Inflammatory basis of exercise-induced bronchoconstriction.
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ABSTRACT: Rationale
Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition with unclear pathogenesis. Two competing theories of the pathogenesis of EIB differ regarding the inflammatory basis of this condition.Objectives
Our goals were to establish whether epithelial cell and mast cell activation with release of inflammatory mediators occurs during EIB and how histamine and cysteinyl leukotriene antagonists alter the airway events occurring during EIB.Methods
Induced sputum was used to measure mast cell mediators and eicosanoids at baseline and 30 minutes after exercise challenge in 25 individuals with asthma with EIB. In a randomized, double-blind crossover study, the cysteinyl leukotriene antagonist montelukast and antihistamine loratadine or two matched placebos were administered for two doses before exercise challenge.Main results
The percentage of columnar epithelial cells in induced sputum at baseline was associated with the severity of EIB. After exercise challenge, histamine, tryptase, and cysteinyl leukotrienes significantly increased and prostaglandin E(2) and thromboxane B(2) significantly decreased in the airways, and there was an increase in columnar epithelial cells in the airways. The concentration of columnar epithelial cells was associated with the levels of histamine and cysteinyl leukotrienes in the airways. Treatment with montelukast and loratadine inhibited the release of cysteinyl leukotrienes and histamine into the airways, but did not inhibit the release of columnar epithelial cells into the airways.Conclusions
These data indicate that epithelial cells, mast cell mediators, and eicosanoids are released into the airways during EIB, supporting an inflammatory basis for EIB.
SUBMITTER: Hallstrand TS
PROVIDER: S-EPMC2041799 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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??V (1.82-7.84), compared to children without EIB; 0.20??V (-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??V (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.
| S-EPMC7322899 | biostudies-literature
Project description: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.
| S-EPMC6989467 | biostudies-literature
Project description:Whole-body warm-up exercises were shown to attenuate exercise-induced bronchoconstriction (EIB). Whether intense pre-exercise hyperpnea offers similar protection and whether this might negatively affect exercise performance is unknown. Nine subjects with EIB (25±5 yrs; forced expiratory volume in 1s [FEV1], 104±15% predicted) performed an exercise challenge (ECh) followed-after 30min-by a constant-load cycling test to exhaustion. The ECh was preceded by one of four conditions: by i) control warm-up (CON) or by 10min of normocapnic hyperpnea with partial rebreathing at either ii) 50% (WU50) or iii) variable intensity (8x 30s-80%/45s-30%; WU80/30), or at iv) 70% (WU70) of maximal voluntary ventilation. FEV1 was measured at baseline and in 5-min intervals until 15min after CON/warm-up and 30min after ECh. None of the warm-up conditions induced EIB. The maximal post-ECh decrease in FEV1 was -13.8±3.1% after CON, -9.3±5.0% after WU50 (p = 0.081 vs. CON), -8.6±7.5% after WU80/30 (p = 0.081 vs. CON) and -7.2±5.0% after WU70 (p = 0.006 vs. CON), and perception of respiratory exertion was significantly attenuated (all p?0.048), with no difference between warm-up conditions. Only after CON, FEV1 remained significantly reduced up to the start of the cycling endurance test (-8.0±4.3%, p = 0.004). Cycling performance did not differ significantly between test days (CON: 13±7min; WU50: 14±9min; WU80/30: 13±9min; WU70: 14±7min; p = 0.582). These data indicate that intense hyperpnea warm-up is effective in attenuating EIB severity and accelerating lung function recovery while none of the warm-up condition do compromise cycling performance.
| S-EPMC5127560 | biostudies-literature
Project description:ObjectiveTo determine whether vitamin C administration influences exercise-induced bronchoconstriction (EIB).DesignSystematic review and meta-analysis.MethodsMEDLINE and Scopus were searched for placebo-controlled trials on vitamin C and EIB. The primary measures of vitamin C effect used in this study were: (1) the arithmetic difference and (2) the relative effect in the postexercise forced expiratory volume in 1 s (FEV1) decline between the vitamin C and placebo periods. The relative effect of vitamin C administration on FEV1 was analysed by using linear modelling for two studies that reported full or partial individual-level data. The arithmetic differences and the relative effects were pooled by the inverse variance method. A secondary measure of the vitamin C effect was the difference in the proportion of participants suffering from EIB on the vitamin C and placebo days.Results3 placebo-controlled trials that studied the effect of vitamin C on EIB were identified. In all, they had 40 participants. The pooled effect estimate indicated a reduction of 8.4 percentage points (95% CI 4.6 to 12) in the postexercise FEV1 decline when vitamin C was administered before exercise. The pooled relative effect estimate indicated a 48% reduction (95% CI 33% to 64%) in the postexercise FEV1 decline when vitamin C was administered before exercise. One study needed imputations to include it in the meta-analyses, but it also reported that vitamin C decreased the proportion of participants who suffered from EIB by 50 percentage points (95% CI 23 to 68); this comparison did not need data imputations.ConclusionsGiven the safety and low cost of vitamin C, and the positive findings for vitamin C administration in the three EIB studies, it seems reasonable for physically active people to test vitamin C when they have respiratory symptoms such as cough associated with exercise. Further research on the effects of vitamin C on EIB is warranted.
| S-EPMC3686214 | biostudies-literature
Project description:BackgroundPhysical 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.MethodsSeventy-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).ResultsThe 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%.ConclusionsThe 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 registrationNCT02026492 (retrospectively registered 03/Jan/2014).
