Exercise-induced Bronchoconstriction Severity Research Articles

Exercise-Induced Asthma: Managing Respiratory Issues in Athletes.

Asthma is a complex respiratory condition characterized by chronic airway inflammation and variable expiratory airflow limitation, affecting millions globally. Among athletes, particularly those competing at elite levels, the prevalence of respiratory conditions is notably heightened, varying between 20% and 70% across specific sports. Exercise-induced bronchoconstriction (EIB) is a common issue among athletes, impacting their performance and well-being. The prevalence rates vary based on the sport, training environment, and genetics. Exercise is a known trigger for asthma, but paradoxically, it can also improve pulmonary function and alleviate EIB severity. However, athletes' asthma phenotypes differ, leading to varied responses to medications and challenges in management. The unique aspects in athletes include heightened airway sensitivity, allergen, pollutant exposure, and temperature variations. This review addresses EIB in athletes, focusing on pathogenesis, diagnosis, and treatment. The pathogenesis of EIB involves complex interactions between physiological and environmental factors. Airway dehydration and cooling are key mechanisms, leading to osmotic and thermal theories. Airway inflammation and hyper-responsiveness are common factors. Elite athletes often exhibit distinct inflammatory responses and heightened airway sensitivity, influenced by sport type, training, and environment. Swimming and certain sports pose higher EIB risks, with chlorine exposure in pools being a notable factor. Immune responses, lung function changes, and individual variations contribute to EIB in athletes. Diagnosing EIB in athletes requires objective testing, as baseline lung function tests can yield normal results. Both EIB with asthma (EIBA) and without asthma (EIBwA) must be considered. Exercise and indirect bronchoprovocation tests provide reliable diagnoses. In athletes, exercise tests offer effectiveness in diagnosing EIB. Spirometry and bronchodilation tests are standard approaches, but the diagnostic emphasis is shifting toward provocation tests. Despite its challenges, achieving an optimal diagnosis of EIA constitutes the cornerstone for effective management, leading to improved performance, reduced risk of complications, and enhanced quality of life. The management of EIB in athletes aligns with the general principles for symptom control, prevention, and reducing complications. Non-pharmacological approaches, including trigger avoidance and warming up, are essential. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy in athletes. Short-acting beta agonists (SABA) are discouraged as sole treatments. Leukotriene receptor antagonists (LTRA) and mast cell stabilizing agents (MCSA) are potential options. Optimal management improves the athletes' quality of life and allows them to pursue competitive sports effectively.

High Incidence of Bronchospastic Response to a Stair Climbing Exercise.

BackgroundWhile it is increasingly recognized that exercise-induced bronchoconstriction (EIB) affects a substantial proportion of sport participants, the relation of EIB incidence and severity to the type and intensity of exertion remains under-investigated. The aim of this study was to establish the incidence and severity of EIB during a stair race, a highly demanding all-out effort exercise. We hypothesized that a large proportion of participants would develop EIB to this particular high-intensity competition, and that among the predisposing factors, severity of EIB would depend on the level of exertion.MethodologyIn this study, screening for EIB was conducted during the official competitive race to a 114-m skyscraper held during the late spring in a city center of approximately 0.5 million residents. Healthy active men (n = 26; age = 32.0 ± 7.0 years) volunteering for the study from the field of the race were included. Allergy Questionnaire for Athletes was completed, and responses of expiratory capacity (forced expiratory volume in the first second, FEV1) and blood lactate were measured by portable digital devices.ResultsOn average, FEV1 dropped by 10.5 ± 5.6% after the exercise. In 11 (approximately 42.5%) participants, FEV1 drop was >10%, indicative of clinical EIB. While age, anthropometry, training experience, allergy history, baseline FEV1, and post-exercise lactate did not differ in responders versus non-responders, those with FEV1 decrement of >10% were slower in the race.ConclusionsDue to very high incidence of EIB observed in active men performing a maximal-effort task and negative association of EIB with competitive performance, the condition of these individuals undertaking regular intense exercise deserves more attention.

Exercise-induced alterations in phospholipid hydrolysis, airway surfactant, and eicosanoids and their role in airway hyperresponsiveness in asthma.

