montelukast and Asthma--Exercise-Induced

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.. 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.. 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.. 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.. The evidence suggests that montelukast is an effective monotherapy controller in children with mild asthma.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Bronchoconstriction; Child; Child, Preschool; Cyclopropanes; Glucocorticoids; Humans; Hypersensitivity, Immediate; Leukotriene Antagonists; Patient Compliance; Quinolines; Randomized Controlled Trials as Topic; Sulfides

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.

Topics: Acetates; Administration, Oral; Adolescent; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Child; Child, Preschool; Cyclopropanes; Humans; Leukotriene Antagonists; Meta-Analysis as Topic; Molecular Structure; Quinolines; Sulfides

Leukotriene inhibitors are the first new class of medications for the treatment of persistent asthma that have been approved by the U.S. Food and Drug Administration in more than two decades. They also have been approved for the treatment of allergic rhinitis. Prescriptions of leukotriene inhibitors have outpaced the evidence supporting their use, perhaps because of perceived ease of use compared with other asthma medications. In the treatment of persistent asthma, randomized controlled trials have shown leukotriene inhibitors to be more effective than placebo but less effective than inhaled corticosteroids. The use of leukotriene inhibitors has not consistently shown an inhaled-steroid-sparing effect, a reduction in need for systemic steroid treatment, or a cost savings. For exercise-induced asthma, leukotriene inhibitors are as effective as long-acting beta2-agonist bronchodilators and are superior to placebo; they have not been compared with short-acting bronchodilators. Leukotriene inhibitors are as effective as antihistamines but are less effective than intranasal steroids for the treatment of allergic rhinitis. The use of leukotriene inhibitors in treating atopic dermatitis, aspirin-intolerant asthma, and chronic idiopathic urticaria appears promising but has not been studied thoroughly. Leukotriene inhibitors have minimal side effects and are well tolerated in most populations.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Cyclopropanes; Dermatitis, Atopic; Humans; Hydroxyurea; Hypersensitivity; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sulfides; Sulfonamides; Tosyl Compounds

Montelukast sodium (Singulair, Merck and Co., Inc., Whitehouse Station, NJ) is a selective and orally-active leukotriene receptor antagonist with demonstrated effectiveness for treating allergic asthma and allergic rhinitis in adults and children as young as 12 months of age for allergic asthma and 6 months of age for allergic rhinitis. It was recently approved in the US for prevention of exercise-induced bronchoconstriction in patients who are > or = 15 years of age. This paper updates a prior review of the data on the clinical efficacy of montelukast published in this journal.

Topics: Acetates; Animals; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Bronchoconstriction; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sulfides

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate. Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.

Topics: Acetates; Administration, Inhalation; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Economics, Pharmaceutical; Ethanolamines; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Quinolines; Salmeterol Xinafoate; Sulfides; Therapeutic Equivalency

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.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Chronic Disease; Cyclopropanes; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Sulfides; Sulfonamides; Tosyl Compounds

The three leukotriene (LT) modifiers approved for use in the United States, zileuton, zafirlukast, and montelukast, are the first new class of therapeutic agents to be introduced in 20 years for the treatment of asthma. These agents are referred to as leukotriene modifiers and have clearly demonstrated the ability to ameliorate bronchoconstriction and indices of airway edema and abnormal mucus production as observed in clinical trials. These agents have been shown to improve airflow, reduce the need for an inhaled bronchodilator, and improve nocturnal awakenings and asthma symptom scores appreciably. When combined with inhaled corticosteroid therapy, they may either provide additional improvement in efficacy or permit the reduction of the dose of inhaled corticosteroid necessary for effective therapy. Physicians should be familiar with these agents and consider them for use in their practice, in conjunction with current asthma management guidelines.

Topics: Acetates; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Asthma, Exercise-Induced; Cyclopropanes; Drug Evaluation; Humans; Hydroxyurea; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Sulfides; Sulfonamides; Tosyl Compounds; Treatment Outcome

Topics: Acetates; Adult; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Child; Cyclopropanes; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Randomized Controlled Trials as Topic; Sulfides; Sulfonamides; Tosyl Compounds

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Budesonide; Child; Cyclopropanes; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukotriene Antagonists; Male; Placebos; Quinolines; Receptors, Leukotriene; Signal Transduction; Sulfides

