Eight-week supplementation of Aronia berry extract promoted the glutathione defence system against acute aerobic exercise-induced oxidative load immediately and 30 min post-exercise in healthy adults: a double-blind, randomised controlled trial.

BACKGROUND: Food antioxidants have received prompt attention for controlling oxidative stress encountered in daily life. This study aimed to examine the protective effects of Aronia berry extract (ABE) supplementation on acute aerobic exercise (AAE)-induced oxidative stress in healthy subjects. METHODS: We assessed a battery of antioxidant defence and oxidative stress parameters at pre-exercise, immediately post-exercise and 30 min post-exercise in healthy middle-aged adults with habitually low intakes of fruit and vegetables in an 8-week, double-blind, randomised, controlled clinical trial with two arms (n = 70). The AAE challenge model, characterised as a treadmill exercise for 30 min at 60% VO2 maximum, was applied to load oxidative stress at the end of the study. Pearson's correlation analysis assessed the association between the changes in antioxidant defence capacities and oxidative stress levels. RESULTS: The time-course-dependent oxidative stress was well observed in the placebo group regarding the glutathione peroxidase (GPx) activity and the reduced glutathione (GSH) availability for antioxidant defence and erythrocyte malondialdehyde, interleukin-6 and lactate levels for oxidative damage. Meanwhile, the ABE supplementation effectively strengthened the glutathione defence system by increasing GSH availability and GPx activity immediately post-exercise and 30 min post-exercise. In addition, the scatter plot and linear regression analysis revealed strong negative correlations of GSH availability with oxidised low-density lipoprotein and plasma malonaldehyde levels. CONCLUSION: These findings suggest that daily supplementation of 300 mg ABE might help boost GSH levels and an adaptive antioxidant enzyme defence system of erythrocytes in healthy adults with habitually low fruit and vegetable intakes.

The Use of Exercise Challenge Testing and Fractional Exhaled Nitric Oxide in Diagnosis of Chest Tightness Variant Asthma in Children.

BACKGROUND: Chest tightness variant asthma (CTVA) in children presents with chest tightness as the sole manifestation. Diagnostic tests are needed given the lack of typical asthma symptoms. The present study aimed to investigate the diagnostic value of exercise challenge testing (ECT) and fractional exhaled nitric oxide (FeNO) in pediatric CTVA. METHODS: We included 98 children aged 6-13 years with chest tightness as the sole symptom for >4 weeks. All subjects underwent FeNO measurement, spirometry and ECT, and received 4-week budesonide/formoterol treatment. According to treatment responses, children were categorized into CTVA (n = 12) and non-CTVA (n = 86) groups. Differences in clinical characteristics and FeNO, spirometry, and ECT results were compared between the two groups. The FeNO and ECT diagnostic performances were determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Children with CTVA exhibited significantly higher Mycoplasma pneumoniae IgG, total IgE, and FeNO values; greater post-ECT forced expiratory volume in 1 s (FEV1) fall; and more frequent sensitization to mites and pets than those without CTVA. Further logistic regression revealed that higher FEV1 fall (OR, 1.39; 95% CI: 1.11-1.74; p = 0.004) and higher FeNO values (OR, 1.04; 95% CI: 1.01-1.08; p = 0.014) were risk factors associated with CTVA. FEV1 fall and FeNO had similar areas under the ROC curve (AUCs) (0.79 vs. 0.78; p = 0.924), and their optimal CTVA-prediction cutoff values were 9.9% and 15.0 ppb, respectively. The AUC of FEV1 fall and FeNO combination was higher at 0.86 (95% CI: 0.78-0.93); however, no difference was observed using the single test (p > 0.05). Their combination exhibited a relatively higher sensitivity than that of FEV1 fall alone (0.75 vs. 0.67) and higher positive predictive value than that of FeNO alone (0.60 vs. 0.29). CONCLUSION: CTVA is a cause of unexplained recurrent chest tightness in children. FeNO ≥15.0 ppb and post-ECT FEV1 fall ≥9.9% are diagnostically valuable for CTVA in children, with their combination potentially contributing to greater diagnostic accuracy.