The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (n = 18) and bronchoalveolar lavage (BAL) fluid (n = 11) were obtained before and after exercise challenge in asthmatic subjects. Samples were analyzed for phospholipid structure, surfactant function, and levels of eicosanoids and secreted phospholipase A2 group 10 (sPLA2-X). A primary epithelial cell culture model was used to model effects of osmotic stress on sPLA2-X. Exercise challenge resulted in increased surfactant degradation, phospholipase activity, and eicosanoid production in sputum samples of all patients. Subjects with EIB had higher levels of surfactant degradation and phospholipase activity in BAL fluid. Higher basal sputum levels of cysteinyl leukotrienes (CysLTs) and prostaglandin D2 (PGD2) were associated with direct AHR, and both the postexercise and absolute change in CysLTs and PGD2 levels were associated with EIB severity. Surfactant function either was abnormal at baseline or became abnormal after exercise challenge. Baseline levels of sPLA2-X in sputum and the absolute change in amount of sPLA2-X with exercise were positively correlated with EIB severity. Osmotic stress ex vivo resulted in movement of water and release of sPLA2-X to the apical surface. In summary, exercise challenge promotes changes in phospholipid structure and eicosanoid release in asthma, providing two mechanisms that promote bronchoconstriction, particularly in individuals with EIB who have higher basal levels of phospholipid turnover.

Determinants of severe exercise-induced bronchoconstriction in Nigerian children with asthma.

Asthmatics with severe exercise-induced bronchoconstriction (EIB) are at high risk of exacerbations. The purpose of this study was to determine the prevalence, phenotypic, and laboratory determinants of severe EIB in Nigerian children with asthma. Children with controlled asthma (n = 101) underwent characterization and free-running exercise bronchoprovocation at a center in Nigeria. Lung function was measured before, then 5, 10, 15, and 30 minutes after 6 to 8 minutes exercise. Severe EIB was defined as ≥50% decrease in forced expired volume in 1 second (FEV1 ) from preexercise. Serum vitamin D and total antioxidant capacity were measured chromatographically. Factors predicting severe EIB were tested by logistic regression. The sample was enriched in children with corticosteroid-naïve, mild intermittent asthma (71%). Thirteen percent had no EIB, 22% had severe and 65% nonsevere EIB. Children with severe EIB had higher preexercise FVC (105% vs 96%; P = .03) and FEV1 (98% vs 90%; P = .07), greater obesity (13.6% vs 1.3%; P = .02), more allergic rhinitis (AR) (63.6% vs 35.4%; P = .03), but less exposure to household pets (31.8% vs 72.2%; P = .003) compared to children with nonsevere EIB. Significant determinants (odds ratios/confidence intervals) for severe EIB were obesity = 12.3 (1.2-125.1), AR = 3.18 (1.19-8.52), blood eosinophilia = 1.005 (1.001-1.009), and hypovitaminosis D = 0.87 (0.81-0.93). In Nigerian children with asthma, severe EIB is common and associated with remediable comorbidities including type 2 pattern inflammation and vitamin D deficiency.

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.

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.

Assessing Exercise-Induced Bronchoconstriction in Children; The Need for Testing.

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.

Impact of detecting and treating exercise-induced bronchoconstriction in elite footballers.

Our aim was to evaluate the prevalence of exercise-induced bronchoconstriction (EIB) in elite football players and assess subsequent impact of therapy on airway health and exercise performance.97 male professional football players completed an airway health assessment with a eucapnic voluntary hyperpnoea (EVH) challenge to diagnose EIB. Players demonstrating a positive result (EVH+) were prescribed inhaler therapy depending on severity, including inhaled corticosteroids and inhaled short-acting β2-agonists, and underwent repeat assessment after 9 weeks of treatment. Eight players (EVH+ n=3, EVH− n=5) completed a peak oxygen uptake (V′O2peak) test at initial and follow-up assessment.Out of the 97 players, 27 (28%) demonstrated a positive EVH result. Of these, 10 had no prior history (37%) of EIB or asthma. EVH outcome was not predictable by respiratory symptoms. Seven (24%) of the 27 EVH+ players attended follow-up and demonstrated improved post-challenge spirometry (forced expiratory volume in 1 s pre-test −22.9±15.4%, post-test −9.0±1.6%; p=0.018). At follow-up V′O2peak improved by 3.4±2.9 mL·kg−1·min−1 in EVH+ players compared to 0.1±2.3 mL·kg−1·min−1 in EVH− players. Magnitude of inference analysis indicated treatment was possibly beneficial (74%) for exercise capacity.Elite football players have a high EIB prevalence. Treatment with inhaler therapy reduces EIB severity.

