Exercise-induced bronchoconstriction, allergy and sports in children.

Exercise-induced bronchoconstriction (EIB) is characterized by the narrowing of airways during or after physical activity, leading to symptoms such as wheezing, coughing, and shortness of breath. Distinguishing between EIB and exercise-induced asthma (EIA) is essential, given their divergent therapeutic and prognostic considerations. EIB has been increasingly recognized as a significant concern in pediatric athletes. Moreover, studies indicate a noteworthy prevalence of EIB in children with atopic predispositions, unveiling a potential link between allergic sensitivities and exercise-induced respiratory symptoms, underpinned by an inflammatory reaction caused by mechanical, environmental, and genetic factors. Holistic management of EIB in children necessitates a correct diagnosis and a combination of pharmacological and non-pharmacological interventions. This review delves into the latest evidence concerning EIB in the pediatric population, exploring its associations with atopy and sports, and emphasizing the appropriate diagnostic and therapeutic approaches by highlighting various clinical scenarios.

Management of Exercise-Induced Bronchoconstriction in Athletes.

Exercise-induced bronchoconstriction (EIB) is a phenomenon observed in asthma but is also seen in healthy individuals and frequently in athletes. High prevalence rates are observed in athletes engaged in endurance sports, winter sports, and swimming. The pathophysiology of EIB is thought to be related to hyperventilation, cold air, and epithelial damage caused by chlorine and fine particles in inspired air. Several diagnostic procedures can be used; however, the diagnosis of EIB based on self-reported symptoms is not reliable and requires an objective examination. The hyperosmolar inhalation test and eucapnic voluntary hyperpnea test, which involve indirect stimulation of the airway, are useful for the diagnosis of EIB. A short-acting ß-agonist is the first choice for prevention of EIB, and an inhaled corticosteroid is essential for patients with asthma. Furthermore, treatment should accommodate antidoping requirements in elite athletes. Tailoring of the therapeutic strategy to the individual case and the prognosis after cessation of athletic activity are issues that should be clarified in the future.

The Effect of Aerosolized Chlorpheniramine Maleate on Exercise Induced Bronchospasm and Gas Exchange in Asthmatics.

INTRODUCTION: Exercise induced asthma (EIB) is an acute, reversible, usually selflimiting airways obstruction which sets in after exercise in patients with asthma. One popular mechanism of EIA is the increase in histamine and its metabolites in circulation after exercise, which leads to bronchoconstriction via histamine receptors in bronchi. Chlorpheniramine Maleate is potent, less sedative antihistaminic drug, which acts by inhibiting histamine release from mast cells. It is also said to have anticholinergic properties. The aerosol route of administration of a drug has the advantages of a faster onset of action, fewer side effects, and greater protection against EIB with respect to small airways function. This study was conducted to evaluate the effect of Chlorpheniramine Maleate aerosol inhalation on flow volumes and gas exchange. MATERIALS AND METHODS: 25 established patients of stabilized bronchial asthma (18 to 44 years) with history of EIA attending Allergy OPD, Medical OPD or Chest clinic were included in the present study. Patients were studied for 3 days in a week at the same time of day. Baseline spirometry was done to know test parameters, i.e. FEV1, PEFR and FEF50%. Gas exchange study during rest including minute ventilation (VE), oxygen consumption (VO2), Carbon dioxide produced per minute (VCO2), Respiratory quotient (R) was carried out. Patient was asked to perform exercise on bicycle ergometer. During exercise VE, VO2, VCO2 and R were recorded every 30 seconds. FEV1, PEFR and FEF50% were recorded immediately after and 5 min after completion of exercise. On day 2, same procedure was repeated with saline nebulisation before the exercise. On day 3, aerosolized Chlorpheniramine Maleate was used instead of saline for nebulisation. Values obtained were tabulated and analysed. OBSERVATIONS AND RESULTS: After exercise FEV1, PEFR, FEF50% decreased on all three days, but the fall in these parameters was less on Day III (prior nebulisation with Chlorpheniramine maleate) compared to previous days. There was significant increase in FEV1, PEFR and FEF50% (P<0.01, 0.05 and 0.05 respectively) which was seen 30 mins after inhalation of Chlorpheniramine maleate aerosol compared to placebo. Resting and exercise values of Minute Ventilation (VE), oxygen uptake (VO2) carbon dioxide expired, on all the three days were comparable and statistically not significant by the end of exercise. On day 2 and 3, 'R' as compared to that of day1 was slightly significant during rest and initial minutes of exercise but became insignificant after that till the end of exercise. CONCLUSION: This study shows that Chlorpheniramine causes bronchodilation during resting period by acting on the circulating or tissue histamine in asthmatics which contributes to an increase in resting bronchomotor tone. As there is incomplete inhibition of EIA by Chlorpheniramine, there may be some other associated mediator release for pathogenesis of EIA.