Can the response to a single dose of beclomethasone dipropionate predict the outcome of long-term treatment in childhood exercise-induced bronchoconstriction?

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is a frequent and highly specific symptom of childhood asthma. Inhaled corticosteroids (ICS) are the mainstay of controller therapy for EIB and asthma; however, a proportion of asthmatic children and adolescents is less responsive to ICS. We hypothesized that a single dose response to ICS could function as a predictor for individual long-term efficacy of ICS. OBJECTIVE: To assess the predictive value of the bronchoprotective effect of a single-dose beclomethasone dipropionate (BDP) against EIB for the bronchoprotective effect of 4 weeks of treatment, using an exercise challenge test (ECT). METHODS: Thirty-two steroid-naïve children and adolescents aged 6 to 18 years with EIB were included in this prospective cohort study. They performed an ECT at baseline, after a single-dose BDP (200µg) and after 4 weeks of BDP treatment (100 µg twice daily) to assess EIB severity. RESULTS: The response to a single-dose BDP on exercise-induced fall in FEV1 showed a significant correlation with the response on exercise-induced fall in FEV1 after 4 weeks of BDP treatment (r = .38, p = .004). A reduction in post-exercise fall in FEV1 of more than 8% after a single-dose BDP could predict BDP efficacy against EIB after 4 weeks of treatment with a positive predictive value of 100% (CI: 86.1-100%) and a negative predictive value of 29.4% (CI: 11.7%-53.7%). CONCLUSION: We found that the individual response to a single-dose BDP against EIB has a predictive value for the efficacy of long-term treatment with BDP. This could support clinicians in providing personalized management of EIB in childhood asthma.

Fluticasone furoate/vilanterol versus fluticasone propionate in patients with asthma and exercise-induced bronchoconstriction.

Objective: To investigate whether once-daily (OD) fluticasone furoate (FF)/vilanterol (VI) provides greater long-term protection from postexercise fall in forced expiratory volume in 1 s (FEV1) than twice-daily (BD) fluticasone propionate (FP) in patients with asthma and exercise-induced bronchoconstriction. Methods: A randomized, double-blind, crossover study was conducted in patients (aged 12-50 years) on low-/mid-dose maintenance inhaled corticosteroid. Following a 4-week run-in period (FP 250 µg BD), patients with a ≥ 20% decrease in postexercise FEV1 received FF/VI 100/25 µg OD or FP 250 µg BD for 2 weeks. Exercise challenges were carried out 23 h after the first dose of study medication, and 12 and 23 h after evening clinic dose at the end of the 2-week treatment period. After a 2-week washout period (FP 250 µg), patients crossed over treatments, with procedures and tests repeated. The primary endpoint was mean maximal percentage decrease from pre-exercise FEV1 following exercise challenge 12-h postevening dose on Day 14. Results: The mean maximal percentage decrease from pre-exercise FEV1 after the 12-h exercise challenge (Day 14) was 15.02% with FF/VI, and 16.71% with FP (difference, -1.69; 95% confidence interval, -3.76 to 0.39; p = 0.109). After the 23-h exercise challenge (Day 14), respective mean maximal decreases were 11.90% and 14.05% (difference, -2.15; 95% confidence interval, -4.31 to 0.01). Conclusion: The study failed to show a difference between FF/VI and FP at providing long-term protection from exercise-induced bronchoconstriction.

Oil supplementation with a special combination of n-3 and n-6 long-chain polyunsaturated fatty acids does not protect for exercise induced asthma: a double-blind placebo-controlled trial.