BMI predicts exercise induced bronchoconstriction in asthmatic boys.

Exercise induced bronchoconstriction (EIB) is a frustrating morbidity of asthma in children. Obesity has been associated with asthma and with more severe EIB in asthmatic children. To quantify the effect of BMI on the risk of the occurrence of EIB in children with asthma. Data were collected from six studies in which exercise challenge tests were performed according to international guidelines. We included 212 Children aged 7-18 years, with a pediatrician-diagnosed mild-to-moderate asthma. A total of 103 of 212 children (49%) had a positive exercise challenge (fall of FEV1 ≥ 13%). The severity of EIB, as measured by the maximum fall in FEV1 , was significantly greater in overweight and obese children compared to normal weight children (respectively 23.9% vs 17.9%; P = 0.045). Asthmatic children with a BMI z-score around +1 had a 2.9-fold higher risk of the prevalence of EIB compared to children with a BMI z-score around the mean (OR 2.9; 95%CI: 1.3-6.1; P < 0.01). An increase in BMI z-score of 0.1 in boys led to a 1.4-fold increased risk of EIB (OR 1.4; 95%CI: 1.0-1.9; P = 0.03). A reduction in pre-exercise FEV1 was associated with a higher risk of EIB (last quartile six times higher risk compared to highest quartile (OR 6.1 [95%CI 2.5-14.5]). The severity of EIB is significantly greater in children with overweight and obesity compared to non-overweight asthmatic children. Furthermore, this study shows that the BMI-z-score, even with a normal weight, is strongly associated with the incidence of EIB in asthmatic boys.

Pre-Exercise Hyperpnea Attenuates Exercise-Induced Bronchoconstriction Without Affecting Performance.

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.

Aberrant small airways function relates to asthma severity in young children

BackgroundFrequency dependence of resistance (R5-20) assessed by impulse oscillometry (IOS) is suggested to be a measure of small airways. Small airways involvement during induced bronchoconstriction has been shown to reflect severity of asthma in adults. ObjectiveOur aim was to evaluate if methacholine (Mch) induced changes in R5-20 are associated with the severity of exercise induced bronchoconstriction (EIB) in young children. MethodsA total of 109 children aged 3–8 years were studied, 95 with obstructive symptoms and 14 in good health, to assess small airways function during a Mch challenge. R5-20 and other IOS resistance and reactance parameters were measured at baseline and after the Mch challenge. In a standardized exercise test, the children were grouped according to the severity of EIB expressed as the percentage increase in resistance at 5 Hz (ΔR5) after exercise, indicating either no EIB (ΔR5 < 40%, n = 84), moderate EIB (ΔR5 40–80%, n = 13) and severe EIB (ΔR5 > 80%, n = 12). ResultsThe baseline R5-20 was not associated with the severity of EIB, but during Mch induced bronchoconstriction the change in R5-20 was significantly higher in children with severe EIB (2.61 fold increase) than in children with moderate EIB (1.48) or no EIB (1.74, p = 0.036). No significant associations were found in changes of other IOS parameters. The children with severe EIB also used more short-acting beta-agonists during the past two months than the other two groups (p < 0.001). ConclusionFrequency dependence of resistance (R5-20) measured by IOS during the Mch induced bronchoconstriction and more frequent use of beta-agonists are associated with severe EIB in young children.

