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Background: Exercise is one of the most common triggers of bronchoconstriction and affects up to 80% of children with asthma., Objective: The purpose of this randomized, double-blind, placebo-controlled study was to assess the effectiveness of treatment with ciclesonide 160 microgram, either alone, with a higher dose, with a leukotriene receptor antagonist (LTRA), or with a long-acting beta-agonist (LABA) in children with asthma with postexercise-induced symptoms., Methods: Eighty adolescents, ages 1218 years, with asthma and postexercise symptoms were enrolled. Children were treated in one of four treatment groups: ciclesonide 160 microgram daily dose (cic 160), ciclesonide 320 microgram daily dose (cic 320), ciclesonide 160 microgram daily dose combined with montelukast (cic + LTRA), or ciclesonide 160 microgram daily combined with formoterol (cic + LABA). The impact of treatment on clinical symptoms, maximum percentage decrease in forced expiratory volume in 1 second after intense exercise effort, fractional exhaled nitric oxide in exhaled breath, and the contribution of inflammatory mediators in exhaled breath condensate were assessed., Results: In children with asthma and with postexercise symptoms, 8-week daily administration of ciclesonide 320 microgram, ciclesonide 160 microgram plus LABA, and ciclesonide 160 microgram alone decreased daytime symptoms; decrease in maximal fall in forced expiratory volume in 1 second reached the level of significance in the cic 320, cic + LABA, and cic + LTRA groups. A higher prevalence of positive responses to treatment after addition of an LTRA or LABA to ciclesonide 160 microgram for patients with exercise treadmill challengeinduced clinical symptoms only was revealed., Conclusion: Monotherapy with ciclesonide 320 microgram can be as effective as combined therapy in reducing exercise-induced bronchoconstriction. We revealed a higher prevalence of positive responses to treatment after the addition of LTRA or LABA to ciclesonide 160 microgram for patients with exercise treadmill challengeinduced clinical symptoms only. ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.ClinicalTrials.gov"www.ClinicalTrials.gov/ext-link NCT01798823.

Rationale: Inhaling medication in a standard body posture leads to impaction of particles in the sharp angle of the upper airway. Stretching the upper airway by extending the neck in a forward leaning body posture may improve pulmonary deposition. A single dose of inhaled corticosteroids (ICS) offers acute, but moderate protection against exercise induced bronchoconstriction (EIB). This study investigated whether inhaling a single dose of ICS in a forward leaning posture improves this protection against EIB., Methods: 32 Asthmatic children, 5-16 years, with EIB (Median fall in FEV1 or FEV0.5 30.9%) performed two exercise challenge tests (ECT's) with spirometry in a single blinded cross-over trial design. Children inhaled a single dose of 200 μg beclomethasone dipropionate (BDP) 4 h before the ECT, once in the standard posture and once with the neck extended in a forward leaning posture. Spirometry was also performed before the inhalation of the single dose of BDP., Results: Inhalation of BDP in both body postures provided similar protection against EIB (fall in FEV1 or FEV0.1 in standard posture 16.7%; in forward leaning posture 15.1%, p = 0.83). Inhaling ICS in a forward leaning posture significantly delayed EIB compared to inhaling in the standard posture (respectively 2.5 min ± 1.0 min vs. 1.6 min ± 0.8 min; difference 0.9 min (95CI 0.25; 1.44 min); p = 0.01)., Conclusion: Inhalation of a single dose BDP in both the forward leaning posture and the standard posture provided effective and similar protection against EIB in asthmatic children, but the forward leaning posture resulted in a delay of EIB., Register: NTR3432 (www.trialregister.nl)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Exercise-induced bronchoconstriction (EIB) describes the phenomenon of transient airway narrowing in association with physical activity. Although it may seem likely that EIB would have a detrimental impact on athletic performance, this has yet to be established., Objectives: The aim of this review is to provide a systematic appraisal of the current status of knowledge regarding EIB and exercise performance and to highlight potential mechanisms by which performance may be compromised by EIB., Data Sources and Study Selection: PubMed/Medline and EBSCO databases were searched up to May 2014 using the search parameter: [('exercise' OR 'athlete') AND ('asthma' OR 'bronchoconstriction' OR 'hypersensitivity') AND 'performance']. This search string returned 243 citations. After systematically reviewing all of the abstracts, 101 duplicate papers were removed, with 132 papers excluded for not including an exercise performance outcome measure., Results: The remaining ten studies that met the initial criteria were included in this review; six evaluated the performance of physically active individuals with asthma and/or EIB while four assessed the effects of medication on performance in a comparable population., Conclusion: The evidence concludes that whilst it is reasonable to suspect that EIB does impact athletic performance, there is currently insufficient evidence to provide a definitive answer.

Elite athletes are often subjected to endurance training in the environment in which they are chronically exposed to pollutants/irritants, allergens or cold air. These factors lead to an increased risk of upper and lower respiratory tract dysfunction. The diagnosis of asthma is crucial in elite athletes because of potential implications on athlete's general well-being as well as their competitive ability. Symptoms of asthma in elite athletes are not necessarily associated with the classic features of asthma seen in general population. Other clinical entities can create symptoms similar to those of asthma and therefore can lead to an incorrect diagnosis and ineffective treatment. The diagnosis requires a combination of symptoms and positive laboratory tests. Currently, there is no evidence that the treatment of asthma in athletes should be different from the treatment of asthma in non-athletes. However, some specific issues need to be considered in the elite athletes, such as compliance with the rules of World Anti-Doping Agency and International Olympic Committee.

Background: Mannitol- and exercise bronchial provocation tests are both used to diagnose exercise-induced bronchoconstriction. The study aim was to compare the short-term treatment response to budesonide and montelukast on airway hyperresponsiveness to mannitol challenge test and to exercise challenge test in children and adolescents with exercise-induced bronchoconstriction., Methods: Patients were recruited from a paediatric asthma rehabilitation clinic located in the Swiss Alps. Individuals with exercise-induced bronchoconstriction and a positive result in the exercise challenge test underwent mannitol challenge test on day 0. All subjects then received a treatment with 400 μg budesonide and bronchodilators as needed for 7 days, after which exercise- and mannitol-challenge tests were repeated (day 7). Montelukast was then added to the previous treatment and both tests were repeated again after 7 days (day 14)., Results: Of 26 children and adolescents with exercise-induced bronchoconstriction, 14 had a positive exercise challenge test at baseline and were included in the intervention study. Seven of 14 (50%) also had a positive mannitol challenge test. There was a strong correlation between airway responsiveness to exercise and to mannitol at baseline (r = 0.560, p = 0.037). Treatment with budesonide and montelukast decreased airway hyperresponsiveness to exercise challenge test and to a lesser degree to mannitol challenge test. The fall in forced expiratory volume in one second during exercise challenge test was 21.7% on day 0 compared to 6.7% on day 14 (p = 0.001) and the mannitol challenge test dose response ratio was 0.036%/mg on day 0 compared to 0.013%/mg on day 14 (p = 0.067)., Conclusion: Short-term treatment with an inhaled corticosteroid and an additional leukotriene receptor antagonist in children and adolescents with exercise-induced bronchoconstriction decreases airway hyperresponsiveness to exercise and to mannitol.