BACKGROUND: Many patients suffering from exercise-induced asthma (EIA) have normal lung function at rest and show symptoms and a decline in FEV1 when they do sports or during exercise-challenge. It has been described that long-chain polyunsaturated fatty acids (LCPUFA) could exert a protective effect on EIA. METHODS: In this study the protective effect of supplementation with a special combination of n-3 and n-6 LCPUFA (sc-LCPUFA) (total 1.19 g/ day) were investigated in an EIA cold air provocation model. PRIMARY OUTCOME MEASURE: Decrease in FEV1 after exercise challenge and secondary outcome measure: anti-inflammatory effects monitored by exhaled NO (eNO) before and after sc-LCPUFA supplementation versus placebo. RESULTS: Ninety-nine patients with exercise-induced symptoms aged 10 to 45 were screened by a standardized exercise challenge in a cold air chamber at 4 °C. Seventy-three patients fulfilled the inclusion criteria of a FEV1 decrease > 15% and were treated double-blind placebo-controlled for 4 weeks either with sc-LCPUFA or placebo. Thirty-two patients in each group completed the study. Mean FEV1 decrease after cold air exercise challenge and eNO were unchanged after 4 weeks sc-LCPUFA supplementation. CONCLUSION: Supplementation with sc-LCPUFA at a dose of 1.19 g/d did not have any broncho-protective and anti-inflammatory effects on EIA. TRIAL REGISTRATION: Clinical trial registration number: NCT02410096. Registered 7 February 2015 at Clinicaltrial.gov.

Predictors and reproducibility of exercise-induced bronchoconstriction in cold air.

BACKGROUND: Physical activity is an important part of life, and hence exercise-induced bronchoconstriction (EIB) can reduce the quality of life. A standardized test is needed to diagnose EIB. The American Thoracic Society (ATS) guidelines recommend an exercise challenge in combination with dry air. We investigated the feasibility of a new, ATS guidelines conform exercise challenge in a cold chamber (ECC) to detect EIB. The aim of this study was to investigate the surrogate marker reaction to methacholine, ECC and exercise challenge in ambient temperature for the prediction of a positive reaction and to re-evaluate the reproducibility of the response to an ECC. METHODS: Seventy-eight subjects aged 6 to 40 years with suspected EIB were recruited for the study. The subjects performed one methacholine challenge, two ECCs, and one exercise challenge at an ambient temperature. To define the sensitivity and specificity of the predictor, a receiver-operating characteristic curve was plotted. The repeatability was evaluated using the method described by Bland and Altman (95% Limits of agreement). RESULTS: The following cut-off values showed the best combination of sensitivity and specificity: the provocation dose causing a 20% decrease in the forced expiratory volume in 1 s (PD20FEV1) of methacholine: 1.36 mg (AUC 0.69, p < 0.05), the maximal decrease in FEV1 during the ECC: 8.5% (AUC 0.78, p < 0.001) and exercise challenges at ambient temperatures: FEV1 5.2% (AUC 0.64, p = 0.13). The median decline in FEV1 was 14.5% (0.0-64.2) during the first ECC and 10.7% (0.0-52.5) during the second ECC. In the comparison of both ECCs, the Spearman rank correlation of the FEV1 decrease was r = 0.58 (p < 0.001). The 95% limits of agreement (95% LOAs) for the FEV1 decrease were - 17.7 to 26.4%. CONCLUSIONS: The surrogate markers PD20FEV1 of methacholine and maximal decrease in FEV1 during ECC can predict a positive reaction in another ECC, whereas the maximal FEV1 decrease in an exercise challenge at an ambient temperature was not predictive. Compared with previous studies, we can achieve a similar reproducibility with an ECC. CLINICAL TRIAL REGISTRATION: NCT02026492 (retrospectively registered 03/Jan/2014).

Exhaled NO as a predictor of exercise-induced asthma in cold air.

