OBJECTIVE: Relvar® (fluticasone furoate [FF]/vilanterol [VI]) is a once-daily inhaler with bronchodilator effect lasting 24 h. Our aim was to investigate the short- and long-term effects of FF/VI on exercise-induced asthma (EIA) in adolescents.
METHODS: Ninety-three adolescent asthmatics aged 12-18 years were referred for evaluation of EIA. Following a positive exercise challenge test (ECT), 22/44 were allocated to a single administration of salbutamol (400 μg) and 22/44 to FF/VI (92/22 μg) in a double-blind method. Thirty-five subjects were reassessed by repeat ECT 30-60 days of FF/VI.
RESULTS: Median FEV1 change post-ECT at baseline was -22.8% predicted (interquartile range [IQR] -26.1 and -18.0) for salbutamol and -21.0 (IQR -30.7 and -16.8) for FF/VI. Following bronchodilator, FEV1 improved similarly in both groups. Repeat ECT following 30-60 days of FF/VI resulted in negative ECT in 33/35 subjects; the median decrease in FEV1 of these 35 subjects was 22.6% predicted (IQR 29-18) before, and 4.6% predicted (IQR 8.7-2.5) after 30-60 days of FF/VI treatment (p < 0.0001).
CONCLUSIONS: FF/VI is effective in reversing EIA after 15 min in adolescents and in protecting EIA after 30-60 days in adolescents. Larger studies are needed to assess the effect of FF/VI on EIA.

The impact of sickle cell anemia (SCA) and its complications on physical functioning and cardiopulmonary/aerobic fitness in affected individuals is significant. Although limited data support the safety of maximal cardiopulmonary exercise testing (CPET) for children and adults with SCA, the safety of submaximal moderate and high intensity, and longer duration, exercise in this population is not clear. The Sickle Cell Pro-Inflammatory Response to Interval Testing Study (SPRINTS) is a multicenter, randomized, prospective trial. SPRINTS leverages unique collaborations between investigators in pediatric hematology and exercise science to evaluate the impact of exercise intensity on the acute phase inflammatory response to exercise and changes in airway dynamics in children and young adults with SCA. Here we describe the study design and methodological strategies employed in SPRINTS, including an exercise challenge that mimics real-life patterns of childhood physical activity, characterized by multiple moderate and high intensity brief bouts of exercise interspersed with rest periods. Primary outcomes comprise pre- and post-exercise biomarkers of inflammation and endothelial dysfunction and spirometry. Secondary outcomes include assessment of physical activity and functioning, genomic studies and near-infrared spectroscopy measurements to assess tissue oxygenation status during exercise. SPRINTS aims to enroll 70 subjects with SCA and 70 matched, healthy controls. We anticipate that data from SPRINTS will address gaps in our understanding of exercise responses and safety in SCA and support the future development of evidence-based, exercise prescription guidelines in this population.

BACKGROUND: It has been documented that aerobic exercise may increase pulmonary functions and aerobic capacity, but limited data has evaluated a child\'s satisfaction and pediatric quality of life (PQoL) with exercise training.
OBJECTIVE: This study aimed to investigate the effects of moderate-intensity exercise training on asthmatic school-aged children.
METHODS: This study included 38 school-aged children with asthma (23 males and 15 females) aged between 8-12 years. They were randomly assigned to two groups, aerobic exercise (AE) and conventional treatment (Con ttt) groups. The AE group received a program of moderate-intensity aerobic exercise for 10 weeks with asthma medications and the Con ttt group received only asthma medications without exercise intervention. A home respiratory exercise was recommended for the two groups. Aerobic capacity was investigated using maximal oxygen uptake (VO2max), 6-minute walk test (6MWT), and fatigue index. PQoL was evaluated using Pediatric Quality of Life Questionnaire (PQoLQ). Also, pulmonary function tests were performed, and the results recorded.
RESULTS: The findings of this study showed significant improvements in pulmonary functions and VO2max in the two groups; however, this improvement was significantly higher in the AE group than in the Con ttt group (p<0.05). The 6MWT and fatigue index improved in the AE group (p<0.05) but not in the Con ttt group (p>0.05). All dimensions of PQoL significantly improved in the AE group (p<0.05), but there was no significant improvement in the Con ttt group after the 10-week intervention period (p>0.05).
CONCLUSIONS: Ten weeks of physical exercise had beneficial effects on pulmonary functions, aerobic capacity, and PQoL in school-aged children with asthma. Effort and awareness should be dedicated to encouraging the active lifestyle among different populations, especially asthmatic children.