Exercise-induced bronchoconstriction (EIB) describes the transient narrowing of the airways during, and particularly after exercise and occurs commonly in asthmatic individuals. Limitation of exercise capacity is a frequent complaint in all age groups, and severity of EIB ranges from mild impairment of performance to severe bronchospasm and a large reduction in FEV1. Treatment of EIB varies from daily to less frequent therapy, depending on the level of activity. In this article, the authors evaluate the treatment possibilities before, during, and after exercise. They also review medications currently used to treat EIB., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Exercise-induced bronchoconstriction (EIB) describes acute airway narrowing that occurs as a result of exercise. EIB occurs in a substantial proportion of patients with asthma, but may also occur in individuals without known asthma., Methods: To provide clinicians with practical guidance, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB and to develop evidence-based guidelines for the diagnosis and treatment of EIB. The evidence was appraised and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach., Results: Recommendations for the treatment of EIB were developed. The quality of evidence supporting the recommendations was variable, ranging from low to high. A strong recommendation was made for using a short-acting β(2)-agonist before exercise in all patients with EIB. For patients who continue to have symptoms of EIB despite the administration of a short-acting β(2)-agonist before exercise, strong recommendations were made for a daily inhaled corticosteroid, a daily leukotriene receptor antagonist, or a mast cell stabilizing agent before exercise., Conclusions: The recommendations in this Guideline reflect the currently available evidence. New clinical research data will necessitate a revision and update in the future.

Objective: International guidelines recommend short- (SABA) or long-acting b-agonists for the prevention of bronchoconstriction after exercise (EIB) in patients with exercise-induced asthma (EIA). However, other drugs are still in discussion for the prevention of EIB. We investigated the efficacy of a combination of inhaled sodium cromoglycate and the β-mimetic drug reproterol versus inhaled reproterol alone and both versus inhaled placebo in subjects with exercise-induced asthma (EIA)., Methods: The study aimed to prove the preventive effect of a combination of 1-mg reproterol and 2-mg disodium cromoglycate (DSCG) and its single components vs. placebo, measuring the decrease of FEV1 after a standardized treadmill test in 11 patients with recorded EIA. The study medication was twice as high as those of drugs which are commercially available (e.g., Allergospasmin®, Aarane®)., Results: The results revealed that the combination of reproterol and DSCG was significantly effective against a decrease of FEV1 after a standardized exercise challenge test (ECT) compared to placebo. The short-acting b-agonist reproterol alone had almost the same effectiveness as the combination of reproterol and DNCG. The difference between the combination with DNCG and reproterol alone was less than 10% and insignificant (p 0.48). DNCG alone did not show a difference in the effectiveness compared to placebo., Conclusion: Prevention of EIA with the combination of reproterol and DSCG or with reproterol only is effective. An exclusive recommendation in favor of the combination cannot be given due to the low difference in the effectiveness versus reproterol alone. Due to the limited number of subjects and some probands showing protection under DSCG, it cannot be completely excluded that there is some preventive power of DSCG in individual cases.

Introduction: Despite international consensus and clearly written guidelines urging wider use of corticosteroids or combinations of inhaled short- and long-acting β-agonists (SABA and LABA) and corticosteroids in persistent asthma, prescribing patterns and compliance rates fall far short of recommendations., Objectives: The failure to use steroids more aggressively is due, in part, to their side effects, even with inhaled forms of the drug. There is a role for expanded use of sodium cromolyn in asthma. Its potent anti-inflammatory effects, lack of side effects, and acceptable dosing and method of delivery, as well as its special role in exercise-induced asthma, make it a very suitable choice in the initial therapy for control of asthma., Conclusion: Compared to SABA and LABA, cromoglycates alone are unsuspicious of being used to enhance physical performance.

Objective and Methods: Asthma is often reported by elite athletes, especially endurance athletes. The aim of this article is to review current knowledge of mechanisms and management of exercise-induced asthma (EIA) in adult elite athletes., Results: The mechanisms underlying EIA is incompletely understood, but the two prevailing hypotheses are the hyper-osmolarity and the thermal hypothesis. Both hypotheses consider inflammation and activation of mast cells as being crucial for the development of EIA, although the assumed mechanisms triggering the inflammatory response differ. Objective testing is of utmost importance in the diagnosis of EIA in elite athletes. Management of EIA can be divided into pharmacologic and non-pharmacologic treatment. The basic principles for the treatment of EIA in elite athletes should be as for any asthmatic individual, including use of inhaled corticosteroids (ICS), β(2)-agonists, and leukotriene antagonists. However, evidence suggests that daily use of β(2)-agonists might lead to the development of tolerance. ICS therapy is, due to its anti-inflammatory effects, the recommended primary therapy for EIA also in elite athletes. All doctors treating individuals with asthma, especially elite athletes, should remain updated on doping aspects of asthma therapy. Non-pharmacologic management of EIA in elite athletes includes physical warm-up, which takes advantage of the refractory period following an attack of EIA, whereas high intake of antioxidants may reduce airway inflammation. Wearing heat masks, specially designed for outdoor winter athletes, might protect against bronchoconstriction triggered by inhalation of cold and dry air., Conclusion: EIA in elite athletes should be managed as in any individual with asthma, but the risk of developing tolerance to bronchodilators as well as doping aspects should always be taken into account.

Single-dose montelukast attenuates exercise-induced bronchoconstriction (EIB) in adults within 2 hours postdose and lasting through 24 hours. This study evaluated the onset and duration of EIB attenuation in children after a single dose of montelukast. A randomized, double-blind, placebo-controlled, two-period crossover study was performed. Patients (n = 66) aged 4-14 years, with preexercise forced expiratory volume in 1 second of (FEV(1)) ≥70% predicted and maximum percentage fall in FEV(1) of ≥20% at two screening exercise challenges were eligible. Patients were to receive single-dose montelukast (4 or 5 mg) or placebo before performing standardized exercise challenges at 2 and 24 hours postdose. A 3- to-7-day washout separated the two crossover periods. The primary end point was maximum percentage fall in FEV(1) after exercise challenge 2 hours postdose. Secondary end points included maximum percentage fall in FEV(1) after the 24-hour postdose challenge; each of the following at 2 and 24 hours postdose-maximum percentage fall in FEV(1) categorized as <10%, 10-20%, or >20%; area under the curve (AUC) during 60 minutes postchallenge; time to recovery of FEV(1) to within 5% of preexercise baseline; and need for rescue medication. The mean maximum percentage fall in FEV(1) after the 2-hour postdose exercise challenge was significantly attenuated after single-dose montelukast compared with placebo (15.35% versus 20.00%; p = 0.020). Montelukast was also significantly more effective than placebo for maximum percentage fall after the 24-hour challenge (12.92% versus 17.25%; p = 0.005), the categorized maximum percent fall in FEV(1) at 2 hours (p = 0.034), and AUC at 2 hours (p = 0.022) and 24 hours (p = 0.013). Single-dose montelukast provided rapid and sustained EIB attenuation in children. Clinicaltrials.gov identifier: NCT00534976.