Exercise-induced Bronchoconstriction

The invitation by the editor, Rafeul Alam, to guest edit this issue on exercise-induced bronchoconstriction (EIB) allowed me to bring together investigators from physiology to cellular biology of EIB. The preface contains information on how some of the contributors came together and identifies some conferences that helped broaden the scientific research in EIB in asthmatic children to include healthy elite athletes. The contributors come from Australia, Canada, Denmark, England, France, Israel, Sweden, Netherlands, and the United States and trained in pediatric, respiratory, and sports medicine and science. Most have either obtained a doctoral degree in EIB or supervised one. My first encounter with EIB was at Royal Prince Alfred Hospital, in Sydney, in 1968. In January 1970 I started research in EIB with Simon Godfrey in the Department of Paediatrics at the Brompton Hospital in London. Over the next 3 years, under Simon’s enthusiastic guidance, a group of us carried out many studies on various aspects of EIB. In 1968 Ken Fitch from Perth, Australia observed severe EIB when supervising an exercise test on an 18-year-old asthmatic Olympic swimmer, who 3 months later won an Olympic Gold Medal in Mexico. This induced Ken to do his MD in EIB. Both Simon and Ken’s laboratories were coincidentally investigating the effect of different forms of exercise to provoke EIB. In 1971, both laboratories reported running as the most provocative exercise. Being ahead of their time, Ken and Simon wrote an article in 1976 on the topic of Asthma and Athletic Performance. They now celebrate the 50 years of research since the modern description of EIB in children by R.S. Jones of Liverpool, United Kingdom, in 1962. In 1973 Simon moved to the Hammersmith Hospital and later, in 1977, to Israel, where he continued his studies, among many others, on refractoriness and EIB. The article by Larsson and coworkers discusses these early studies and presents a new hypothesis to explain refractoriness following EIB.

Effects of dietary induced weight loss on exercise‐induced bronchoconstriction in overweight and obese children

Previous studies showed that obesity in asthmatic children is associated with more severe exercise-induced bronchoconstriction (EIB), compared with non-obese asthmatic children. This study investigates the effect of weight loss on EIB in overweight and obese asthmatic children. In this intervention study, children aged 8-18 years with EIB and moderate to severe overweight, followed a diet based on healthy daily intake for 6 weeks. Before and after the diet period they underwent an exercise challenge test in cold air. Primary outcome was change in exercise-induced fall in FEV1 and relation between weight loss and EIB. Secondary outcomes were changes in recovery of FEV1 ("area under the curve"; AUC), fraction of exhaled nitric oxide (FeNO) and scores of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and Asthma Control Questionnaire (ACQ). Twenty children completed the study. After the diet period, weight, and body mass index (BMI) were significantly reduced (changes respectively -2.6% and -1.5 kg/m(2), P < 0.01). There was a significant improvement of the percentage exercise-induced fall in FEV1 (30.6% vs. 21.8%, P < 0.01), AUC and PAQLQ score. The reduction in BMI z-score was significantly related to the reduction in the percentage exercise-induced fall in FEV1 in children that lost weight (r = 0.53, P = 0.03). There were no changes in FeNO and ACQ. Dietary induced weight loss in overweight and obese asthmatic children leads to significant reduction in severity of EIB and improvement of the quality of life. The reduction in BMI z-score is significantly related to the improvement of EIB.

Baseline Predictors of Placebo Response in Exercise-Induced Bronchoconstriction (EIB): Pooled Regression Analysis >From Three Studies of Montelukast in EIB

Background. Exercise-induced bronchoconstriction (EIB) can be variable in its presentation and severity. Evaluating patterns of placebo response and patient-related factors driving placebo response could facilitate more efficient clinical trials for EIB. Methods. Data were pooled from three randomized, double-blind, crossover trials evaluating single-dose montelukast 10 mg or placebo in patients (N = 160) 15–45 years of age with EIB, defined as maximum % fall in forced expiratory volume in one second (FEV1) ≥20% after two screening exercise challenges. Serial exercise challenges were performed at 2, 8.5–12, and 24 h postdose. The authors evaluated the distribution and variability of placebo response. They also evaluated possible drivers of response, analyzing all baseline patient demographic and prerandomization screening visit pulmonary function data as single covariates in a simple univariate regression model for maximum % fall in FEV1 while on placebo at 2 h postdose. All covariates with p values <.1 were entered into both stepwise forward and backward regression procedures to select the “best” model. Results. Placebo response was variable, and showed a significant non-normal distribution (p < .001). Significant predictors of a greater response to placebo included: higher screening FEV1 % predicted (p <.001), smaller maximum % fall in FEV1 in screening (p < .001), shorter time to recovery in screening (p = .007), more asthma-related health care visits in the previous year (p = .004), older age (p = .001), less frequent asthma awakenings in the previous month (p = .003), and less frequent asthma symptoms in the past year (p = .011). Conclusion. Predictors of a larger placebo response were generally markers of less severe asthma and/or EIB. This may be related to EIB variability, spontaneous improvement, or the extent of placebo response relative to the outcomes in less severe patients.

Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction

IL-13 is a pivotal cytokine in allergic inflammation and bronchial hyperresponsiveness, and is known to influence leukotriene levels. We investigated whether IL-13 polymorphisms may be associated with clinical phenotypes and drug responsiveness to the leukotriene receptor antagonist (LTRA) in Korean asthmatic children with exercise-induced bronchoconstriction (EIB). We enrolled 242 normal controls and 374 patients with asthma. Of the asthmatic patients, 100 performed exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks and included 80 subjects in drug responsiveness analysis. We assessed IL-13 polymorphisms (-1512A/C, -1112C/T, +2044G/A) through PCR-restriction fragment length polymorphism analysis. Significantly higher total IgE levels and maximum percent fall in forced expiratory volume in 1 s (FEV1) (%) after exercise challenge test were found in asthmatic patients carrying one or two copies of the IL-13 +2044A versus those homozygous for +2044G (P=0.011 and 0.040, respectively). We further noted a correlation of total IgE with maximum percent fall in FEV1 (%) in asthmatic patients, as well as a reverse correlation with improvement of maximum percent fall in FEV1 (%) after exercise challenge tests. Finally, we observed a significant association between responsiveness to montelukast and IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms. The IL-13 +2044G/A polymorphism may be associated with atopy and EIB severity in Korean children with EIB, and thus could potentially be considered as a disease-modifying gene. Moreover, the IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms seem to be associated with LTRA drug responsiveness, and thus might prove useful as a target for modulation of LTRA drug responsiveness.

Sputum Eosinophils and the Response of Exercise-Induced Bronchoconstriction to Corticosteroid in Asthma

The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind, crossover study arms (13 subjects in each arm). Each arm compared two dose levels of inhaled ciclesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks, as follows: (1) 40 vs 160 microg daily; and (2) 80 vs 320 microg daily. Baseline and weekly assessments with exercise challenge and sputum analysis were performed. Data were pooled and demonstrated that 10 subjects had baseline sputum eosinophilia >or= 5%. Only high-dose ICS therapy (ie, 160 and 320 microg) significantly attenuated the sputum eosinophil percentage. Sputum eosinophil percentage significantly correlated with EIB severity, and predicted the magnitude and temporal response of EIB to high-dose therapy, but not to low-dose therapy (ie, 40 and 80 microg). Low-dose ICS therapy provided a significant reduction in EIB at 1 week, with little additional improvement thereafter, irrespective of baseline sputum eosinophil counts. In contrast, high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of < 5%. The difference between the eosinophilic groups in the magnitude of improvement in EIB was evident after the first week of high-dose ICS therapy and increased with time. These results suggest that eosinophilic airway inflammation may be important in modifying the severity of EIB and the response to ICS therapy. Measurements of sputum eosinophil percentage may, therefore, be useful in predicting the magnitude and temporal response of EIB to different dose levels of ICSs. clinicaltrial.gov; Identifier: NCT00525772.

Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction

The pathogenesis of exercise-induced bronchoconstriction (EIB) involves the release of mediators from several airway cells in response to exercise challenge, but the mechanism leading to airflow obstruction during EIB is incompletely understood. To evaluate the role of secreted mucin in the pathogenesis of EIB. Induced sputum was collected at baseline and 30 minutes after exercise challenge in patients with asthma with EIB. The expression of gel-forming mucins and epidermal growth factor receptor ligands were assessed by quantitative polymerase chain reaction. Secreted mucin 5AC (MUC5AC), the eicosanoids cysteinyl leukotrienes (cysLTs) and 15S-hydroxyeicosatetraenoic acid (15S-HETE), and tachykinins neurokinin A (NKA) and substance P (SP) were measured in induced sputum supernatant. Among the gel-forming mucins, MUC5AC was expressed at the highest level. The gene expression of MUC5AC increased after exercise challenge compared with baseline and was associated with EIB severity by regression analysis. The relative levels of MUC5AC in induced sputum increased from a geometric mean of 9.5 at baseline to 18.4 postexercise challenge. Associations between the levels of MUC5AC and cysLTs and between the levels of cysLTs and NKA postexercise challenge were identified by regression analysis. These data indicate that (1) the predominant gel-forming mucin expressed in induced sputum of patients with asthma with EIB is MUC5AC; (2) an increase in MUC5AC gene expression and release of MUC5AC protein occurs after exercise challenge; and (3) MUC5AC release may occur through the cysLT-associated activation of sensory airway nerves.

Nedocromil sodium for preventing exercise-induced bronchoconstriction.

Exercise-induced asthma causes cough, dyspnea, wheeze and chest tightness. Management of focuses on prevention through pharmaco-therapy and alternate strategies. Single use, pre-exercise beta2-agonists and non-steroidal anti-inflammatory agents such as the cromones are the most common treatments. The objective of this review was to assess the effects of a single dose of nedocromil sodium to prevent exercise-induced bronchoconstriction. We searched the Cochrane Airways Group trials register, the Cochrane Controlled Trials Register, Current Contents, review articles, textbooks and reference lists of articles. We also contacted the drug manufacturer and primary authors for additional citations. Randomised trials comparing a single dose of nedocromil sodium with placebo to prevent exercise-induced bronchoconstriction in people over six years of age. Trial quality assessment and data extraction were conducted independently by two reviewers. Study authors were contacted for confirmation of data. Twenty randomised controlled trials involving 280 participants were identified. 15-60 min following inhalation of 4 mg nedocromil, the maximum fall in forced expiratory volume in one second due to exercise was improved by 15.6%, (95% CI:13.2 to 18.1) compared to the placebo response. The maximum percentage fall in peak expiratory flow rate was of the same magnitude (weighted mean difference 15.0%; 95% CI 8.3 to 21.6). Nedocromil shortened the time to recover lung normal function from more than 30 minutes with placebo to less than 10 minutes with the drug. The relative magnitude of its effect was greatest in patients with more severe exercise-induced bronchoconstriction (defined as an exercise-induced fall in lung function > 30% from baseline). There were no significant adverse effects reported. Nedocromil sodium used before exercise appears to reduce the severity and duration of exercise-induced bronchoconstriction. This effect appears to be more pronounced in people with severe exercise-induced bronchoconstriction.

Role of Alpha-Adrenergic Receptors in Exercise-Induced Bronchoconstriction

The role of alpha-adrenergic receptors in exercise-induced bronchoconstriction (EIB) was studied. 9 asthmatic patients with a marked degree of EIB (group I) and 6 asthmatic patients with no or a less severe EIB (group II) were investigated and compared with 8 healthy control persons. Pulse rate, airway resistance and end-expiratory thoracic gas volume were measured at rest and immediately and 15 min after exercise. Group I subjects showed a significant inhibition of EIB after alpha-adrenergic blockade with phentolamine (10 mg as aerosol) and after cholinergic blockade with an atropine-ester (60 mg as aerosol). In 7 of 9 patients who had received phentolamine, and in 3 of 6 patients who had received atropine-ester, the EIB was completely suppressed. In group II the administration of propranolol (40 mg orally) produced a significant increase in EIB. The effect of propranolol could be inhibited by the addition of alpha-adrenergic blockade with phentolamine (10 mg as aerosol). The control subjects had no measurable EIB, even after the administration of propranolol (40 mg orally). It is concluded that, in addition to the vagal system, an activated alpha-adrenergic system is involved in the phenomenon of EIB.