Volatile organic breath components and exercise induced bronchoconstriction in asthmatic children.

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.

WEARCON: wearable home monitoring in children with asthma reveals a strong association with hospital based assessment of asthma control.

BACKGROUND: Asthma is one of the most common chronic diseases in childhood. Regular follow-up of physiological parameters in the home setting, in relation to asthma symptoms, can provide complementary quantitative insights into the dynamics of the asthma status. Despite considerable interest in asthma home-monitoring in children, there is a paucity of scientific evidence, especially on multi-parameter monitoring approaches. Therefore, the aim of this study is to investigate whether asthma control can be accurately assessed in the home situation by combining parameters from respiratory physiology sensors. METHODS: Sixty asthmatic and thirty non-asthmatic children were enrolled in the observational WEARCON-study. Asthma control was assessed according to GINA guidelines by the paediatrician. All children were also evaluated during a 2-week home-monitoring period with wearable devices; a physical activity tracker, a handheld spirometer, smart inhalers, and an ambulatory electrocardiography device to monitor heart and respiratory rate. Multiple logistic regression analysis was used to determine which diagnostic measures were associated with asthma control. RESULTS: 24 of the 27 uncontrolled asthmatic children and 29 of the 32 controlled asthmatic children could be accurately identified with this model. The final model showed that a larger variation in pre-exercise lung function (OR = 1.34 95%-CI 1.07-1.68), an earlier wake-up-time (OR = 1.05 95%-CI 1.01-1.10), more reliever use (OR = 1.11 95%-CI 1.03-1.19) and a longer respiratory rate recovery time (OR = 1.12 95%-CI 1.05-1.20) were significant contributors to the probability of having uncontrolled asthma. CONCLUSIONS: Home-monitoring of physiological parameters correlates with paediatrician assessed asthma control. The constructed multivariate model identifies 88.9% of all uncontrolled asthmatic children, indicating a high potential for monitoring of asthma control. This may allow healthcare professionals to assess asthma control at home. TRIAL REGISTRATION: Netherlands Trail Register, NL6087 . Registered 14 February 2017.

The Visual Analog Scale detects exercise-induced bronchoconstriction in children with asthma.

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 (ΔVAS) of children and parents correlated moderately with fall in forced expiratory volume in 1 second (FEV1), respectively rs=0.57 (p < .001) and rs=0.58 (p < .001). At a ΔVAS 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 ΔVAS 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.

Can Pediatricians Assess Exercise-Induced Bronchoconstriction From Post-exercise Videos?

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.

Effects of a single dose inhaled corticosteroid on the dynamics of airway obstruction after exercise.

RATIONALE: Exercise-induced bronchoconstriction (EIB) is defined as a transient narrowing of the airways induced by exercise. Repetitive measurements of spirometric parameters, such as FEV(1) and expiratory flows, and forced oscillation technique (FOT) measurements can be used to analyze the dynamics of EIB. A single high dose of fluticasone propionate (FP) protects against EIB. The aim of the study was to analyze the effect of FP on the dynamics of exercise-induced airway narrowing as measured with FOT and spirometry. METHODS: Twelve children performed an exercise challenge on 2 separate days, 4 hr after inhalation of 1 mg FP (pressurized metered dose inhaler) or a placebo. Before and after the exercise flow-volume loops as well as the FOT (frequency range: 4-32 Hz) were measured. RESULTS: The FEV(1) , and FEF(50) fell significantly after exercise within groups; the peak fall in FEV(1) after FP was significantly smaller than after placebo (respectively, 19.3 ± 14.6% and 29.2 ± 14.8%, P = 0.03, 95% CI: 0.9-18.8%). The fall in FEV(1) and FEF(50) peaked 3 min after exercise and showed a subsequent partial recovery. The fall in the FEV(1) /FVC ratio showed a later peak fall (12 min after exercise). The resistance increased while the reactance decreased significantly after exercise. FP significantly decreased the maximal increase in Rrs(6) when compared to the placebo (respectively 176.5 ± 59.1% and 201.0 ± 63.8%, P = 0.05, 95% CI: 0.5-48.7%). The maximal decrease in Xrs(6) was not significantly affected by FP (P = 0.06). CONCLUSION: Repetitive spirometric and FOT measurements after exercise show a rapid narrowing and steady recovery of the patency of the conducting airways, and indicate a delayed and prolonged recovery of the smaller airways. A single high dose of inhaled FP seems to employ its effect mainly in the conducting airways.

Pilot study: The effect of reducing treatment on exercise induced bronchoconstriction.

UNLABELLED: SUMMARY RATIONALE: Asthma therapy should be stepped up or stepped down in response to changes in asthma control. However, there is little evidence available on the optimal timing, sequence, and degree of medication reductions. In this study we analyzed clinically stable asthmatic children who underwent a medication reduction from a combination preparation consisting of an inhaled corticosteroid (ICS) and long acting beta2-agonist (LABA) to monotherapy with the same dose of the ICS. We hypothesized that the extent of exercise-induced bronchoconstriction (EIB) would not increase after the cessation of the LABA. METHODS: Nineteen children, aged 8-16 years, with clinically stable asthma, receiving LABA/ICS combination therapy, were analyzed in this open-label pilot study. Children performed an exercise challenge at baseline and 3 weeks after the medication reduction. Best values of spirometric measurements of the forced expiratory volume in 1 sec (FEV(1)) were used for statistical calculations. RESULTS: Maximum percent fall in FEV(1) was significantly lower after 3 weeks of ICS monotherapy (P = 0.03). Eight of 19 children had a >or=15% fall in FEV(1) after exercise at the initial exercise challenge. In this subgroup, maximum percent fall in FEV(1) after the medication reduction was significantly lower (P < 0.01), and in six children it decreased to <15%, indicating they no longer had EIB. CONCLUSION: In clinically stable asthmatic children on LABA/ICS combination therapy, the cessation of the LABA can reduce and in most cases abolish EIB.