Purpose: Conjugated linoleic acid (CLA) has been reported to modify the inflammatory response associated with allergic airway disease, primarily in animal models. To extend these observations to humans, the effect of short-term CLA supplementation on the severity of exercise-induced bronchoconstriction (EIB) was investigated in asthmatics., Methods: Six subjects with physician-diagnosed asthma and EIB began the study on their usual diet, to which was added 4.8 g CLA/d for 8 wk. Pulmonary-function tests were administered before and after eucapnic voluntary hyperventilation (EVH) challenge at the commencement (Week 0) and conclusion of the treatment period (Week 8). Pre- and 90 min post-EVH challenge, urine was assayed for the presence of cysteinyl leukotrienes (LT) C4-E4 and 9α, 11β-prostaglandin (PG) F2., Results: Pre- to post-EVH forced expiratory volume in 1 s (FEV1) did not significantly differ (p > .05) from Week 8 to Week 0. The pre- to post-EVH decline in FEV1 at Week 8 (-29.6% ± 6.6%) was not significantly different (p > .05) from that at Week 0 (-32.0% ± 5.5%). Area under the curve of FEV1 plotted against time from zero to 60 min (AUC0-60) was unaltered at Week 8 (-931% ± 350% change per minute) compared with Week 0 (-1,090% ± 270% change per minute). CLA supplementation did not alter forced midexpiratory flow, forced vital capacity (FVC), or FEV1/FVC. In addition, post-EVH urinary LTC4-E4 and 9α, 11β-PGF2 were unchanged after CLA supplementation., Conclusion: Daily supplementation of 4.8 g CLA for 8 wk does not attenuate airway inflammation or hyperpnea-induced bronchoconstriction in asthmatic individuals.

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.

Background and Objective: Exercise-induced wheeze (EIW) is common. Several treatment options exist. Patients with low fraction of exhaled nitric oxide (F(E)NO) are unlikely to be steroid-responsive and might benefit from non-steroidal therapies. We assessed: the efficacy of cromoglycate, formoterol and montelukast in patients with EIW and low F(E)NO (<35 ppb) in a randomized cross-over trial, and the efficacy of inhaled corticosteroid in a high F(E)NO (>35 ppb) group., Methods: Patients had EIW and airway hyperresponsiveness (AHR) to mannitol and/or exercise. Those with low F(E)NO (n = 19) received cromoglycate (20 mg inh. bd + before challenge tests), formoterol (12 microg inh. bd + before challenge tests) and montelukast (10 mg p.o. od), each for 2 weeks. Those with high F(E)NO (n = 20) took inhaled fluticasone (500 microg) daily for 4 weeks. Primary end-points were: 50% reduction in maximum FEV(1) %fall (clinical protection) and decrease in AHR to mannitol., Results: In patients with low F(E)NO, cromoglycate, formoterol and montelukast significantly decreased AHR to mannitol in 63%, 61% and 47% of patients, respectively. In this group, the magnitude of exercise-induced bronchoconstriction (EIB) was significantly reduced with montelukast and formoterol; between-treatment differences were not significant. Of 6/19 with low F(E)NO and EIB, protection occurred in 67% (cromoglycate), 83% (formoterol) and 50% (montelukast), respectively. In the high F(E)NO group, AHR to mannitol and EIB decreased significantly with fluticasone (P < 0.001, P = 0.005, respectively), and protection occurred in 7/8 (88%) with EIB., Conclusions: In patients with EIW and low F(E)NO, the number of 'responders' to cromoglycate, formoterol and montelukast was similar. In a high F(E)NO population the response to inhaled corticosteroid was highly significant and comparable to previous studies.

Background: Exercise-related respiratory symptoms in the diagnosis of exercise-induced bronchoconstriction (EIB) have poor predictive value. The aim of this study was to evaluate how athletes presenting with these symptoms are diagnosed and managed in primary care., Methods: An electronic survey was distributed to a random selection of family practitioners in England. The survey was designed to assess the frequency with which family practitioners encounter adults with exercise-related respiratory symptoms and how they would approach diagnostic work-up and management. The survey also evaluated awareness of and access to diagnostic tests in this setting and general knowledge of prescribing asthma treatments to competitive athletes., Results: 257 family practitioners completed the online survey. One-third of respondents indicated they encountered individuals with this problem at a frequency of more than one case per month. Over two-thirds of family practitioners chose investigation as an initial management strategy, while one-quarter would initiate treatment based on clinical information alone. PEFR pre- and post-exercise was the most commonly selected test for investigation (44%), followed by resting spirometry pre- and post-bronchodilator (35%). Short-acting beta2-agonists were the most frequently selected choice of treatment indicated by respondents (90%)., Conclusion: Family practitioners encounter individuals with exercise-related respiratory symptoms commonly and although objective testing is often employed in diagnostic work-up, the tests most frequently utilised are not the most accurate for diagnosis of EIB. This diagnostic approach may be dictated by the reported lack of access to more precise testing methods, or may reflect a lack of dissemination or awareness of current evidence. Overall the findings have implications both for the management and hence welfare of athletes presenting with this problem to family practitioners and also for the competitive athletes requiring therapeutic use exemption.

Jenny B. is an active 12-year-old white female who recently stopped participating in junior high school track because of respiratory symptoms she experiences while running. On presentation to her pediatrician's office for a consultation, it immediately became apparent that she was anxious to rejoin her team to compete. This article will navigate through a patient case and explore multiple clinical approaches to exercise-induced broncho-spasm from diagnosis to treatment. As clinicians, our goal is to partner with all patients who experience asthma or respiratory symptoms, enabling them to have a life without limitations. Let us review Jenny B.'s case and examine what might be the best approach to get her back on track.

Exercise is the most common trigger of bronchospasm in children with asthma. Exercise-induced bronchoconstriction (EIB) occurs in up to 90% of individuals with asthma who are not under antiinflammatory treatment and in about 40% of those with allergic rhinitis. EIB may be an overwhelming problem in childhood and adolescence, when physical activity is a prominent component of daily life. The importance for those with asthma to maintain regular physical activity is recognized by asthma guidelines, which include the recommendation of full participation in sporting activities in their goals for the management of asthma. Cysteinyl leukotrienes, which are derivatives of the 5-lipoxygenase pathway of arachidonic acid metabolism, are important mediators of airway allergic inflammation and have a role in the pathogenetic mechanism of EIB. Montelukast sodium (Singulair, Merck & Co.) is a selective and orally active leukotriene receptor antagonist with demonstrated activity for treating asthma and allergic rhinitis. The effect of this drug in the prevention of EIB has been evaluated in a variety of studies in adults as well as in children. Both single-dose and regular-treatment studies showed that montelukast provides effective protection against EIB. Furthermore, chronic treatment with montelukast does not induce tolerance to the bronchoprotective effect over time. This aspect is particularly relevant for children, who tend to be active at frequent and irregular intervals throughout the day, and who therefore may benefit from around-the-clock pharmacologic protection., (Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.)