PURPOSE: Physical activity is an important part of life, and exercise-induced asthma (EIA) can reduce the quality of life. A standardized exercise challenge is needed to diagnose EIA, but this is a time consuming, effortful and expensive method. Exhaled nitric oxide (eNO) as a marker of eosinophil inflammation is determined rapidly and easily. The aim of this study was to investigate eNO as surrogate marker for predicting a positive reaction in an exercise challenge in a cold chamber (ECC). METHODS: A total of 143 subjects aged 6-45 years with suspected EIA were recruited for the study. The subjects underwent an eNO measurement, an ECC and a skin prick test (SPT). To define the sensitivity and specificity of eNO as predictor, a receiver-operating characteristic (ROC) curve was plotted. The individual probability of the occurrence of a positive reaction after ECC based on an eNO value was calculated using a logistic regression model. RESULTS: An eNO cut-off value of 18.5 ppb (area under the curve (AUC) 0.71, p < 0.001) showed the best combination of sensitivity and specificity for a positive reaction (forced expiratory volume in 1 s (FEV1) decrease ≥ 10% after ECC) for the whole group. An eNO cut-off value of 46.0 ppb had a specificity of 100.0% to predict a significant FEV1 decrease and may save exercise testing in 22.4% of patients. A negative predictive level with a high sensitivity and negative predictive value (NPV) could not be defined. In the subgroup that was house dust might (HDM) allergy positive (HDM pos; n = 68, 45.5% of all subjects), an eNO cut-off value of 35.5 ppb (AUC 0.79, p < 0.01) showed the best combination of sensitivity and specificity for a positive reaction after the ECC with a specificity 100.0% and may save exercise testing in 45.6% of HDM pos patients. Using logistic regression, a 95% probability for a positive FEV1 decrease after ECC was estimated at 53 ppb for the whole group and at 47 ppb for the HDM pos subgroup. CONCLUSIONS: Exhaled NO measurement is a screening tool for EIA, especially in HDM pos subjects. In a real-life setting, a cut-off value of 46.0 ppb detects EIA at 100% in all suspected patients, and a cut-off level of 35.5 ppb is valuable marker of EIA in patients with an HDM allergy. These levels can save time and costs in a large proportion of patients and will be helpful for clinicians.

Exhaled nitric oxide and other exhaled biomarkers in bronchial challenge with exercise in asthmatic children: current knowledge.

The fractional concentration of exhaled nitric oxide (FENO), a known marker of atopic-eosinophilic inflammation, may be used as a surrogate to assess exercise-induced bronchoconstriction (EIB) in asthmatic children. The predictive value of baseline FENO for EIB appears to be influenced by several factors, including age, atopy, current therapy with corticosteroids and measurement technique. Nonetheless, FENO cut-off values appear to be able to rule out EIB. FENO levels decrease during EIB, apparently through neural mechanisms rather than by decreased airway-epithelial surface. Partition of FENO into proximal and peripheral contributions of the respiratory tract may improve our understanding on NO exchange during exercise and help to screen subjects prone to EIB. Other biomarkers of inflammation and oxidative stress contained in exhaled gases and exhaled breath condensate (EBC) may shed light on the pathophysiology of EIB. Exhaled breath temperature is a promising real-time measurement whose routine use for assessing EIB warrants further investigation.

Methacholine challenge is insufficient to exclude bronchial hyper-responsiveness in a symptomatic military population.

BACKGROUND: Bronchial hyper-responsiveness in a military population has been evaluated by direct and indirect challenge methods. We hypothesized that negative methacholine challenge testing (MCT) was not sufficient to exclude significant bronchial hyper-responsiveness in a symptomatic military population with exertional dyspnea. The purpose of our study was to identify bronchial hyper-responsiveness in symptomatic military recruits and active duty personnel with normal baseline spirometry and negative pharmacologic bronchoprovocation testing. METHODS: We performed a retrospective single center electronic chart review of symptomatic service members with a negative MCT who completed a subsequent exercise challenge test (ECT). RESULTS: ECT was positive in 45 (26.4%) of 171 subjects (98 recruits). Subjects with a positive ECT had lower baseline forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC than those with a negative ECT, and these differences were statistically significant. The mean drop in FEV1 with exercise challenge positive patients was 17.9 ± 9.2%, and the mean drop in FEV1 with MCT was significantly greater in exercise challenge positive patients (-9.5 ± 5.5 vs. -7.6 ± 5.5, p = 0.042). Exercise-induced bronchoconstriction (EIB) was observed in 41% of all recruits who subsequently did not complete training. Only 1 recruit subject of 28 with EIB completed training. CONCLUSIONS: Methacholine challenge is an insufficient screening test to detect bronchial hyper-responsiveness in a symptomatic military population. In military recruits, EIB is associated with training failure.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.