OBJECTIVE: The diagnosis of exercise-induced bronchoconstriction (EIB) was established by changes in lung function after exercise challenge. The prevalence of EIB and factors related to EIB were not fully described in children with asthma. The aim of this study was to investigate the prevalence and predictors of EIB in children with asthma.
METHODS: A total of 149 children with physician-diagnosed asthma above 5 years of age underwent standardized treadmill exercise challenge for EIB and methacholine challenge for airway hyper-responsiveness from October 2015 to December 2016.
RESULTS: EIB presented in 52.5% of children with asthma. Compared with children without EIB, there were more patients with atopic dermatitis in children with EIB (p = 0.038). Allergic to Dermatohagoides pteronyssinus and Dermatophagoides farinae were also found more in children with EIB (p = 0.045 and 0.048 respectively). Maximal decrease in forced expiratory volume in 1 s (FEV1) were highest in patients who were most sensitive to methacholine provocation (provocation concentration causing 20% fall in FEV1 [PC20] ≤ 1 mg/mL). Patients, who were more sensitive to methacholine challenge (with lower PC20 levels), develop EIB with more decline in FEV1 after exercise challenge (p = 0.038). Among patients with EIB, airflow limitation development in patient with methacholine-induced airway hyper-responsiveness was more abrupt and severe compared with patients without airway hyper-responsiveness (p = 0.045 and 0.033 respectively).
CONCLUSIONS: EIB presented in 52.5% of children with asthma. The more severe methacholine-induced hyper-responsiveness, the higher prevalence of EIB as well as the severity.

This study aimed to compare the performance of a semiautomated ventilation defect segmentation approach, adaptive K-means, with manual segmentation of hyperpolarized helium-3 magnetic resonance imaging in subjects with exercise-induced bronchoconstriction (EIB).
Six subjects with EIB underwent hyperpolarized helium-3 magnetic resonance imaging and spirometry tests at baseline, post exercise, and recovery over two separate visits. Ventilation defects were analyzed by two methods. First, two independent readers manually segmented ventilation defects. Second, defects were quantified by an adaptive K-means method that corrected for coil sensitivity, applied a vesselness filter to estimate pulmonary vasculature, and segmented defects adaptively based on the overall low-intensity signals in the lungs. These two methods were then compared in four aspects: (1) ventilation defect percent (VDP) measurements, (2) correlation between spirometric measures and measured VDP, (3) regional VDP variations pre- and post exercise challenge, and (4) Dice coefficient for spatial agreement.
The adaptive K-means method was ~5 times faster, and the measured VDP bias was under 2%. The correlation between predicted forced expiratory volume in 1 second over forced vital capacity and VDP measured by adaptive K-means (ρ = -0.64, P <0.0001) and by the manual method (ρ = -0.63, P <0.0001) yielded almost identical 95% confidence intervals. Neither method of measuring VDP indicated apical/basal or anterior dependence in this small study cohort.
Compared to the manual method, the adaptive K-means method provided faster, reproducible, comparable measures of VDP in EIB and may be applied to a variety of lung diseases.