Purpose: Data from the general population suggest that habitual exercise decreases bronchial responsiveness, but the possible role of exercise in asthmatics is undefined. The leukotriene receptor antagonist montelukast decreases bronchial responsiveness and exercise-induced symptoms in asthmatic children. This randomized study in children with mild asthma evaluated the combined effects of aerobic training for 12 wk and montelukast or placebo on bronchial responsiveness (BHR) to methacholine, exercise-induced bronchoconstriction (EIB), inflammatory markers in exhaled breath condensate (EBC), and asthma exacerbations., Methods: Fifty children (mean age +/- SD: 10.2 +/- 2.4 yr) with mild stable asthma were randomly assigned to placebo (N = 25) or montelukast (N = 25). Before and after training, we assessed BHR and EIB and markers of airway inflammation-that is, exhaled nitric oxide (eNO), pH, and cysteinyl-leukotriene concentration-in EBC., Results: Training increased maximal workload and peak minute ventilation. After training, the methacholine dose causing a 20% fall in FEV1 (PD20) increased in both groups. A decreased slope of FEV1 decline at increasing methacholine dose was found only in montelukast-treated children. EIB prevalence halved after training in both groups (EIB + children, placebo group: 10 pretraining, 4 posttraining; EIB + children, montelukast group: 8 pretraining, 5 posttraining; P < 0.05 by chi on all children). Resting eNO was unaffected, whereas the pH of EBC decreased after training in both groups. Cysteinyl-leukotriene concentrations were low in most children at both times. During training, montelukast-treated children showed fewer asthma exacerbations compared with the same period of the previous year., Conclusions: In children with mild stable asthma, exercise training decreased bronchial responsiveness to methacholine. Montelukast also decreased bronchial reactivity (FEV1 slope) and protected against exacerbations, suggesting a beneficial synergistic action of these two interventions in mild asthma.

Background: Asthma is a chronic disease with a heterogeneous phenotype that is often associated with allergic sensitization in childhood. The earliest definable form of asthma is mild (intermittent or persistent), a severity level that may be characteristic of a majority of children with asthma. Several asthma controllers are indicated for use in children. International guidelines recommend the use of inhaled corticosteroids as the preferred controller therapy in mild persistent asthma., Objective: This article reviewed recent results from randomized, double-blind studies of children with mild asthma treated with montelukast, a leukotriene receptor antagonist that is approved for the treatment of asthma and allergic rhinitis in children and adults., Methods: A literature search of MEDLINE was conducted to gather relevant, English-language articles using search terms such as randomized controlled studies, double-blind studies, montelukast, leukotriene receptor antagonist, pediatric asthma, mild asthma, exercise-induced asthma, and bronchoconstriction. Recent articles (since 1998) that described the use of montelukast as a monotherapy were chosen for this review., Results: Relevant studies included a 48-week, placebo-controlled study of 2- to 5-year-old mild intermittent asthmatics (N = 549); a 12-week, placebo-controlled study of 2- to 5-year-old mild persistent asthmatics (N = 689); an analysis of a mild persistent asthmatic cohort (N = 138) from an 8-week, placebo-controlled study of 6- to 14-year-old asthmatics; a 12-month study comparing montelukast with fluticasone in 6- to 14-year-old mild persistent asthmatics (N = 949); and 3 placebo-controlled studies in children with exercise-induced asthma (N = 123). The results from these studies, encompassing end points measuring lung function and symptoms, found that montelukast provided effective and beneficial asthma control to children aged 2 to 14 years with mild asthma., Conclusion: The evidence suggests that montelukast is an effective monotherapy controller in children with mild asthma.

Asthma, exercise-induced bronchoconstriction, and airway hyper-responsiveness are often found in elite athletes, perhaps as a consequence of their sport or maybe because asthma is a common disorder in young adults. Inhaled beta2-agonists (IBA) are frequently used in elite athletes, but due to regulations introduced by the International Olympic Committee, the use of anti-asthmatic therapy might change. Drugs that make ergogenic effect persist are prohibited in all athletes, whether or not they take part in competitions and systemic steroids and beta2-agonists are among such drugs. On the other hand, opinion is more divided about the use of inhaled corticosteroids (ICS) and IBA. In humans, no effect has been found on the oxygen uptake, performance or distance run with therapeutic doses of IBA, either in asthmatics or non-asthmatics, whereas others report an ergogenic effect and better lung function of high doses of a beta2-agonist in non-asthmatics. Anti-asthmatic treatment is necessary for asthmatics, but should not be used by non-asthmatic elite athletes due to both possible systemic effects and furthermore, side effects of both ICS and IBA.

Objectives: To compare leukotriene antagonists (LTA) to other groups of drugs used in asthma and allergic rhinitis treatment., Sources: MEDLINE, LILACS and Cochrane Library., Keywords: leukotrienes, antileukotrienes, asthma treatment, allergic rhinitis treatment, asthma and allergic rhinitis. An attempt was made to group the main studies and reviews about this topic., Summary of the Findings: LTA are more efficient than placebo and enhance the effects of inhaled corticosteroids. The association of inhaled corticosteroids with long-acting Beta2 agonists is more efficient than the association of inhaled corticosteroids + LTA. Although use of LTA in acute asthma attacks and allergic rhinitis seems reasonable, more studies are needed to confirm this benefit. LTA reduce hospitalization time and the number of wheezing attacks in infants with acute viral bronchiolitis caused by respiratory syncytial virus, as well as recurrent wheezing after acute viral bronchiolitis. LTA are less efficient than intranasal corticosteroids for allergic rhinitis management. LTA are efficient in exercise-induced asthma, although they are not the first-line treatment., Conclusion: Controlled and randomized studies show that inhaled corticosteroids are the drugs of choice to treat persistent asthma and allergic rhinitis. There is not enough evidence to recommend the use of LTA as first-line drug (monotherapy) in children with asthma (level I). For children who cannot use inhaled corticosteroids, LTA may be a good alternative (level II).