Montelukast has been proven to assure a protective effect against exercise-induced bronchoconstriction.. To verify exactly when montelukast begins protection in asthmatic children by evaluating different time intervals between dosing and challenge.. In a double blind, placebo-controlled, three day doses, crossover study, patients were randomized to receive in sequence treatment with either a placebo or montelukast and assigned to one of seven groups that were tested 1, 2, 3, 4, 5, 6 and 8 h after drug administration, respectively. For each group, the exercise challenge was always performed at the same hour on the first and third days of treatment.. Sixty-nine asthmatic children took part in the study. On day 3, the mean FEV(1) % fall from baseline was 25.54 (95% CI = 21.63/29.46) and 14.89 (95% CI = 11.85/17.92) for the placebo and active drug (p < 0.05), respectively. On day 1, the mean fall of FEV(1) was 28.20 (95% CI = 24.46/31.94) and 19.01 (95% CI = 15.71/22.31) for the placebo and montelukast (p < 0.05), respectively. Clinical protection was achieved in 21 (30%) and 33 (48%) subjects by montelukast on the first and third days, respectively.. Montelukast assured protection against exercise-induced bronchoconstriction from the first through the eighth hour from the first day of treatment. However, individual susceptibility to protection was evident since some individuals were not protected at any time. We conclude that in clinical use individual responses to the drug should be carefully evaluated in the follow-up management.

Topics: Acetates; Asthma, Exercise-Induced; Bronchoconstriction; Child; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Exercise Test; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides; Time Factors

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.. 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.. 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.. 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.

Topics: Acetates; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchoconstriction; Bronchodilator Agents; Child; Cromolyn Sodium; Cyclopropanes; Ethanolamines; Exercise; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Mannitol; Middle Aged; Nitric Oxide; Quinolines; Respiratory Sounds; Sulfides; Young Adult

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.. 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.. 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).. 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.

Topics: Acetates; Adolescent; Adult; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Placebo Effect; Quinolines; Sulfides; Young Adult

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

Topics: Acetates; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchoconstriction; Child; Cyclopropanes; Drug Resistance; Exercise Test; Female; Forced Expiratory Volume; Gene Frequency; Genotype; Humans; Immunoglobulin E; Interleukin-13; Korea; Leukotriene Antagonists; Male; Polymorphism, Single Nucleotide; Quinolines; Sulfides

The leukotriene inhibitor montelukast has been recommended against exercise-induced asthma (EIA), however, single-dose agents might be favourable in several aspects.. To compare the protective effects against EIA of a single inhalation of the combination disodium cromoglycate (DSCG, CAS 16110-51-3) and reproterol (REP, CAS 54063-54-6) with 3 days oral treatment of montelukast (MON, CAS 158966-92-8).. Open-label, cross-over, single-centre trial. Twenty-four 6 to 18-year-old children and adolescents, with reversible and stable airway obstruction, baseline FEV1 > or = 70%, predicted and proven EIA (i.e. a maximum decrease of FEV1 by > or = 20% compared with baseline) were treated with MON, orally for 3 days in the evening, or one single inhalation of DSCG/REP 20 min before the exercise challenge. The treatment sequence was randomised. The exercise test on a treadmill was performed under standardised conditions.. 24 patients completed both periods. Both treatments clearly provided protection against EIA; however, protection of DSCG/REP was more pronounced than that of MON. This difference was statistically significant even if the data were adjusted for the increase in FEV1 between inhalation of DSCG/REP and challenge (DSCG/REP(adjusted). The nadir FEV1 level after exercise following prophylaxis with DSCG/REP was even higher than the pre-inhalation FEV1 value. From these data, protection indices of 66%, 81%, and 113% for MON, DSCG/REP(adjusted), and DSCG/REP(unadjusted), respectively, were estimated.. Inhalation of DSCG/REP before exercise provides significantly better protection against EIA than three days treatment with MON.

Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchodilator Agents; Child, Preschool; Cromolyn Sodium; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Combinations; Exercise Test; Female; Forced Expiratory Flow Rates; Humans; Male; Metaproterenol; Quinolines; Sulfides; Theophylline

To compare pretreatment with albuterol versus montelukast added to the current asthma regimen for protection against exercise-induced bronchospasm in children with mild-to-moderate asthma, and to determine whether cysteinyl leukotriene (Cys-LT) concentrations measured in the exhaled breath condensate correlated with response to montelukast.. Prospective, randomized, double-blind, double-dummy, crossover study.. Asthma clinic at a university-affiliated medical center.. Eleven children aged 7-17 years with physician-diagnosed mild-to-moderate asthma for at least 6 months and with self-reported exercise-induced bronchospasm (defined as > or = 15% decrease in forced expiratory volume in 1 sec [FEV(1)] at screening and baseline visit).. Patients were randomly assigned to receive 3-7 days of oral montelukast 5-10 mg/day or 2 puffs of an albuterol metered-dose inhaler just before an exercise challenge and then were crossed over to the alternate therapy for the last visit.. Serial spirometry was performed before and at 0, 5, 10, 15, 30, 45, and 60 minutes after the exercise challenge at each visit. Measurement of exhaled breath condensate was performed at the screening visit and study visits 1 and 2. The primary outcome was the maximum change in FEV(1) after exercise. Secondary outcomes were the area under the curve for FEV(1) (expressed as percentage decrease from baseline) during the first 60 minutes (AUC(0-60)) after exercise and the proportion of patients in whom exercise-induced bronchospasm was prevented (defined as < 15% decrease in FEV(1) after exercise challenge). The mean +/- SD maximum decrease in FEV(1) was 27.5 +/- 7.9% at baseline. Patients receiving montelukast had an 18.3 +/- 13.7% decrease in FEV(1) compared with 0.7 +/- 1.6% in patients receiving albuterol (p=0.002, paired t test). Exercise-induced bronchospasm was prevented in 100% of the patients receiving albuterol compared with 55% receiving montelukast (p<0.05, McNemar's test). The AUC(0-60) was significantly smaller with albuterol compared with montelukast (p<0.001, Wilcoxon signed rank test). No correlations were found between Cys-LT concentration and the severity of exercise-induced bronchospasm or the response to montelukast.. Pretreatment with albuterol is more effective than montelukast for prevention of exercise-induced bronchospasm in children with asthma.