OBJECTIVE: The aim of this pilot study was to determine the combined effect of vitamin D and omega-3 polyunsaturated fatty acid (PUFA) supplementation on airway function and inflammation in recreational athletes with exercise-induced bronchoconstriction (EIB).
METHODS: Ten recreational athletes with EIB participated in a single-blind, placebo-controlled trial over six consecutive weeks. All subjects attended the laboratory on three occasions. Each visit was separated by a period of 3 weeks: visit 1 (usual diet), visit 2 (placebo) and visit 3 (SMARTFISH® NutriFriend 2000; 30 µg vitamin D3-3000 mg eicosapentaenoic acid, 3000 mg docosahexaenoic acid) consumed once daily for a period of 3 weeks. Venous blood was collected at the beginning of each trial to determine vitamin D status. Spirometry was performed pre- and post-eucapnic voluntary hyperpnoea (EVH).
RESULTS: The Maximum fall in FEV1 (ΔFEV1max) post-EVH was not different between visits (usual diet: -15.9 ± 3.6%, placebo: -16.1 ± 6.1%, vitamin D + omega-3 PUFA: -17.8 ± 7.2%). Serum vitamin D remained unchanged between visits.
CONCLUSIONS: Vitamin D and omega-3 PUFA supplementation does not attenuate the reduction in lung function post-EVH. This finding should be viewed as preliminary until the results of randomised controlled trials are made available.

OBJECTIVE: The pathogenesis of exercise-induced bronchoconstriction (EIB) in asthma is incompletely understood. The role of exhaled breath condensate (EBC) annexin A5, which is an anti-inflammatory mediator, has not been investigated. The purpose of this study is to evaluate EBC annexin A5 levels in EIB in asthmatic children.
METHODS: Two groups of children were enrolled in this study: asthmatic children with positive (n=11) and negative (n=7) responses to exercise. The levels of pre- and post-exercise EBC annexin A5 were determined with using enzyme-linked immunosorbent assay (ELISA).
RESULTS: We observed significant higher pre-exercise EBC annexin A5 levels in the challenge test negative children than in the challenge test positive children (p<0.05). No significant difference was observed in the post-exercise EBC annexin A5 levels between the groups (p>0.05). Also, no significant difference was observed between pre- and post-exercise EBC annexin A5 levels within each group (p>0.05). There was an inverse correlation between annexin A5 levels and a reduction in forced expiratory volume at one second percent (FEV1%) (p=0.009, r=-0.598).
CONCLUSIONS: Our preliminary study showed that EBC annexin A5 may have a possible preventive role in EIB in asthma. Annexin A5 and related compounds may provide novel therapeutic approaches to the treatment of EIB in asthma.

BACKGROUND: To determine the effects of montelukast added to maintenance inhaled steroids (ICS) therapy during the school year in children with stable asthma on the ICS use, frequency of exacerbations, lung function, asthma symptoms, fractional exhaled nitric oxide (FeNO) level and exercise-induced bronchoconstriction (EIB).
METHODS: Seventy six asthmatic children aged 6-14 years, allergic to house dust mites were randomized to a double-blinded trial comparing montelukast therapy to a matching placebo. We studied following end-points: the reduction in the ICS dose, the frequency of exacerbations, lung function, asthma control test score, and the change from baseline in FEV1 during a standardized exercise treadmill challenge. ICS dose was adjusted in a stepwise fashion to determine the lowest dose necessary to control asthma symptoms.
RESULTS: We showed that children with baseline value of FeNO above 31 ppb and well controlled asthma symptoms on low doses of ICS, benefit the most from additive therapy with montelukast; their cumulative ICS dose is lower than in children treated with ICS only. Also, the addition of montelukast to regular treatment in asthmatic children resulted in a significant reduction in the frequency of exacerbations and EIB protection.
CONCLUSIONS: It is reasonable to add montelukast to ICS therapy in asthmatic children during the school year, to lower cumulative ICS dose in children with well controlled asthma symptoms, as well as to reduce number of exacerbations, and to achieve better control of EIB.
BACKGROUND: NCT01266772.