Objective: To discuss the clinical efficacy and safety of formoterol when used to relieve symptoms of asthma and prevent exercise-induced bronchoconstriction (EIB)., Data Sources: A PubMed search was performed for articles published between 1997 and 2005 with the keywords formoterol, asthma, and long-acting beta2-adrenergic agonist, with cross-referencing to identify peer-reviewed journal articles., Study Selection: Published articles on the clinical use of formoterol for asthma or EIB were included as well as articles detailing the pharmacologic properties of the drug. To present a thorough review of the literature, published studies based on patient number, study design, or other measures of study quality were not excluded., Results: Formoterol is the only long-acting beta2-adrenergic agonist that combines a rapid onset of action (within 3 minutes) with a long duration of effect (approximately 12 hours). Clinically, as recommended by asthma treatment guidelines, formoterol in conjunction with inhaled corticosteroids (ICSs) is a preferred treatment for moderate to severe persistent asthma. Significant clinical data support the use of formoterol in combination with ICSs for the treatment of asthma, with studies demonstrating improved pulmonary function and symptom scores and decreased need for maintenance ICSs and short-acting beta2-adrenergic agonists (SABAs) as relief medication. Recent studies also demonstrate that use of formoterol as needed as relief medication is associated with a prolonged time to exacerbation, improved pulmonary function, and decreased asthma symptoms. When used as monotherapy, formoterol provides protection against EIB. Clinical data also demonstrate that formoterol is safe and well tolerated even in high doses, with an adverse event profile similar to that of SABAs., Conclusion: Overall, formoterol is safe and effective as adjunct controller therapy for moderate and severe persistent asthma and as monotherapy for EIB.

Asthma presents special challenges to both the athletes who have it and to their health care providers. This article briefly reviews the problem of asthma--especially exercise-induced asthma--in the competitive athlete, and then describes treatments that are effective in controlling asthma. Drug-doping regulations are explained, as is the worldwide impact of drug doping on competitive athletes who have asthma. This review concludes with recommendations for competitive athletes and their health care providers regarding how to deal with asthma in this patient population.

Background: Exercise induced bronchoconstriction (EIB) is common in elite athletes. Eucapnic voluntary hyperventilation (EVH) is a laboratory test recommended for the identification of EIB in athletes, secondary to a field exercise challenge. Montelukast attenuates EIB, but its protective effect against airway narrowing from EVH has not been investigated., Objective: To examine the effectiveness of montelukast after exercise and after EVH., Methods: A randomised, placebo controlled, double blind, crossover study was performed with 11 physically active EIB positive subjects (eight men, three women; mean (SD) age 22.8 (6.8) years). Six hours before each of the following challenges 10 mg montelukast or placebo was ingested: (a) a six minute, cold air (-3 degrees C) maximal effort work accumulation cycle ergometer exercise; (b) EVH, breathing 5% CO(2) compressed air at 85% maximal voluntary ventilation for six minutes. Spirometry was performed before and 5, 10, and 15 minutes after the challenge. At least 48 hours was observed between challenges., Results: No differences in forced expiratory volume in one second (FEV(1)) were found after the two challenges. Exercise and EVH resulted in falls in FEV(1) of 22.4 (18.0) and 25.6 (16.8) respectively. Falls in FEV(1) after montelukast were less than after placebo (10.6 (10.6) and 14.3 (11.3) after exercise and EVH respectively; p<0.05). Montelukast provided protection against bronchoconstriction (59% and 53%; p<0.05) for eight exercising subjects and 10 EVH subjects; no protection was afforded for three exercising and one EVH challenged subject., Conclusions: Both exercise and EVH were potent stimuli of airway narrowing. A single dose of montelukast provided reasonable protection in attenuating bronchoconstriction from either exercise or EVH. The similar protection by montelukast suggests that EVH is a suitable laboratory surrogate for EIB evaluation.

Background: Exercise is a common trigger of asthma symptoms in patients with persistent asthma., Objective: To evaluate the protective effect of fluticasone/salmeterol against exercise-induced bronchospasm., Methods: Multicenter, randomized, double-blind, parallel-group trial of 192 asthma patients who used moderate-dose inhaled corticosteroids. Patients (aged 12-50 years; mean forced expiratory volume in 1 second [FEV1], 78% of predicted at baseline) were randomized to receive fluticasone/salmeterol (250/50 microg twice daily) or fluticasone alone (250 microg twice daily) via Diskus for 4 weeks. Exercise challenge tests were performed 1 and 8.5 hours after administration of the first (day 1) and last (week 4) doses of blinded study medication., Results: On day 1 and at week 4, mean +/- SEM values for the maximal percentage decline in FEV1 1 hour after drug administration were 11.4% +/- 1.5% and 10.9% +/- 1.5% for fluticasone/salmeterol compared with 20.0% +/- 1.7% and 18.4% +/- 1.8% for fluticasone (P < .001). At 8.5 hours, mean +/- SEM values on day 1 and at week 4 were 11.6% +/- 1.4% and 8.9% +/1.1%, respectively, for fluticasone/salmeterol and 12.6% +/- 1.6% and 12.9% +/- 1.4%, respectively, for fluticasone (P = .01 at week 4). More fluticasone-treated patients did not complete the 8.5-hour exercise challenges (36% on day 1 and 33% at week 4) compared with the fluticasone/salmeterol group (18% each) (P < or = .01). Improvements in peak expiratory flow rate and albuterol rescue-free days were significantly greater with fluticasone/salmeterol vs fluticasone over weeks 1 to 4 (P < or = .03)., Conclusions: Consistent with the improvements in other measures of asthma control, long-term fluticasone/salmeterol therapy also provided protection against exercise-induced bronchospasm in patients with persistent asthma.

A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly increases drug delivery to the airways. Therefore, even low doses of HFA-BDP should be effective, and the present study assesses this. A randomised, double-blind, crossover study was used to compare the effect of placebo, HFA-BDP 50 microg or 100 microg given q.d. (QVAR(TM) Autohaler(TM); 3M Pharmaceuticals, St. Paul, MN, USA) on exercise-induced bronchoconstriction and exhaled nitric oxide (eNO). After a 14-day run-in, 25 children (5-14 yrs old) entered three 4-week treatment periods, separated by a 1-week washout. After each period, the fall in forced expiratory volume in one second (FEV1), after an exercise test, and eNO were measured. Significant treatment effects with no carry-over or period effects were seen for both eNO and maximum fall in FEV1 after exercise. Differences were seen between placebo (fall in FEV1=27.9%; eNO=14.4 parts per billion (ppb)) and either dose of HFA-BDP, but not between the two active doses (50 microg: fall in FEV1=20.8%, eNO=9.3 ppb; 100 microg: fall in FEV1=20.9%, eNO=8.9 ppb). In conclusion, low q.d. doses of hydrofluoroalkane-beclomethasone dipropionate reduced exhaled nitric oxide and exercise-induced bronchoconstriction. Further studies are needed to assess whether q.d. administration of beclomethasone dipropionate is as effective as b.i.d. administration.

