Remote Patient Monitoring and Teleconsultation to Improve Health Outcomes and Reduce Health Care Utilization of Pediatric Asthma (ALPACA Study): Protocol for a Randomized Controlled Effectiveness Trial.

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.

eHealth Technologies for Monitoring Pediatric Asthma at Home: Scoping Review.

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.

An Algorithm for Strategic Continuation or Restriction of Asthma Medication Prior to Exercise Challenge Testing in Childhood Exercise Induced Bronchoconstriction.

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.

Can the Childhood Physical Activity Questionnaire Be Used to Identify Physical Activity Levels in Children With Asthma?

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.

The Need for Testing-The Exercise Challenge Test to Disentangle Causes of Childhood Exertional Dyspnea.

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.

COVID-19: Technology-Supported Remote Assessment of Pediatric Asthma at Home.

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.

Does immediate smart feedback on therapy adherence and inhalation technique improve asthma control in children with uncontrolled asthma? A study protocol of the IMAGINE I study.

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.

Assessing paediatric exercise-induced bronchoconstriction using electromyography.

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 FEV 1 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 FEV 1 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.

Assessing Exercise-Induced Bronchoconstriction in Children; The Need for Testing.

Objective: Exercise-induced bronchoconstriction (EIB) is a specific morbidity of childhood asthma and a sign of insufficient disease control. EIB is diagnosed and monitored based on lung function changes after a standardized exercise challenge test (ECT). In daily practice however, EIB is often evaluated with self-reported respiratory symptoms and spirometry. We aimed to study the capacity of pediatricians to predict EIB based on information routinely available during an outpatient clinic visit. Methods: A clinical assessment was performed in 20 asthmatic children (mean age 11.6 years) from the outpatient clinic of the MST hospital from May 2015 to July 2015. During this assessment, video images were made. EIB was measured with a standardized ECT performed in cold, dry air. Twenty pediatricians (mean years of experience 14.4 years) each evaluated five children, providing 100 evaluations, and predicted EIB severity based on their medical history, physical examination, and video images. EIB severity was predicted again after additionally providing baseline spirometry results. Results: Nine children showed no EIB, four showed mild EIB, two showed moderate, and five showed severe EIB. Based on clinical information and spirometry results, pediatricians detected EIB with a sensitivity of 84% (95% CI 72-91%) and a specificity of 24% (95% CI 14-39%).The agreement between predicted EIB severity classifications and the validated classifications after the ECT was slight [Kappa = 0.05 (95% CI 0.00-0.17)]. This agreement still remained slight when baseline spirometry results were provided [Kappa = 0.19 (95% CI 0.06-0.32)]. Conclusion: Pediatricians' prediction of EIB occurrence was sensitive, but poorly specific. The prediction of EIB severity was poor. Pediatricians should be aware of this in order to prevent misjudgement of EIB severity and disease control.

Effects of dietary induced weight loss on exercise-induced bronchoconstriction in overweight and obese children.

RATIONALE: Previous studies showed that obesity in asthmatic children is associated with more severe exercise-induced bronchoconstriction (EIB), compared with non-obese asthmatic children. This study investigates the effect of weight loss on EIB in overweight and obese asthmatic children. METHODS: In this intervention study, children aged 8-18 years with EIB and moderate to severe overweight, followed a diet based on healthy daily intake for 6 weeks. Before and after the diet period they underwent an exercise challenge test in cold air. Primary outcome was change in exercise-induced fall in FEV1 and relation between weight loss and EIB. Secondary outcomes were changes in recovery of FEV1 ("area under the curve"; AUC), fraction of exhaled nitric oxide (FeNO) and scores of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and Asthma Control Questionnaire (ACQ). RESULTS: Twenty children completed the study. After the diet period, weight, and body mass index (BMI) were significantly reduced (changes respectively -2.6% and -1.5 kg/m(2), P < 0.01). There was a significant improvement of the percentage exercise-induced fall in FEV1 (30.6% vs. 21.8%, P < 0.01), AUC and PAQLQ score. The reduction in BMI z-score was significantly related to the reduction in the percentage exercise-induced fall in FEV1 in children that lost weight (r = 0.53, P = 0.03). There were no changes in FeNO and ACQ. CONCLUSIONS: Dietary induced weight loss in overweight and obese asthmatic children leads to significant reduction in severity of EIB and improvement of the quality of life. The reduction in BMI z-score is significantly related to the improvement of EIB.

Inspiratory airflow limitation after exercise challenge in cold air in asthmatic children.