The effect of nose clip on exercise-induced bronchoconstriction in adolescents.

BACKGROUND: Oral breathing is considered to increase hyper-responsiveness of the airways. Data on the need for nose clip (NC) during exercise challenge test (ECT) in children and adolescents is scarce. Ouraim was to evaluate the role of NC during ECT in children and adolescents. METHODS: A prospective, cohort study; children referred for ECT were evaluated on two separate visits, with and without a NC. Demographic, clinical data and measurements of lung functions were recorded. Allergy and asthma control were evaluated by Total Nasal Symptoms Score (TNSS) and Asthma Control Test (ACT) questionnaires. RESULTS: Sixty children and adolescents (mean age 16.7 ± 1.1 years, 38% Female,) performed ECT with NC and 48 (80%) completed visit 2 (ECT without NC), 8.7 ± 7.9 days after visit 1. Following exercise, 29/48 patients (60.4%) with NC had a decline of ≥12% in forced expiratory volume in the first second (FEV1 ) (positive ECT) compared to only 16/48 (33.3%) positive tests without NC (p = 0.0008). Test result was changed in 14 patients from positive ECT (with NC) to negative ECT (no NC) and in only one patient from negative to positive. The use of NC resulted in greater FEV1 decline (median 16.3% predicted, IQR 6.0-19.1% predicted vs. median 4.5% predicted, IQR 1.6-18.4% predicted, p = 0.0001), and better FEV1 increase after bronchodil at or inhalation compared to ECT without NC. Higher TNSS scores did not predict higher probability to positive ECT. CONCLUSIONS: The use of NC during ECT increases detection rate of exercise induced bronchoconstriction during ECT in the pediatric population. These findings strengthen the recommendation of nasal blockage during ECT in children and adolescents.

Association of childhood asthma with Gasdermin B (GSDMB) and Oromucoid-like 3 (ORMDL3) genes.

OBJECTIVE: Genome-length association studies have shown that Gasdermin B (GSDMB) and Orosomucoid-like 3 (ORMDL3) genes located on the long arm of chromosome 17 are associated with asthma. In this study, it was aimed to determine the possible relationship between asthma control test (ACT), exercise provocation test (ECT), and fractional nitric oxide (FENO) levels and GSDMB and ORMDL3 gene expressions. METHODS: 59 asthmatic and 38 non-asthmatic children were included in the study. We divided the patient group into two subgroups as mild persistent asthma (29 patients) and moderate persistent asthma (30 patients). ORMDL3, GSDMB gene expression levels, ECT, total IgE levels, and eosinophil counts were measured in all cases. In addition, ACT and FeNO levels were measured in children with asthma. Afterward, the relationship of ORMDL3 and GSDMB gene expression coefficient changes with ECT, ACT, and FeNO was examined. RESULTS: When patients with ACT ≤15 were compared with patients with ACT ≥20, ORMDL3 and GSDMB gene expressions were increased 6.74 and 11.74 times, respectively. Comparing patients with ACT ≥20 and ACT ≤15 in terms of coefficient changes (ΔCq), higher change values were observed for ΔCq ORMDL3 in patients with ACT ≤15 (p=0.015). Similarly, when patients with FENO ≤25 ppb were compared with patients with FENO >25 ppb, ORMDL3 and GSDMB gene expressions were increased by 2.93 and 3.56 times, respectively. When the coefficient changes were compared, no significant difference was found between FENO≤25 and FENO >25 patients. There was a slight negative correlation between ΔCq values and ACT score (p=0.003, r=-0.418 for ORMDL3, and p=0.016, r=-0.345 for GSDMB). In addition, we observed a statistically significant positive correlation between ORMDL3 and GSDMB gene expressions (r=0.80, p<0.001). CONCLUSION: We showed that increased ORMDL3 and GSDMB gene expression levels may be associated with ACT scores, FeNO and ECT in asthma. These findings may encourage future studies with larger numbers of subjects that can use gene expression levels in various asthma phenotypes for prognostic prediction.

Unsupervised field-based exercise challenge tests to support the detection of exercise-induced lower airway dysfunction in athletes.