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

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

Exercise-induced laryngeal obstruction: Quality initiative to improve assessment and management.

INTRODUCTION: Exercise-induced laryngeal obstruction (EILO) affects 2-3% of the general population and 5.1% of elite athletes. Symptoms arise during high-intensity exercise and resolve at rest. EILO is often misdiagnosed as exercise-induced asthma as both conditions can present with dyspnea, chest tightness and cough. The purpose of this quality initiative was to identify patient characteristics that predict a higher likelihood of EILO, streamline referrals for exercise-endoscopy testing and avoid unnecessary medications. METHODS: A retrospective chart review included patients referred to a pediatric tertiary center between 2013 and 2018 for suspected EILO requesting exercise endoscopy. Data was collected from the patient chart and referral letters included age, sex, physical activity, medications, symptoms, and results of pulmonary and cardiac function tests. RESULTS: Between 2013 and 2018, 35 patients (9 males and 26 females, aged 5-18 years) were referred. Only 18 patients developed symptoms during an exercise endoscopy test. The majority were female (15/18), older than 10 years (18/18) and were involved in competitive sports (16/18). Stridor was the most common complaint among all patients referred (24/35) and many reported anxiety and high stress (15/35). The majority (63%) were previously treated with asthma medication. Pulmonary and cardiac function testing was not predictive of EILO. CONCLUSION: EILO is typically present in adolescent females involved in competitive sports. Anxiety and high stress was commonly noted. The majority were treated with asthma medication even though pulmonary function testing was normal. Recognition of this patient profile should improve timely access to appropriate diagnostic assessments, avoid unnecessary medical treatment, and promote a return to optimal athletic performance.

Small airway function in children with mild to moderate asthmatic symptoms.

BACKGROUND: Clinical significance of small airway obstruction in mild pediatric asthma is unclear. OBJECTIVE: To evaluate small airway properties in children with mild to moderate asthmatic symptoms and the association of small airway function with asthma control and exercise-induced bronchoconstriction (EIB). METHODS: Children (5-10 years old) with recurrent wheezing (n = 42) or persistent troublesome cough (n = 16) and healthy controls (n = 19) performed impulse oscillometry (IOS), spirometry, and a multiple-breath nitrogen washout (MBNW) test. Exhaled nitric oxide (NO) was measured at multiple flow rates to determine alveolar NO concentration (Calv). Asthma control was evaluated with the Childhood Asthma Control Test (C-ACT), short-acting ß2-agonist (SABA) use within the past month, and asthma exacerbations within the past year. RESULTS: IOS, spirometry, and exhaled NO indexes that are related to small airway function differed between children with recurrent wheezing and healthy controls, whereas only forced expiratory flow at 25% to 75% of the forced vital capacity was associated with persistent cough. The MBNW indexes showed no difference between the groups. Among symptomatic children, conducting airway ventilation inhomogeneity and Calv were associated with asthma exacerbations (P = .03 and P = .002, respectively), and lung clearance index and Calv were associated with EIB (P = .04 and P = .004, respectively). None of the proposed small airway indexes was associated with the C-ACT score or SABA use. CONCLUSION: Subtle changes were observed in the proposed small airway indexes of IOS, spirometry, and exhaled NO among children with mild to moderate recurrent wheezing. Small airway dysfunction, expressed as ventilation inhomogeneity indexes and Calv, was also associated with asthma exacerbations and EIB.

Exercise-Induced Bronchoconstriction: Background, Prevalence, and Sport Considerations.

The transient airway narrowing that occurs as a result of exercise is defined as exercise-induced bronchoconstriction (EIB). The prevalence of EIB has been reported to be up to 90% in asthmatic patients, reflecting the level of disease control. However, EIB may develop even in subjects without clinical asthma, particularly in children, athletes, patients with atopy or rhinitis, and following respiratory infections. The intensity, duration, and type of training have been associated with the occurrence of EIB. In athletes, EIB seems to be only partly reversible, and exercise seems to be a causative factor of airway inflammation and symptoms.

Pharmacologic Strategies for Exercise-Induced Bronchospasm with a Focus on Athletes.

