Analyzing exhaled breath for volatile organic compounds (VOCs) using thermal desorption–gas chromatography–mass spectrometry (TD-GC-MS) offers a non-invasive diagnostic approach for various diseases. Despite its promise, the method faces challenges like sampling heterogeneity and high costs. Following the European Respiratory Society’s advocacy for methodological standardization, we developed the SPIRITAS (Standardized Product for Inexpensive Respiratory InvesTigation: A breath Sampler), a low-cost, disposable breath sampler. This study evaluates the SPIRITAS’s effectiveness in detecting targeted VOCs. We tested the SPIRITAS using the Peppermint Experiment, a standardized protocol that allows for comparison between different breath sampling and analytical practices by assessing the ability to detect five peppermint-specific VOCs after ingestion of a 200-milligram peppermint oil capsule. We included ten subjects and performed six breath samples per participant, including a baseline measurement taken before ingestion. We used the Wilcoxon signed-rank test to evaluate whether baseline values were significantly lower than the peak values of the targeted VOCs. Additionally, we conducted an experiment utilizing humidified medical-grade air to identify any VOCs attributable to the SPIRITAS setup itself. Results showed successful detection of four out of five targeted “peppermint-associated” VOCs: alpha-pinene (p ≤ 0.01), beta-pinene (p ≤ 0.01), menthone (p = 0.01), and menthol (p = 0.02), indicating significant differences between the baseline and peak values in the volunteers’ breath. However, detection of eucalyptol was inconsistent. In addition, we identified 16 VOCs that were released by the SPIRITAS, one of which remains unidentified. Our findings underscore the SPIRITAS’s potential for clinical applications, paving the way for broader biomarker research. The combination of ease of use, low cost, reduced risk of contamination, and standardization makes SPIRITAS very suitable for large-scale international studies. Furthermore, we have demonstrated the SPIRITAS’s effectiveness in detecting specific VOCs and identified 16 compounds originating from the SPIRITAS, ensuring that these compounds would not be mis-qualified as potential biomarkers in future clinical studies.

Background & objectives: Despite the availability of biologics for severe pediatric asthma, real‐life studies reporting on drivers behind initiating biologics and their alignment with the Global Initiative for Asthma (GINA) recommendations are lacking.Methods: We performed analysis within the pediatric asthma noninvasive diagnostic approaches study, a prospective cohort of 6‐ to 17‐year‐old children with severe asthma. Information was collected on demographic factors, symptom control, treatment, comorbidities, and diagnostic tests from medical records and questionnaires. We divided patients into “starters” or “nonstarters” based on the clinical decision to initiate biologics and performed multivariate logistic regression analysis to identify drivers behind initiating therapy. Additionally, we assessed patient suitability for biologics according to key factors in the GINA recommendations: Type 2 inflammation, frequency of exacerbations, and optimization of treatment adherence.Results: In total, 72 children (mean age 11.5 ± 3.0 years, 65.3% male) were included (13 starters). Initiation of biologics was associated with a higher GINA treatment step (adjusted odds ratio's [aOR] = 5.0, 95%CI 1.33–18.76), steroid toxicity (aOR = 21.1, 95%CI 3.73–119.91), frequency of exacerbations (aOR = 1.6, 95%CI 1.10–2.39), improved therapy adherence (aOR = 1.7, 95%CI 1.10–2.46), Caucasian ethnicity (aOR = 0.20, 95%CI 0.05–0.80), ≥1 allergic sensitization (aOR = 0.06, 95%CI 0.004–0.97), and allergic rhinitis (aOR = 0.13, 95%CI 0.03–0.65). Furthermore, steroid toxicity was identified as an important factor for deviation from the current recommendations on biologic prescription.Conclusions: We identified multiple drivers and inhibitors for initiating biologics, and showed the clinical need for biologics in severe pediatric asthmatics suffering from steroid toxicity. These findings may help refine asthma management guidelines.

Background: Severe acute asthma (SAA) in children can be life-threatening. There has been a significant rise in paediatric intensive care unit (PICU) admissions due to SAA over the past two decades. While asthma is a heterogeneous disease, its underlying pathophysiological pathways remain underexplored. This study aimed to assess the value of non-invasive targeted exhaled breath metabolomics analysis to better characterise SAA. Methods: Breath samples from 17 children admitted to the PICU with SAA (cases) and 27 children with controlled severe asthma (controls) were analysed using thermal desorption gas chromatography–mass spectrometry (TD-GC-MS). Results: A targeted volatile organic compound (VOC) analysis identified 25 compounds, of which 16 were shared between groups. Four VOCs were significantly more often present in SAA, and nine VOCs exhibited higher concentrations in SAA. Longitudinal analysis of VOCs from follow-up samples of 10 cases showed no significant temporal differences, reinforcing the reproducibility of identified biomarkers. Conclusions: This study exemplifies the potential of exhaled breath analysis to provide insights into the molecular background of SAA. Breath metabolomics may enable early recognition of severe asthma attacks and preventive therapeutic interventions in children with severe asthma.