Methacholine and histamine can lead to inspiratory flow limitation in asthmatic children and adults. This has not been analyzed after indirect airway stimuli, such as exercise. The aim of the study was to analyze airflow limitation after exercise in cold, dry air. 72 asthmatic children with mild to moderate asthma (mean age 13.2 ± 2.2 yrs) performed a treadmill exercise challenge. A fall of >10% in FEV(1) was the threshold for expiratory flow limitation and a fall of >25% of MIF(50) was the threshold for inspiratory flow limitation. The occurrence of wheeze, stridor and cough were quantified before and after exercise. After exercise, the mean fall in FEV(1) was 17.7 ± 14.6%, while the mean fall in MIF(50) was 25.4 ± 15.8%; no correlation was found between fall in FEV(1) and MIF(50) (R(2): 0.04; p = 0.717). 53 of the 72 children showed an inspiratory and/or expiratory airflow limitation. 38% (20/53) of these children showed an isolated expiratory flow limitation, 45% (24/53) showed both expiratory and inspiratory flow limitation and 17% (9/53) showed an isolated inspiratory flow limitation. The fall in FEV(1) peaked 9 min after exercise and correlated to expiratory wheeze. The fall in MIF(50) peaked 15 min after exercise and correlated to inspiratory stridor. The time difference in peak fall between FEV(1) and MIF(50) was statistically significant (5.9 min; p < 0.001, 99% CI: 2.3-9.5 min). In conclusion, this study shows that an exercise challenge in asthmatic children can give rise to inspiratory airflow limitation, which may give rise to asthma like symptoms.

Equal virulence of rhinovirus and respiratory syncytial virus in infants hospitalized for lower respiratory tract infection.

Respiratory syncytial virus (RSV) and rhinovirus (RV) are predominant viruses associated with lower respiratory tract infection in infants. We compared the symptoms of lower respiratory tract infection caused by RSV and RV in hospitalized infants. RV showed the same symptoms as RSV, so on clinical grounds, no difference can be made between these pathogens. No relation between polymerase chain reaction cycle threshold value and length of hospital stay was found.

Monitoring pulmonary function during exercise in children with asthma.

OBJECTIVE: Exercise-induced bronchoconstriction (EIB) is defined as acute, reversible bronchoconstriction induced by physical exercise. It is widely believed that EIB occurs after exercise. However, in children with asthma the time to maximal bronchoconstriction after exercise is short, suggesting that the onset of EIB in such children occurs during exercise. AIM: In this study the authors investigate pulmonary function during exercise in cold air in children with asthma. METHODS: 33 Children with asthma with a mean age of 12.3 years and a clinical history of exercise induced symptoms, underwent a prolonged, submaximal, exercise test of 12 min duration at approximately 80% of the predicted maximum heart rate. Pulmonary function was measured before and each minute during exercise. If EIB occurred (fall in forced expiratory volume in 1 s >15% from baseline), exercise was terminated and salbutamol was administered. RESULTS: 19 Children showed EIB. In 12 of these children bronchoconstriction occurred during exercise (breakthrough EIB), while seven children showed bronchoconstriction immediately after exercise (non-breakthrough EIB). Breakthrough EIB occurred between 6 and 10 min of exercise (mean 7.75 min). CONCLUSION: In the majority of children with EIB in this study (ie, 12 out of 19), bronchoconstriction started during, and not after, a submaximal exercise test.

Association of the asthma control questionnaire with exercise-induced bronchoconstriction.

INTRODUCTION: Asthma is a common chronic disease in childhood which features bronchial hyperresponsiveness to exercise (EIB). In daily clinical practice, the report of EIB is used to assess the level of control of asthma. The asthma control questionnaire (ACQ) is a tool to evaluate the control of asthma in children. The aim of this study was to evaluate the relationship between the ACQ and EIB. MATERIALS AND METHODS: Two hundred children, aged 12.5 ± 2.5 years, with a pediatrician-diagnosed mild-to-moderate asthma filled out an ACQ and performed an exercise provocation test in cold air. EIB was defined as a fall in FEV(1) of 15%. RESULTS: Eighty six of the 200 children had a positive exercise challenge. There was no relationship between the categorical ACQ and the occurrence of EIB (p = .39). There was no difference in the occurrence of EIB between genders (p = .12). The positive predictive value of the ACQ for EIB was 51% and the negative predictive value for EIB was 59%. In comparison to the girls, the boys carried an odds ratio (OR) of 0.48 for having an indifferent control of asthma (p = .04; confidence interval (CI): 0.23-0.96), and an OR of 0.46 for having a not well-controlled asthma (p = .03; CI: 0.23-0.93). CONCLUSION: This study shows that the ACQ is not related to EIB in children with asthma. Remarkable is the percentage (41%) of children who, despite well-controlled asthma according to the ACQ, had EIB, which implies that their asthma is not well-controlled. Boys were more likely to report well-controlled asthma, although boys and girls were equally likely to have EIB.