Background: Athletes are at risk for developing exercise-induced lower airway narrowing. The diagnostic assessment of such lower airway dysfunction (LAD) requires an objective bronchial provocation test (BPT). Objectives: Our primary aim was to assess if unsupervised field-based exercise challenge tests (ECTs) could confirm LAD by using app-based spirometry. We also aimed to evaluate the diagnostic test performance of field-based and sport-specific ECTs, compared with established eucapnic voluntary hyperpnoea (EVH) and methacholine BPT. Methods: In athletes with LAD symptoms, sensitivity and specificity analyses were performed to compare outcomes of (1) standardised field-based 8 min ECT at 85% maximal heart rate with forced expiratory volume in 1 s (FEV1) measured prechallenge and 1 min, 3 min, 5 min, 10 min, 15 min and 30 min postchallenge, (2) unstandardised field-based sport-specific ECT with FEV1 measured prechallenge and within 10 min postchallenge, (3) EVH and (4) methacholine BPT. Results: Of 60 athletes (median age 17.5; range 16-28 years.; 40% females), 67% performed winter-sports, 43% reported asthma diagnosis. At least one positive BPT was observed in 68% (n=41/60), with rates of 51% (n=21/41) for standardised ECT, 49% (n=20/41) for unstandardised ECT, 32% (n=13/41) for EVH and methacholine BPT, while both standardised and unstandardised ECTs were simultaneously positive in only 20% (n=7/35). Standardised and unstandardised ECTs confirmed LAD with 54% sensitivity and 70% specificity, and 46% sensitivity and 68% specificity, respectively, using EVH as a reference, while EVH and methacholine BPT were both 33% sensitive and 85% specific, using standardised ECTs as reference. Conclusion: App-based spirometry for unsupervised field-based ECTs may support the diagnostic process in athletes with LAD symptoms. Trial registration number: NCT04275648.

Exercise-Induced Urticaria: A Rare Case Report.

Exercise is an important part of a healthy lifestyle. However, there is a subset of the population who are allergic to exercise. Exercise-induced urticaria is a rare clinical condition, which, as the name suggests, manifests as flushing, pruritus, and hives following physical exercise. A minority of patients even develop more severe reactions including angioedema and anaphylaxis induced by exercise. Some patients are affected by certain cofactors that constitute food-dependent exercise-induced urticaria, which is relatively more common when compared to exercise-induced urticaria without other cofactors. This case report documents a healthy 27-year-old Asian male, with no other allergies or cofactors, who was diagnosed with exercise-induced urticaria. He was diagnosed based on history and a positive exercise challenge test. Avoidance of exercise is the mainstay of prophylactic treatment for this condition. Modification of physical activity proved to be effective for treating this patient. We intend to increase awareness about this rare condition through this case report and literature review.

The effect of stress on the transcriptomes of circulating immune cells in patients with Gulf War Illness.

AIMS: In an effort to gain further insight into the underlying mechanisms tied to disease onset and progression of Gulf War Illness (GWI), our team evaluated GWI patient response to stress utilizing RNA-Seq. MAIN METHODS: The protocol included blood collection before exercise challenge (baseline), at maximal exertion, and after exercise challenge (recovery - four hours post-exercise challenge). Peripheral blood mononuclear cell (PBMC) transcriptomics data were analyzed to understand why GWI patients process stressors differently from their healthy counterparts. KEY FINDINGS: Our findings validate previously identified dysregulation of immune and inflammatory pathways among GWI patients as well as highlight novel immune and inflammatory markers of disease activity. These results provide a foundation for future research efforts in understanding GWI pathophysiology and creating targeted treatments. SIGNIFICANCE: Gulf War Illness is a complex, chronic, and debilitating multi-system illness impacting 25%-30% of the U.S. troops deployed to the 1990-1991 Gulf War. The condition is characterized by medically unexplained fatigue and affects multiple organ systems. Because the underlying mechanisms are largely unknown, patients receive symptom-based treatment, rather than targeting fundamental biological processes. To the best of our knowledge, this is the first study that applies RNA-Seq to analyze the effect of GWI, and the response to stressors in GWI, on the transcriptomic changes in circulating immune cells.