Objectives: To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids (ICS) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction., Methods: A double-blind, placebo-controlled study was performed at 16 centers in the United States. Patients with asthma (n = 122, ages 15-58) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were randomized to receive either montelukast (10 mg once daily), salmeterol (50microg twice daily), or placebo for 4 weeks. Standardized spirometry after exercise challenge and beta2-agonist rescue was performed at baseline, week 1 and 4., Results: Maximum achievable forced expiratory volume in 1 s (FEV1) percent predicted after rescue beta2-agonist improved in the montelukast (+1.5%) and placebo (+1.2%) groups at 4 weeks, but diminished in the salmeterol (-3.9%) group (P < 0.001). Although pre-exercise FEV1 was greatest with salmeterol (P = 0.10), patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol (P < 0.001). Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol (P < 0.001). Five minutes after rescue beta2-agonist, 92% of patients taking montelukast and 68% of those taking placebo had recovered to pre-exercise levels, whereas only 50% of those taking salmeterol had recovered to pre-exercise levels., Conclusion: In patients whose asthma symptoms remain uncontrolled using ICS, addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinically meaningful protection against exercise-induced bronchoconstriction.

Unlabelled: Post exercise bronchospasm is a well-known phenomenon, particularly affecting children with asthma. In our own study post exercise bronchospasm occurred in 25-66% of children with asthma. The aim of the study was to evaluate the usefulness of cysteinyl leukotriene receptor antagonist -- montelukast (Mnt) in the prevention of post exercise bronchospasm., Material and Methods: We studied 72 children 7-14 years old (22 girls, 50 boys) mean age -- 10.8+/- 2.4 (SD), who were suffering from asthma. All children with forced expiratory volume in one second (FEV1) >70% of the predicted value and a reproducible fall in FEV1 after exercise of at least 15% were enrolled. After a screening test was performed the children were divided in 2 subgroups: 40 children for active treatment -- montelukast, 32 for placebo group. Placebo or montelukast (5 mg) was given once in the evening, randomised, double blind. Next day 3 bronchial provocation tests at 8 a.m., 12 a.m. and 3 p.m. were performed. Data from 72 patients were available for complete analysis of the following parameters: forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) forced expiratory flow at 25 and 75 of forced vital capacity (FEF 25-75%)., Results: Analysis showed a significant total protective effect 12 h after giving montelukast in 25/40 (62.5%) children, but only in 4/32 (12.5%) in the placebo group, (OR=1.87). Partial protection was detected in 3/40 (7.5%) children in montelukast group and in 1/32 (3.3%) child in placebo group. Lack of protection was observed in 12/40 (30%) in montelukast group and in 27/42 (84.4%) in the placebo group., Conclusions: l. The clinically recommended dose of montelukast protects against post exercise induced bronchospasm. 2. The time of duration of montelukast as protective treatment of post exercise bronchospasm was at least 21 hours. 3. Our study may suggest the participation of leukotrienes in the pathogenesis of exercise-induced broncho-constriction.

Background: One of the main stimuli that cause asthma exacerbations in children is physical activity, and exercise-induced bronchospasm (EIB) occurs in most asthmatic patients., Objective: To investigate the level of preparedness for a potential EIB event in suburban children involved in recreational sports., Methods: A cross-sectional study, focusing on children 12 years and younger, who participated in Little League baseball or soccer in Lower Merion Township, PA, was conducted by clinical survey. The survey was performed during a face-to-face encounter with the parent or caretaker of the child., Results: Five hundred seventy-nine children 12 years and younger were surveyed. The parents or caretakers of 80 reported a history of asthma, indicating a prevalence of 14%. Only 18 (22%) of these children with asthma were reported to have a rescue medicine readily available. The 95% confidence interval was 14.22% to 33.47%, indicating that we can be 95% certain that the true population with rescue medication lies between 14% and 33%., Conclusions: Despite having been diagnosed as having asthma, more than 75% of children surveyed were unprepared for an EIB event. Measures should be explored to improve the quality of care of asthmatic children involved in community sports. We also propose that it may be beneficial for first-aid kits to include a beta2-agonist bronchodilator.

This review assesses the evidence on the efficacy of leukotriene antagonists in the management of exercise-induced bronchospasm (EIB) in children. Only two randomized, double-blind, placebo-controlled, crossover studies have examined the effect of leukotriene antagonists in EIB in a pediatric setting. All other studies, including those comparing leukotriene antagonists with other agents such as beta(2)-adrenoceptor agonists (beta(2)-agonists) and inhaled corticosteroids, primarily involve adult patients. In children, not receiving other asthma medication, leukotriene antagonists can offer statistically significant protection from EIB compared with placebo. However, protection is not complete, as a significant proportion of children will continue to experience a >15% reduction in FEV(1). None of the studies involved children treated concurrently with other asthma medications; therefore, comments on additive therapy cannot be made. Despite evidence from only a few studies, leukotriene antagonists are seen to be well tolerated, efficacious, and of benefit to some children. In addition, current management for EIB with short-acting beta(2)-agonists is less than ideal. It is therefore concluded that in children with EIB, leukotriene antagonists are indicated on a trial basis with individualized therapy and follow-up to evaluate treatment response.

Objective: Physical activity is an important and frequent trigger of airways obstruction in asthmatic children. We aimed to compare the efficacies of 50 microg salmeterol twice daily and 2 mg SCG four times daily with respect to protection from exercise induced bronchoconstriction (EIB)., Methods: Twenty seven children and adolescents aged 4 to 16 years with mild or moderate exercise induced asthma (FEV1 70% to 90% predicted) were admitted to the study. Exercise challenge was performed on a treadmill using a predefined protocol in order to produce 10 minutes of exercise at near-maximum targets. The trial had a randomised, cross-over design comprising a 3-day run-in period and two 7-day treatment periods, separated by a one-week washout period., Results: The mean protective efficacy of salmeterol was larger than that of SCG. A difference between treatments of 39.7% (95% CI, - 0,8 to 68.9%) in favour of salmeterol was calculated using a Hodges-Lehmann-estimate. The maximum post-challenge fall in FEV subset 1 was significantly lower (p<0.001) after salmeterol than after SCG (- 5.6 +/- 6.4% vs. -12.1 +/- 9.3%, respectively). In addition, salmeterol improved base-line lung function to a greater degree than SCG. FEV1 increased by 0.4 l/sec after salmeterol, whereas no improvement was observed after SCG., Conclusions: A one-week treatment with salmeterol 50 microg b.i.d in asthmatic children and adolescents provided better protection against EIB and improved baseline lung function as compared to SCG four times daily.

Exercise-induced bronchospasm is an obstruction of transient airflow that usually occurs five to 15 minutes after physical exertion. Although this condition is highly preventable, it is still underrecognized and affects aerobic fitness and quality of life. Diagnosis is based on the results of a detailed history, including assessment of asthma triggers, symptoms suggestive of exercise-induced bronchoconstriction, and a normal forced expiratory volume at one second at rest. A trial of therapy with an inhaled beta agonist may be instituted, with the subsequent addition of inhaled anti-inflammatory agents or ipratropium bromide. Nonpharmacologic measures, such as increased physical conditioning, warm-up exercises, and covering the mouth and nose, should be instituted. If symptoms persist, pulmonary function testing is warranted to rule out underlying lung disease.