Exercise-induced bronchoconstriction (EIB) is the transient narrowing of the airways during and after exercise that occurs in response to increased ventilation in susceptible individuals. It occurs across the age spectrum in patients with underlying asthma and can occur in athletes without baseline asthma. The inflammatory mechanisms underlying EIB in patients without asthma may be distinct from those underlying EIB in patients with asthma. This review summarizes mechanistic and clinical data that can guide the choice of chronic and acute pharmacologic therapies targeting control of EIB. Relevant regulations from the World Anti-Doping Agency are also discussed.

Notes on Test and Estimation in Comparison of Three Treatments under A Simple Carry-Over Three-Period Model.

Under the three-treatment three-period crossover design with simple carry-over effects, we derive the least-squares estimators for period effects, treatment effects and carry-over effects, as well as their covariance matrix in closed and explicit expressions. Using Monte Carlo simulation, we compare the test procedure adjusting carry-over with that ignoring carry-over with respect to Type I error and power. We further compare interval estimators adjusting carry-over with those ignoring carry-over with respect to the coverage probability and the average length. When the variation of responses within patients is small, the test procedure and interval estimators ignoring carry-over can lose accuracy in the presence of carry-over effects. When the variation of responses within patients is large, this loss of accuracy may become small or even minimal. We note that the loss of efficiency due to the adjustment of carry-over under the simple carry-over three-period crossover design is moderate, and is much less than that found for a two-period crossover design. We use the double-blind three-period crossover trial comparing formoterol solution aerosol and salbutamol suspension aerosol with a placebo for patients suffering from exercise-induced asthma on the forced expiratory volume in one second (FEV1) to illustrate the use of test procedures and interval estimators discussed here.

Mechanisms, measurement and management of exertional dyspnoea in asthma: Number 5 in the Series "Exertional dyspnoea" Edited by Pierantonio Laveneziana and Piergiuseppe Agostoni.

Asthma is a heterogeneous condition, with dyspnoea during exercise affecting individuals to a variable degree. This narrative review explores the mechanisms and measurement of exertional dyspnoea in asthma and summarises the available evidence for the efficacy of various interventions on exertional dyspnoea. Studies on the mechanisms of dyspnoea in asthma have largely utilised direct bronchoprovocation challenges, rather than exercise, which may invoke different physiological mechanisms. Thus, the description of dyspnoea during methacholine challenge can differ from what is experienced during daily activities, including exercise. Dyspnoea perception during exercise is influenced by many interacting variables, such as asthma severity and phenotype, bronchoconstriction, dynamic hyperinflation, respiratory drive and psychological factors. In addition to the intensity of dyspnoea, the qualitative description of dyspnoea may give important clues as to the underlying mechanism and may be an important endpoint for future interventional studies. There is currently little evidence demonstrating whether pharmacological or non-pharmacological interventions specifically improve exertional dyspnoea, which is an important area for future research.

Asthma and exercise-induced respiratory symptoms in the athlete: new insights.

PURPOSE OF REVIEW: Asthma and exercise-induced bronchoconstriction (EIB) are common in the athlete and can interfere with sport performances. In this review, we report recent findings on the prevalence, diagnosis and evaluation of these conditions, in addition to specific issues regarding their treatment and antidoping regulations. RECENT FINDINGS: Recent studies confirmed the high prevalence of exercise-induced respiratory symptoms, asthma and EIB, in athletes and showed that these conditions are still underdiagnosed and undertreated. Recent studies highlight the suboptimal use of asthma medication in asthmatic and allergic athletes. Regarding the diagnosis and treatment, questions about the role and criteria for positivity of eucapnic voluntary hyperpnea test were raised. It was confirmed that there is a subgroup of athletes with poor response to asthma medication. Finally, regarding antidoping regulations, new methods and changes in criteria for urinary bronchodilator thresholds were suggested. SUMMARY: Recent publications confirm that exercise-induced respiratory symptoms, asthma and EIB are common in athletes but often unrecognized and not optimally or successfully treated. It was suggested that current criteria for diagnostic bronchoprovocation test responses could be reassessed, as well as antidoping criteria for ß2-agonists urinary levels. There is a need for more research on prevention of airways dysfunction in athletes, identification of different asthma phenotypes and the benefits of standard asthma medication in this population.

New insights into treatment of children with exercise-induced asthma symptoms.

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.

Serum tryptase level and inflammatory markers in exhaled breath condensate of children with exercise-induced symptoms.