Short- and long-term effects of fluticasone furoate/vilanterol in exercising asthmatic adolescents: A randomized and open label trial.

PURPOSE: 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.

Does exercise-induced bronchoconstriction affect physical activity patterns in asthmatic children?

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.

Correlation of spirometry and body plethysmography during exercise-induced bronchial obstruction.

BACKGROUND: The exercise challenge is the gold standard for diagnosing exercise-induced bronchoconstriction (EIB). Airway obstructions appear up to 30 min after the challenge, with a maximum decrease in spirometry and a maximum increase in airway resistance. There is evidence that changes in body plethysmography parameters are more sensitive to the exercise challenge and precede those in spirometry. PURPOSE: To compare changes in body plethysmography and spirometry parameters after exercise challenges and to verify the cut-off values of sReff in EIB. PROCEDURES: In 82 subjects with suspected EIB, a total of 473 lung function tests were measured at baseline and at 5, 10, 15, and 30 min after exercise challenges at different stages of bronchial obstruction. FINDINGS: The maximum changes in the body plethysmography parameter sReff significantly preceded the maximum changes in the spirometry parameter FEV1 (sReff: 12.2 min ±8.8, FEV1: 15.2 min ±9.3, p < 0.005). The parameters of sReff and FEV1 had a strong negative correlation (r = -0.63, p < 0.0001) with a nonlinear, polynomial relationship. Furthermore, sReff and Reff had a strong linear correlation (r = 0.86, p < 0.001), and Reff and Rtot had a perfect linear correlation (r = 0.99, p < 0.001). Based on baseline values and on quantile regression, an increase of 0.25 kPa s in sReff was defined as significant. Using this cut-off value, FEV1 and sReff almost equally detected EIB. CONCLUSION: The changes in sReff were more sensitive and better indicated lung impairment than did the changes in FEV1, which underestimated the degree of hyperinflation.

Efficacy and Safety of Omalizumab (Xolair) for Cholinergic Urticaria in Patients Unresponsive to a Double Dose of Antihistamines: A Randomized Mixed Double-Blind and Open-Label Placebo-Controlled Clinical Trial.

BACKGROUND: Cholinergic urticaria (UCOL) is a highly disabling inducible urticaria triggered by an increase in core body temperature. OBJECTIVE: To explore the safety and efficacy of omalizumab in controlling UCOL. METHODS: We conducted a multicenter randomized mixed double-blind and open-label (first 4 months blinded followed by 8 months open-label) placebo-controlled clinical trial in 22 patients suffering from UCOL who were unresponsive to a double dose of antihistamines. We performed an exercise challenge test during each visit as our main outcome variable. RESULTS: The overall rate of exercise challenge test negative at week 48 was 31.3%, with an average increase in exercise challenge test negative rate of 2.9% points (95% CI, 1.5-4.2) per visit. Statistically significant differences in the negative exercise challenge test rate between the placebo and active intervention groups were not observed during the blinded period (first 4 months of the study). However, from the fourth dose, a progressive improvement was observed. When comparing before and after treatment, statistically significant improvements in all secondary outcome measures were noted after 4 doses (UCOL score: P = .0015; visual analog scale score: P = .0108; days with symptoms: P = .0125) and after 8 doses (UCOL score: P = .0005; chronic urticaria quality of life questionnaire: P = .0105; visual analog scale score: P = .0008; and days with symptoms: P = .0144). In the follow-up visit after the cessation of treatment, the symptoms reappeared, with positive exercise challenge test result and significant increases in all variables. Only 4 of 22 patients remained asymptomatic after 3 months of no treatment. No adverse effects were reported. CONCLUSIONS: This randomized mixed double-blind and open-label placebo-controlled trial showed evidence of the safety and potential efficacy of omalizumab in patients with UCOL.

Exercise-induced bronchoconstriction in children with asthma: An observational cohort study.

BACKGROUND/PURPOSE: 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). CONCLUSION: 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.