Background: Exercise-induced bronchoconstriction (EIB) following strenuous physical exertion afflicts many people. It can be the cause of sub-optimal performance, symptoms such as cough, dyspnea, wheeze and chest tightness, and can lead people to avoid physical activity. Management of EIB focuses on prevention through pharmaco-therapy and alternate strategies. Single use, pre-exercise, beta-agonists and non-steroidal antiinflammatory agents are recommended., Objectives: Bronchodilator medications have been commonly used to prevent narrowing of airways after exercise, but anti-inflammatory drugs such as nedocromil sodium have also been used. The objective of this review was to assess the effects of a single dose of nedocromil sodium to prevent exercise-induced bronchoconstriction., Search Strategy: 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., Selection Criteria: Randomised trials comparing a single dose of nedocromil sodium with placebo to prevent exercise-induced bronchoconstriction in patients with EIB over six years of age., Data Collection and Analysis: Trial quality assessment and data extraction were conducted independently by two reviewers. Study authors were contacted for confirmation of data., Main Results: The combined results from 20 randomised controlled trials involving 280 participants, show that 4 mg, of nedocromil sodium inhaled 15 to 60 minutes prior to exercise significantly reduce the severity and duration of EIB in both adults and children, when compared to placebo. The maximum percentage fall in FEV1 was improved significantly compared to placebo (weighted mean difference 15.5 %; 95% confidence interval:13.2 to 18.1). For the maximum percentage fall in peak expiratory flow rate (PEFR) the improvement was similar: WMD 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. It had a greater effect on those 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 with the short term use of nedocromil. A further search conducted in September 2001 did not yield any further studies., Reviewer's Conclusions: Nedocromil sodium used before exercise reduces the severity and duration of exercise-induced bronchoconstriction. This effect appears to be more pronounced in people with severe exercise-induced bronchoconstriction.

Background: Montelukast is a specific antagonist of leukotrienes' receptors and constitutes a therapeutic option in controlling asthma., Objectives: To evaluate efficacy of montelukast in patients with persistent light asthma, persistent moderate asthma and exercise-induced asthma; to try to reduce or to eliminate doses of inhaled steroid; to reduce the use of short-action beta agonists and to assess its tolerability in pediatric patients., Material and Method: 40 patients were studied, 17 female, with an age range from 4 to 11 years and a mean of 7 years. Stratification was made by GINA-established parameters., Results: Steroid dose could be reduced in 88%, with definitive suspension in 66% of patients. Moreover, an improvement in reducing asthma stratification and the use of rescue drugs were registered. 62% of patients with exercise-induced asthma improved and there was a good tolerance with the same side effects.

A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8-16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7-14 days. After inhalation, airway caliber (FEV(1)) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV(1)). A significant increase in FEV(1) was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV(1) from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV(1) after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P = 0.038 and AUC 92.0%.min vs. 205.7%.min, respectively, P = 0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children., (Copyright 2001 Wiley-Liss, Inc.)

Background: Previous studies in which leukotriene-receptor antagonist and corticosteroids were used have suggested a possible role for these anti-inflammatory drugs in the prevention of exercise-induced bronchoconstriction, but no direct comparisons have been made., Objective: A crossover study was undertaken to compare the ability of both montelukast and budesonide to protect patients from exercise-induced bronchoconstriction., Methods: A total of 20 patients (median age, 17 years; range, 8 to 36 years), who had clinical exercise-induced bronchoconstriction for 1 year and decreased FEV1 of at least 20% after exercise on two occasions, were enrolled in this study. To compare the therapies in each patient, we administered, consecutively, 10 mg of montelukast once daily at bedtime for 3 days and, later, 400 microg of budesonide twice daily for 15 days, or vice versa, with a 15-day intervening washout period during which no patient received treatment. Exercise challenges were performed at baseline (no therapy) and after each treatment. The percentage of FEV1 declines at 2, 7, and 12 minutes after exercise and the area under the curve (summarizing the extent and modification of FEV1 decreases relative to time) were measured and compared., Results: Both budesonide and montelukast significantly reduced the decrease in FEV1 (area under the curve) after exercise with respect to the baseline condition of no therapy (P = 0.0001). Overall, budesonide offered better protection (area under the curve) than did montelukast (P = 0.01), particularly in the short-term evaluation (2 minutes after exercise; P = 0.003); however, considerable individual variations in the responses to both budesonide and montelukast were observed. The degree of protection against decreases in FEV1 ranged from 0% to almost 100% for both treatments. In 16 of 20 patients, budesonide therapy offered better protection than did montelukast, and in the other 4 patients, montelukast showed better protection than did budesonide. No side effects of either montelukast or budesonide were detected during the study., Conclusions: Treatment with budesonide or montelukast prevents exercise-induced bronchoconstriction. Because substantial variation in the response may be present among patients, both drugs should be tested in each patient before long-term therapy is chosen.

Leukotriene receptor antagonists (LTRA) are a new class of drugs for asthma treatment, available in tablet form. Their unique mechanism of action results in a combination of both bronchodilator and anti-inflammatory effects. While their optimal place in asthma management is still under review, LTRA represent an important advance in asthma pharmacotherapy.

Exercise is a common stimulus of bronchoconstriction in subjects with asthma. Exercise-induced asthma (EIA) may be caused by heat loss and/or water loss during exercise. These changes cause the release of mediators and the development of bronchoconstriction. Recent studies have implicated the cysteinyl leukotrienes in the pathogenesis of EIA. Therefore we investigated the effect of a leukotriene antagonist, pranlukast hydrate, on EIA. Subjects were 11 EIA positive patients and were all atopic type bronchial asthma. 450 mg of pranlukast hydrate was given for 14 days and the exercise test was performed before and after treatment. Pulmonary function tests were done before and 0, 5, 15 and 30 min after completion of the each exercise. Prostaglandin E2, thromboxane B2, leukotriene E4 and B4 in urine were measured before and after the treatment. Pranlukast hydrate did not affect FEV1.0, PF and Flow volume curve at rest and also levels of mediators in urine. The mean maximal percentage fall in FEV1.0 after exercise was--54.9 +/- 5.7% without therapy and--30.1 +/- 7.5% after pranlukast hydrate therapy. There was a significant difference between FEV1.0 values before and treatment at each time (p < 0.05). This study demonstrated that pretreatment with a potent and selective leukotriene antagonist, pranlukast hydrate, attenuated EIA, and it suggests that leukotriene plays a role in EIA.

When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment., (Copyright 2000 Wiley-Liss, Inc.)