BACKGROUND: The pathogenesis of exercise-induced bronchoconstriction (EIB) is poorly understood. OBJECTIVE: To evaluate the biomarkers concentration in exhaled breath condensate (EBC) in schoolchildren with postexercise symptoms. We also evaluated changes in fractional exhaled nitric oxide (FeNO) value and the serum tryptase level after exercise. METHODS: One hundred children with postexercise symptoms were included. Methacholine challenge testing (MCT) was performed at visit 2, and exercise challenge testing (ECT) was performed at visit 3. Before and after ECT serum tryptase levels and FeNO values were measured. EBC was collected after ECT from 10 randomly selected children from each group. The children were assigned to the following groups: ECT(+) MCT(+), ECT(+) MCT(-), ECT(-) MCT(+), ECT(-) MC(-). We measured the following molecules: eotaxin, interleukin (IL) 8, IL-1ra, IL-1 beta, IL-6, IL-1 alpha, IL-12(p40), IL-5, granulocyte-macrophage colony-stimulating factor, IL-7, IL-15, IL-4, IL-2, IL-10, tumor necrosis factor alpha, interferon gamma, IL-13, tumor necrosis factor beta, monocyte chemoattractant protein-1, IL-17A, macrophage inflammatory proteins-1 alpha, macrophage inflammatory proteins-1 beta, IL-12(p70), and regulated on activation, normal T-cell expressed and secreted by using a multiplex immunoassay. Prostaglandin E2 (PGE2), leukotriene B4, and cysteinyl leukotriene were analyzed by using separate enzyme-linked immunosorbent assay kits. RESULTS: In the MCT(+) group, a detectable level of IL4 in EBC and detectible levels of eicosanoids were seen in the ECT(+) group. We observed the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations in patients with detectable compared with patients without detectable levels of cytokines in EBC. We showed ECT-induced reduction in the tryptase level in patients with a nondetectable PGE2 level in EBC and an increase in tryptase levels in patients who had detectable levels of PGE2 in EBC. CONCLUSIONS: EBC was a useful method to estimate inflammation but only in children with symptoms and with EIB shown by a positive ECT. Children with a positive ECT had detectable levels of eicosanoids in EBC; the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations was observed. The results of above study confirm the role of mast cells and eicosanoids in the pathogenesis of EIB in children.

Montelukast, current indications and prospective future applications.

INTRODUCTION: Montelukast is recommended for the treatment of asthma, exercise -induced bronchospasm and allergic rhinitis. Several trials demonstrated potential therapeutic effects in other respiratory conditions, and different animal-model-based studies explored potential pharmacological actions in non-respiratory conditions. AREAS COVERED: Clinical investigations on the pharmacotherapeutic effects of montelukast, in addition to in-vivo studies on animal models of non-respiratory diseases. The data discussed in this review were mainly obtained from clinical randomized trials, real-life studies, and studies based on animal models as approve of concept. As a condition, all of the discussed articles were published in journals cited by Pubmed. Expert commentary: The current clinical data are in favor of montelukast use in the management of chronic asthma as an add-on or alternative therapy to the inhaled corticosteroids. Further clinical trials are required to confirm the effectiveness and feasibility of montelukast for the treatment of conditions other than the current clinical indications.

The athlete "out of breath".

Athletes often complain about breathing problems. This is a crucial issue due to potential implications not only on their general health, but also on their competing performance. Asthma and exercise-induced bronchoconstriction are prevalent conditions in elite athletes, which leads doctors to rely most of the times on asthma medication to treat athletes feeling "out of breath". However, there are several other conditions that may mimic asthma and cause dyspnea in athletes. Effective treatment of dyspnea requires appropriate identification and treatment of all disorders. Proper knowledge and accurate diagnosis of such entities is mandatory, since asthma medication is not effective in those conditions. Herein we review the most common differential diagnosis of dyspnea in athletes, and describe the diagnostic strategies in order to increase awareness and to improve doctor's confidence on dealing with these patients.

Increased postexercise lipoxin A4 levels in exhaled breath condensate in asthmatic children with exercise-induced bronchoconstriction

Background: Lipoxins could be potential modulators of inflammation in the lungs. To our knowledge, the role of exhaled breath condensate (EBC) lipoxin A4 (LXA4) in asthmatic children with exercise-induced bronchoconstriction (EIB) has not been investigated. Objective: The aim of our study was to determine the involvement of EBC LXA4 in EIB. Methods: Forty-five patients aged between 5 and 17 years were included in the study. Patients were divided into 2 groups: asthmatic children with a positive response to exercise (n=17) and asthmatic children with a negative response to exercise (n=28). Levels of LXA4 were determined in EBC before and immediately after the exercise challenge using ELISA. Results: EBC LXA4 levels were significantly increased immediately after exercise in asthmatic children with a positive response to the exercise challenge (P=.05). No significant differences were observed in children with a negative response to exercise (P>.05). There was an inverse correlation between LXA4 levels and the percent degree of reduction in forced expiratory volume in the first second (FEV1%) postexercise in children with a positive exercise challenge (P=.05, r=-0.50). No significant differences were observed in LXA4 levels between atopic and nonatopic asthmatics (P>.05, Mann-Whitney U test). Conclusions: Levels of EBC LXA4 increased immediately after exercise in asthmatic children with a positive exercise challenge response. We hypothesize that airway LXA4 levels increase to compensate bronchoconstriction and suppress acute inflammation, and that spontaneous bronchodilatation after EIB may be due to LXA4 (AU)