Background: Fatigue is a commonly reported clinical symptom, yet research on fatigue in children with severe asthma is missing. We aimed to explore the extent of fatigue in severe pediatric asthma and identify associated factors.Method: This study was conducted within the Pediatric Asthma Non‐Invasive Diagnostic Approaches (PANDA), an observational cohort of 6‐ to 17‐year‐old Dutch children with severe asthma. The Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL™‐MFS) was used to measure self‐reported fatigue. Fatigue levels were compared with a general pediatric Dutch population using linear regression, and quantifying the prevalence of “fatigued” (−2 < Standard deviations [SD] ≤ −1) and “severely fatigued” (SD ≤ −2) children. Secondly, we performed linear regression analyses to explore whether fatigue levels were independently associated with asthma attacks, comorbidities, medication, pulmonary function, symptom control, and asthma‐related quality of life (QoL).Results: Severe pediatric asthma patients (n = 78, mean age 11.8 ± 3.1 years) reported significantly more fatigue than Dutch peers (n = 328, mean age 11.8 ± 3.2 years) mean difference in z‐score: −0.68; 95%CI −0.96, −0.40. In the severe asthma group, 28.2% scored as “fatigued” and 15.4% as “severely fatigued,” compared with 14.0% and 3.4% in the general population. In pediatric asthma patients, asthma‐related QoL (β = 0.77, p < .01, ΔR² = .43), symptom control (β = 0.56, p < .01, ΔR² = .24) and a dysfunctional breathing pattern (β = −0.36, p < .01, ΔR² = .12) were most strongly associated with fatigue scores.Conclusion: Fatigue is a common symptom in children with severe asthma and is associated with multiple clinical factors and patient‐reported outcomes. It should be considered as an important treatment target.

Background: For children with refractory difficult asthma achieving adequate control can be challenging. Previously we have shown that multidisciplinary inpatient treatment improves short-term asthma control and quality of life for patients that remain uncontrolled despite optimal outpatient treatment by paediatric pulmonologists. Objective: To evaluate the long-term effects of multidisciplinary inpatient treatment in paediatric patients with refractory difficult asthma. Methods: In this prospective observational study, 10 children (mean age 12.3 ± 2.3 years) hospitalised in Asthma Centre Merem, Netherlands (mean treatment duration 4.4 ± 0.5 weeks) were followed up for 12-24 months (mean 17.6 ± 4.3). Treatment focused on optimizing basic management by addressing four modules; asthma specific, physical health, chronical illness and system therapy. Evaluations were taken prior admission and post treatment. Statistical significance on intra-individual change in outcome variables was assessed using the Wilcoxon signed rank test. Results: Overall there was a significant reduction in hospital admissions (p. 0.018), emergency room visits (p. 0.021) and oral corticosteroid use (p. 0.007) comparing 12 months prior and post treatment. In addition treatment had positive effect on school attendance; children with < 1 month of school absenteeism increased from 10% (pre-treatment) to 90% (post-treatment). Improvements in asthma related quality of life (PAQLQ) exceeded the clinically minimal important difference; mean pre-treatment 5.5 ± 0.8 vs post treatment 6.5 ± 0.5. Conclusion: This small observational study shows that multidisciplinary inpatient treatment can have long-term effects in several aspects of asthma control and quality of life.

Introduction: Biologics have been shown to reduce exacerbation-rate and improve quality of life in children with severe asthma. However, real-life studies in children are scarce and there is still a substantial non-response rate. Aim: Compare clinical characteristics at baseline and response rates after 6 months between children identified by paediatric pulmonologists to start a biologic (starters) and who were not (non-starters). Methods: We performed an analysis in the Paediatric-Asthma-Non-Invasive-Diagnostic-Approaches (PANDA) study on children with severe asthma 6-17 years; treated according to Global Initiative for Asthma step ≥ 4). Differences in clinical characteristics were explored at baseline and a composite score consisting of number of oral corticosteroids (OCS) courses, lung function (FEV1post-BD%pred), Asthma-Control-Test (ACT) and Paediatric-Asthma-Quality-of-Life-Questionnaire (PAQLQ), was used to measure response rates after 6 months. Results: 31 children (mean age 11.1±2.9 years, 68% male) were included, of whom 10 starters. Starters were less often Caucasian (p.0.02), had a better therapy adherence (p.0.007) measured by Medication-Adherence-Report-Scale (MARS-5), a lower FEV1post-BD%pred (p.0.02) and higher OCS-use (p.0.03). 17 children completed the six-month follow-up, of which 6 starters. The response rate in starters was 50%, whereas 82% of the non-starters showed respons. Conclusion: Exacerbation-rate, therapy adherence, ethnicity and lung function seem to be determinative factors in the decision making process of starting a biological. Furthermore, response rate is still suboptimal, underlining the importance of identifying new (bio)markers for prediction of response.