age 11.6 years) and EIB was measured with a standardized ECT performed in cold, dry air. EIB was defined as a fall in forced expiratory volume in 1 s (FEV1) of ≥10% post-exercise. Children were filmed before and after exercise in frontal position and bare chested. The clinical assessment results and videos were shown to 20 pediatricians (mean experience 14.4 years). Each assessed EIB severity in 5 random children providing 100 assessments, scored on a continuous rating scale (0-10) and in severity classifications (no, mild, moderate, severe) using a scoring list including physical asthma symptoms. Correlations between predicted scores and objective scores were calculated with Spearman's rho and Cohen's Kappa. A generalized linear model was used to assess the relationship between physical symptoms and fall in FEV1. Results: Median fall in FEV1 after exercise was 15.1% (IQR 1.2-65.1). Pediatricians detected EIB with a sensitivity of 78% (95% CI 66-87%) and a specificity of 40% (95% CI 27-55%). The positive predictive value for a pediatricians' diagnosis of EIB was 61% (95% CI 50-72%). The negative predictive value was 60% (95% CI 42-76%). The agreement between predicted EIB severity classifications and the validated classifications based on the ECT's, was fair [Kappa = 0.36 (95% CI 0.23-0.48)]. The correlation between predicted EIB severity scored on a continuous rating scale and fall in FEV1 after exercise was weak (rs = 0.39, p < 0.001). Independent predictive variables for fall in FEV1 were wheezing (-11%), supraclavicular retractions (-8.4%) and a prolonged expiratory phase (-8.8%). Conclusion: The ability of pediatricians to assess EIB from post-exercise videos is fair at best, implicating that standardized ECT's are still vital in the assessment of EIB.

Exercise-induced bronchoconstriction (EIB) is a sign of uncontrolled childhood asthma and classically occurs after exercise. Recent research shows that EIB frequently starts during exercise, called breakthrough-EIB (BT-EIB). It is unknown whether this more severe type of EIB forces children to adapt their physical activity (PA) pattern in daily life. Therefore, this pilot study aims to investigate daily life PA (amount, intensity, duration, and distribution) in children with BT-EIB, 'classic' EIB, and without EIB. A Fitbit Zip activity tracker was used for one week to objectively measure daily life PA at one-minute intervals. Thirty asthmatic children participated. Children with BT-EIB were less physically active compared to children without EIB (respectively 7994 and 11,444 steps/day, p = .02). Children with BT-EIB showed less moderate-to-vigorous PA compared to the children without (respectively 117 and 170 minutes/day, p = .02). Children with EIB (both BT and classic) had significant shorter bouts of activity and a less stretched distribution of bout lengths compared to the non-EIB group (all p < .05). These results emphasize a marked association between EIB severity and PA patterns in daily life, stressing the need for a thorough clinical evaluation of exercise-induced symptoms in childhood asthma.

The COVID-19 crisis has pressured hospital-based care for children with high-risk asthma as they have become deprived of regular clinical evaluations. However, COVID-19 also provided important lessons about implementing novel directions for care. Personalized eHealth technology, tailored to the individual and the healthcare system, could substitute elements of hospital care and facilitate early and appropriate medical anticipation in response to imminent loss of control. This perspective article discusses new approaches to the clinical, organizational, and scientific aspects of the use of eHealth technology in pediatric asthma care in times of COVID-19, as illustrated by a case report of an acute asthma exacerbation possibly caused by COVID-19 infection.

Background Asthma is one of the most common chronic diseases in childhood, occurring in up to 10% of all children. Exercise-induced bronchoconstriction (EIB) is indicative of uncontrolled asthma and can be assessed using an exercise challenge test (ECT). However, this test requires children to undergo demanding repetitive forced breathing manoeuvres. We aimed to study the electrical activity of the diaphragm using surface electromyography (EMG) as an alternative measure to assess EIB. Methods Forty-two children suspected of EIB performed an ECT wearing a portable EMG amplifier. EIB was defined as a fall in FEV1 of more than 13%. Children performed spirometry before exercise, and at 1, 3 and 6 min after exercise until the nadir FEV1 was attained and after the use of a bronchodilator. EMG measurements were obtained between spirometry measurements. Results Twenty out of 42 children were diagnosed with EIB. EMG peak amplitudes measured at the diaphragm increased significantly more in children with EIB; 4.85 μV (1.82–7.84), compared to children without EIB; 0.20 μV (−0.10–0.54), (p<0.001) at the lowest FEV1 post-exercise. Furthermore, the increase in EMG peak amplitude could accurately distinguish between EIB and non-EIB using a cut-off of 1.15 μV (sensitivity 95%, specificity 91%). Conclusion EMG measurements of the diaphragm are strongly related to the FEV1 and can accurately identify EIB. EMG measurements are a less invasive, effort-independent measure to assess EIB and could be an alternative when spirometry is not feasible.