| S-EPMC6524332 | biostudies-literature
Project description: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.
| S-EPMC6498950 | biostudies-literature
Project description:Asthma is a heterogeneous disease. Exercise-induced bronchoconstriction (EIB) is a distinct syndrome that occurs in 30-50% of asthmatics and is characterized by high levels of pro-inflammatory eicosanoids. We identified genes differentially expressed in the airways of asthmatics with EIB relative to asthmatics without EIB. Genes related to epithelial repair and mast cell infiltration including beta-tryptase and carboxypeptidase A3 were upregulated by exercise challenge in the asthma group with EIB. We confirmed that two novel mediators trefoil factor 3 (TFF3) and transglutaminase 2 (TGM2) have increased expression in airways cells and secreted product in the airways. In vitro studies indicate that 1) TFF3 induces nitric oxide synthase in airway epithelial cells from asthmatics and 2) TGM2 augments the enzymatic activity of secreted phospholipase A2 (sPLA2) group X, an enzyme recently been implicated in asthma pathogenesis. Since PLA2 serves as the first rate-limiting step leading to eicosanoid generation, these results suggest that TGM2 may be a key initiator of the airway inflammatory cascade in asthma. EIB positive and EIB negative subjects sampled pre- and post-exercise
2010-11-10 | E-GEOD-13785 | biostudies-arrayexpress
Project description:In athletes, a secure diagnos is of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and following an exercise bout is intuitively the optimal means for the diagnosis; however, this approach is recognized as having several key limitations. Accordingly, alternative indirect bronchoprovocation tests have been recommended as surrogate means for obtaining a diagnosis of EIB. Of these tests, it is often argued that the eucapnic voluntary hyperpnea (EVH) challenge represents the 'gold standard'. This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation. We also address the performance of EVH against the other functional and clinical approaches commonly adopted for the diagnosis of EIB. The published evidence supports a key role for EVH in the diagnostic algorithm for EIB testing in athletes. However, its wide sensitivity and specificity and poor repeatability preclude EVH from being termed a 'gold standard' test for EIB.
| S-EPMC4963444 | biostudies-other
Project description:Populations with endemic parasitosis have high levels of IgE but low levels of allergic disease. We investigated the association between infection with the parasite Ascaris allergic sensitization, and exercise-induced bronchospasm (EIB).We sought to investigate the effect of Ascaris infection on bronchial hyperreactivity, skin testing, and specific IgE levels.A cross-sectional prevalence survey was conducted in urban and rural South African children to measure levels of EIB. A sample of children was enrolled in a nested case-control study for further investigation based on response to exercise. Analyses used weighted logistic regression.Geometric mean total IgE levels were higher in Ascaris -infected subjects (infected subjects: 451 IU (95% CI, 356-572) vs uninfected subjects: 344 IU (95% CI, 271-437), P = .04), and high levels of total IgE were positively associated with detection of specific IgE to the aeroallergens tested, but there was no significant association between Ascaris infection and titers of specific IgE. Ascaris infection was associated with a decreased risk of a positive skin test response (odds ratio, 0.63; 95% CI, 0.42-0.94; P = .03) but an increased risk of EIB (odds ratio, 1.62; 95% CI, 1.23-2.11; P = .001).In areas of high parasite endemicity, Ascaris might induce an inflammatory response in the lungs independent of its effect on IgE production. This could explain some of the contradictory findings seen in studies examining the association between geohelminth infection, atopy, and asthma.
| S-EPMC4353837 | biostudies-literature
Project description:Exercise-induced bronchoconstriction (EIB) is a common clinical entity in people with asthma. EIB is characterized by postexercise airway obstruction that results in symptoms such as coughing, dyspnea, wheezing, chest tightness, and increased fatigue. The underlying mechanism of EIB is not completely understood. "Osmotic theory" and "thermal or vascular theory" have been proposed. Initial assessment must include a specific work-up to exclude alternative diagnoses like exercise-induced laryngeal obstruction (EILO), cardiac disease, or physical deconditioning. Detailed medical history and clinical examination must be followed by basal spirometry and exercise challenge test. The standardized treadmill running (TR) test, a controlled and standardized method to assess bronchial response to exercise, is the most adopted exercise challenge test for children aged at least 8 years. In the TR test, the goal is to reach the target heart rate in a short period and maintain it for at least 6 min. The test is then followed by spirometry at specific time points (5, 10, 15, and 30 min after exercise). In addition, bronchoprovocation tests like dry air hyperpnea (exercise and eucapnic voluntary hyperpnea) or osmotic aerosols (inhaled mannitol) can be considered when the diagnosis is uncertain. Treatment options include both pharmacological and behavioral approaches. Considering medications, the use of short-acting beta-agonists (SABA) just before exercise is the commonest option strategy, but daily inhaled corticosteroids (ICS) can also be considered, especially when EIB is not controlled with SABA only or when the patients practice physical activity very often. Among the behavioral approaches, warm-up before exercise, breathing through the nose or face mask, and avoiding polluted environments are all recommended strategies to reduce EIB risk. This review summarizes the latest evidence published over the last 10 years on the pathogenesis, diagnosis using spirometry and indirect bronchoprovocation tests, and treatment strategies, including SABA and ICS, of EIB. A specific focus has been placed on EIB management in young athletes, since this condition can not only prevent them from practicing regular physical activity but also competitive sports.
| S-EPMC11312884 | biostudies-literature