Introducción: Las lipoxinas pueden actuar potencialmente como inmunomoduladores de la actividad inflamatoria en el pulmón. A nuestro entender, el papel de la lipoxina A4 (LXA4), determinada en condensado de aire exhalado (EBC) en niños asmáticos con broncoconstricción inducida por el ejercicio (BEI) no ha sido previamente investigado. Objetivo: El objetivo de nuestro estudio fue determinar la implicación de la LXA4 determinada en EBC, en el broncoespasmo inducido por ejercicio. Métodos: Se incluyeron en el estudio un total de cuarenta y cinco pacientes de edades comprendidas entre 5 y 17 años. Los pacientes se dividieron en dos grupos: niños asmáticos con respuestas positivas (n = 17) y negativas (n = 28) a la provocación bronquial con ejercicio. Los niveles de LXA4 en EBC se determinaron inmediatamente antes y después de la provocación bronquial mediante un método ELISA. Resultados: Los niveles de LXA4 en EBC aumentaron significativamente tras la provocación con ejercicio en aquellos niños asmáticos con respuestas positivas en la provocación (p = 0,05). Sin embargo, no pudimos encontrar ninguna diferencia estadísticamente significativa en pacientes con respuesta negativa al ejercicio (p > 0,05). Hubo una correlación inversa entre el incremento de los niveles de LXA4 y el grado de reducción porcentual del volumen espiratorio forzado en un segundo (FEV1%) en los pacientes con respuesta positiva a la provocación (p = 0,05, r = -0,50). No se observaron diferencias significativas en los niveles de LXA4 entre asmáticos alérgicos y no alérgicos (p> 0,05, prueba de Mann-Whitney). Conclusiones: Los niveles de EBC LXA4 se incrementan inmediatamente después de la broncoconstricción inducida por el ejercicio en niños asmáticos. Se postula que los niveles de las vías respiratorias aumentan LXA4 para suprimir la inflamación aguda en la vía respiratoria, y podrían ser responsables de la inducción de broncodilatación espontánea que aparece tras el EIB (AU)

Novel albuterol multidose dry powder inhaler in patients with exercise-induced bronchoconstriction: A single-dose, double-blind, randomized, 2-way crossover study.

BACKGROUND: A novel, inhalation-driven, multidose dry powder inhaler (MDPI) was developed that eliminates the need to coordinate device actuation with inhalation as is required with conventional metered-dose inhalers. OBJECTIVE: To evaluate albuterol MDPI efficacy and safety in patients with exercise-induced bronchoconstriction (EIB). METHODS: This single-dose, double-blind, 2-way crossover study randomized adolescents and adults with EIB (≥20% fall from pre-exercise challenge FEV(1)) to treatment sequences of albuterol MDPI (180 µg [2 inhalations of 90 µg each])/placebo MDPI (n = 19) or the reverse sequence (n = 19). FEV(1) was measured 30 and 5 min predose, 30 min postdose (ie, 5 min before treadmill exercise challenge; baseline) and 5, 10, 15, 30, and 60 min after exercise challenge. The primary efficacy endpoint was maximum percentage fall from baseline in FEV(1) up to 60 min post-exercise challenge. RESULTS: Mean maximum percentage fall in FEV(1) within 60 min post-exercise challenge was 6.2 ± 1.4% for albuterol MDPI versus 22.4 ± 1.4% for placebo MDPI (between-treatment difference: -16.2%; 95% CI: -20.2% to -12.1%; P < 0.0001). A significantly higher percentage of albuterol MDPI-treated patients were protected against EIB (<10% maximum FEV(1) fall post-exercise challenge) versus placebo MDPI (84.2% vs 15.8%; P < 0.0001). Protection with albuterol MDPI was evident within 5 min and maintained through 30 min; recovery was complete for both groups at 60 min. Treatment with a single dose of albuterol MDPI was generally well tolerated. CONCLUSIONS: Albuterol MDPI provides clinically significant protection from EIB in adolescents and adults with EIB; no new safety issues were observed with short-term albuterol MDPI use. ClinicalTrials.gov identifier NCT01791972.