We have built and implemented a set of metaphors for breathing games by involving children and experts. These games are made to facilitate prevention of asthma exacerbation via regular monitoring of children with asthma through spirometry at home. To instruct and trigger children to execute the (unsupervised) spirometry correctly, we have created interactive metaphors that respond in real-time to the child's inhalation and exhalation. Eleven metaphors have been developed in detail. Three metaphors have been fully implemented based on current guidelines for spirometry and were tested with 30 asthmatic children. Each includes multi-target incentives, responding to three different target values (inhalation, peak expiration, and complete exhalation). We postulate that the metaphors should use separate goals for these targets, have independent responses, and allow to also go beyond expected values for each of these targets. From the selected metaphors, most children preferred a dragon breathing fire and a soccer player kicking a ball into a goal as a metaphor; least liked were blowing seeds of a dandelion and applying lotion to a dog to grow its hair. Based on this project we discuss the potential and benefits of a suite-of-games approach: multiple games that each can be selected and adapted depending on personal capabilities and interests.

Objective: Exercise-induced bronchoconstriction (EIB) is a specific morbidity of childhood asthma and an important sign of uncontrolled asthma. The occurrence of EIB is insufficiently identified by the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT). This study aimed to (1) evaluate the Visual Analog Scale (VAS) for dyspnea as a tool to detect EIB in asthmatic children and (2) assess the value of combining (C-)ACT outcomes with VAS scores. Methods: We measured EIB in 75 asthmatic children (mean age 10.8 years) with a standardized exercise challenge test (ECT) performed in cold and dry air. Children and parents reported VAS dyspnea scores before and after the ECT. Asthma control was assessed by the (C-)ACT. Results: Changes in VAS scores (Delta VAS) of children and parents correlated moderately with fall in forced expiratory volume in 1 second (FEV1), respectively r(s)=0.57 (p < .001) and r(s)=0.58 (p < .001). At a Delta VAS cutoff value of >= 3 in children, sensitivity and specificity for EIB were 80% and 79% (AUC 0.82). Out of 38 children diagnosed with EIB, 37 had a (C-)ACT score of <= 19 and/or a Delta VAS of >= 3, corresponding with a sensitivity of 97% and a negative predictive value of 96%. Conclusion: This study shows that the VAS could be an effective additional tool for diagnosing EIB in children. A reported difference in VAS scores of >= 3 after a standardized ECT combined with low (C-)ACT scores was highly effective in detecting and excluding EIB.

Introduction: Accurate and timely diagnosis of exercise induced bronchoconstriction (EIB) is important for disease management, especially in children. Exhaled Volatile Organic Compounds (VOCs) can reflect underlying disease activity in the airways potentially enabling non-invasive diagnosis. Objectives: In this cross-sectional study we investigated whether exhaled VOCs can discriminate between children with and without EIB. Methods: Exhaled breath was collected in 46 children with a clinical suspicion of EIB using the Breath Biopsy platform (Owlstone Medical). EIB was assessed at OCON sports-medical clinic by a standardised exercise challenge with pulmonary function testing prior to and after exercise. EIB was defined as a post-exercise drop in FEV1>13% (on ICS) or a >20% FEV1 reduction (ICS naïve). VOCs were extracted from the chromatogram and matched to library-IDs. Significantly discriminating VOCs were input into a Canonical Discriminant Analysis to subsequently generate a ROC-Curve with AUC value. Results: VOCs did not differentiate between EIB (n= 21, age 8.7±2.2yrs) and controls (n=25, age 8.4±3.1 years), AUC 0.42±0.31. Similar results were found in post-hoc analysis when limiting the analysis to subjects taking ICS (n=23, AUC 0.65±0.12). However, in ICS naïve subjects a significant difference was found (n=23, AUC 0.86±0.08), this was driven by 5 VOCs. Conclusions: Analysis of exhaled VOCs only discriminates patients with and without EIB if they are steroid naïve. Speculatively, this could be related to ICS related suppression of inflammation although results require confirmation in a larger study.

Objective: Heart rate variability (HRV) is a non-invasive measure of the interaction between the autonomic nervous system (ANS) and the cardiovascular system and an indicator of physiologic stress. HRV is proposed as an alternative biomarker to the effect of high flow nasal cannula (HFNC) therapy, a non-invasive ventilation mode, in children with severe respiratory disease. Approach: Seven children with severe acute respiratory disease were included in this pilot study. All of them received HFNC treatment. Standard physiological variables, such as heart rate (HR), breathing rate (BR) and blood oxygen saturation (SpO2) were analyzed during HFNC therapy. HRV, which includes the time domain parameters defined by the mean of RR intervals (avRR), the standard deviation of RR intervals (stdRR), the root mean square of differences between adjacent RR intervals (rmsSD), and the frequency domain parameters defined by spectral powers of low frequency (LF, 0.04 Hz-0.15 Hz) and high frequency (HF, 0.15 Hz-0.4 Hz) bands was also analysed during therapy. Main results: Only the time domain parameter rmsSD showed a significant increase (from 0.03 to 0.08 s, p < 0.05) between the middle and the end of the therapy. No significant changes were observed in HR, BR and SpO2 throughout the therapy. Of these three variables, only HR and BR showed a high and statistically significant positive correlation. Significance: HRV analysis seems to be a promising alternative biomarker to monitor the effect of HFNC therapy on children with severe respiratory disease.