Background: Nedocromil sodium and sodium cromoglycate inhaled shortly before exercise appear to reduce the severity of exercise-induced bronchoconstriction. There is some debate over which drug may be more effective., Objectives: The objective of this review was to compare the effects on post-exercise lung function between prophylactic doses of nedocromil sodium (NSG) and sodium cromoglycate (SCG) in persons diagnosed with exercise-induced bronchoconstriction., Search Strategy: Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register which compiles searches of CINAHL, EMBASE, MEDLINE and CENTRAL, plus hand searches for trials in 20 journals. Bibliographies of relevant studies and review articles were searched and primary authors, content experts and manufacturers of drugs were contacted for additional relevant studies. No language restrictions were applied., Selection Criteria: Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were included if: the participants, aged 6 or over, had a confirmed diagnosis of asthma with exercise-induced bronchoconstriction, were subjected to an exercise challenge sufficient to trigger bronchoconstriction, and the measures of lung function were reported as either changes in forced expiratory volume in one second or peak expiratory flow rate., Data Collection and Analysis: Data extraction and methodological quality assessments were conducted independently by two reviewers using standard forms and validated assessment criteria. In some cases results were extrapolated from graphs. Results from similar studies were pooled and reported as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CI) using the random effects model., Main Results: Of the 92 citations retrieved from the original search, a total of 8 studies were included in this review (117 participants). No significant difference was noted between NCS and SCG with respect to the maximum percent decrease in FEV1 (WMD = -0.88; 95% CI: -4.50, 2.74), complete protection (i.e. maximum % fall FEV1 still =>10%); OR = 0.95; 95% CI: 0.50 to 1.8, clinical protection (i.e. < 50% improvement over placebo); OR = 0.71; 95% CI: 0.36 to 1.39; unpleasant taste (OR = 6.85; 95% CI: 0.77, 60.73), or sore throat (OR = 3.46; 95% CI: 0.32, 37.48). For these pooled comparisons, no statistically significant heterogeneity was identified. Subgroup analyses based on age, dosage of medications and timing of exercise post-inhalation were consistent with the overall pooled analyses., Reviewer's Conclusions: No significant differences were evident between the effect of NCS and SCG during the immediate post-exercise period in adults and children with EIB with regards to pulmonary function - specifically maximum percent decrease in FEV1, complete protection, clinical protection, or side effects.

Leukotrienes have been shown to cause bronchoconstriction, increased mucus production, and airway inflammation, three critical features in asthma. Antileukotriene drugs were developed to inhibit the effects of these lipid mediators. This class of drugs represents the first new approach to asthma therapy in 25 years. The leukotriene receptor antagonists, montelukast, zafirlukast, and pranlukast, and the 5-lipoxygenase inhibitor, zileuton, are unique in their ability to target specific components of asthmatic inflammation. Although the role of these drugs continues to evolve, the antileukotrienes have demonstrated efficacy against exercise and allergen-induced bronchoconstriction and additive benefit for use in patients with symptomatic, moderate asthma on maintenance-inhaled corticosteroids. Further, they may be considered for primary use in patients with mild, persistent asthma, especially those who are steroid-phobic or who have compliance issues.

Elucidation of the biochemistry of leukotriene production and the pharmacology of its actions has led to the development of a number of therapeutic agents shown to be of value in the treatment of asthma. These agents either prevent the synthesis of the leukotrienes, by preventing the action of the 5-lipoxygenase-activating protein or the catalytic action of the 5-lipoxygenase, or by inhibiting the action of leukotrienes at the CysLT1 receptor. Numerous clinical trials in exercise-induced asthma, allergen-induced asthma, aspirin-induced asthma, and spontaneously occurring asthmatic episodes have indicated that these agents are safe and effective asthma treatments.

Exercise-induced bronchospasm, exercise-induced bronchoconstriction, and exercise-induced asthma (EIA) are all terms used to describe the phenomenon of transient airflow obstruction associated with physical exertion. It is a prominent finding in children and young adults because of their greater participation in vigorous activities. The symptoms shortness of breath, cough, chest tightness, and wheezing normally follow the brief period of bronchodilation present early in the course of exercise. Bronchospasm typically arises within 10 to 15 minutes of beginning exercise, peaks 8 to 15 minutes after the exertion is concluded, and resolves about 60 minutes later, but it also may appear during sustained exertion. EIA occurs in up to 90% of asthmatics and 40% of patients with allergic rhinitis; among athletes and in the general population its prevalence is between 6% and 13%. EIA frequently goes undiagnosed. Approximately 9% of individuals with EIA have no history of asthma or allergy. Fifty percent of children with asthma who gave a negative history for EIA had a positive response to exercise challenge.6 Among high school athletes, 12% of subjects not considered to be at risk by history or baseline spirometry tested positive. Before the 1984 Olympic games, of 597 members of the US team, 67 (11%) were found to have EIA. Remarkably, only 26 had been previously identified, emphasizing the importance of screening for EIA even in well-conditioned individuals who appear to be in excellent health. The severity of bronchospasm in EIA is related to the level of ventilation, to heat and water loss from the respiratory tree, and also to the rate of airway rewarming and rehydration after the challenge. Postexercise decrease in the peak expiratory flow rate of normal children may be as much as 15%; therefore, only a decrease in excess of 15% should be viewed as diagnostic. EIA is usually provoked by a workload sufficient to produce 80% of maximum oxygen consumption; however, in severe asthmatics even minimal exertion may be enough to produce symptoms. Patients with normal lung function at rest may have severe air flow limitation induced by exercise,10 and as many as 50% of patients who are well-controlled with inhaled corticosteroids still exhibit EIA. A challenge of sufficient magnitude will provoke EIA in all patients with asthma. PHARMACOLOGIC THERAPY: Exercise, unlike exposure to allergens, does not produce a long-term increase in airway reactivity. Accordingly, patients whose symptoms manifest only after strenuous activity may be treated prophylactically and do not require continuous therapy. Most asthma medications, even some unconventional ones such as heparin, furosemide, calcium channel blockers, and terfenadine, given before exercise, suppress EIA. McFadden accounts for the efficacy of these disparate classes of drugs by their potential effect on the bronchial vasculature that modulates the cooling and/or rewarming phases of the reaction. Short-acting -agonists provide protection in 80% to 95% of affected individuals with insignificant side effects and have been regarded for many years as first-line therapy. Two long-acting bronchodilators, salmeterol and formoterol, have been found effective in the prevention of EIA.18-21 A single 50-microg dose of salmeterol protects against EIA for 9 hours; its duration appears to wane in the course of daily therapy. Cromolyn sodium is highly effective in 70% to 87% of those diagnosed with EIA and has minimal side effects. Nedocromil sodium provides protection equal to that of cromolyn in children. Children commonly engage in unplanned physical activity and sometimes are not allowed to carry their own medication. Thus, a simple long-acting regimen given at home is likely to be more effective than short-acting drugs that must be administered in a timely manner. Although the 12-hour protection by salmeterol reported by Bronsky et al may not persist with continued use, the 9-hour duration of action is