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Hospitals, University; Humans; Male; Prospective Studies; Quinolines; Spirometry; Sulfides

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.. 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.. 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.. 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.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Breath Tests; Bronchoconstriction; Bronchospirometry; Child; Cyclopropanes; Exercise Test; Exercise Therapy; Exhalation; Female; Humans; Italy; Male; Methacholine Chloride; Physical Fitness; Quinolines; Sulfides

The objective of this double-blind cross-over study was to evaluate montelukast for the prevention of exercise-induced bronchoconstriction (EIB). Sixty-two patients with EIB (post-exercise decrease in forced expiratory volume in 1 second (FEV(1)) > or = 20% at pre-randomization) were randomized to montelukast 10 mg or placebo, followed by exercise-challenge 2, 12, and 24 hours postdose. The primary endpoint was the maximum percent-fall in FEV(1) (from pre-exercise FEV(1)) during 60 minutes after exercise-challenge at 2 hours postdose. This endpoint was improved after montelukast (mean +/- SD = 11.7% +/- 10.8) versus placebo (17.5% +/- 13.8) (p < or = 0.001); numerically greater improvements were seen at 12 hours and 24 hours. A quicker time to recovery after challenge (p < or = 0.001) and a smaller area under the curve for percent-fall in FEV(1) during 60 minutes after challenge (p < or = 0.01) were seen with montelukast at 2 hours. At this timepoint, more patients taking montelukast (45/54) than taking placebo (37/54) were protected against EIB (p = 0.039). We concluded that montelukast provided significant protection against EIB at 2 hours after a single dose.

Topics: Acetates; Administration, Oral; Adolescent; Adult; Asthma, Exercise-Induced; Bronchoconstriction; Cross-Over Studies; Cyclopropanes; Exercise; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides; Time Factors

Montelukast is recommended to be taken in the evening. The effectiveness of this drug to prevent exercise-induced bronchoconstriction (EIB) in children was already evaluated. However, there is no information to determine if this effectiveness could vary depending on dosage time. Children (n = 24) with a documented history of EIB performed an exercise challenge test before starting montelukast treatment. Twelve children were randomly allocated to receive the drug in the morning for 2 weeks, and another 12 to receive it in the evening. After this treatment period and after a week of washout, the children were crossed over. An exercise test was repeated after the first and second periods of treatment. Values obtained after morning or evening dosage were compared with pretreatment values for the whole group of children. There was a significant effect of montelukast for protecting against EIB, measured both as percent of maximum fall in forced expired volume in 1 sec (FEV1) (18.9 +/- 9.7, morning, 18.7 +/- 11.3, evening, vs. 27.5 +/- 9.8, pretreatment; P < 0.05) or as area under the curve (156.4 +/- 102.0, morning, 145.4 +/- 130.6, evening, vs. 294.3 +/- 156.5, pretreatment; P < 0.005). There were no statistical differences between taking the drug in the morning or evening. In conclusion, montelukast, taken for 2 weeks, is equally effective in exercise-induced bronchoconstriction when dosing either in the morning or in the evening.

Topics: Acetates; Adolescent; Analysis of Variance; Area Under Curve; Asthma, Exercise-Induced; Bronchial Hyperreactivity; Bronchoconstriction; Child; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Probability; Prospective Studies; Quinolines; Risk Assessment; Severity of Illness Index; Sulfides; Treatment Outcome

The effect over time of regular treatment with montelukast (MNT) in inhibiting exercise-induced bronchoconstriction (EIB) has never been evaluated in children. The aim of the present study was to examine the preventive effect of MNT against EIB in children at different time-points over a 4-week treatment period. Thirty-two asthmatic children (aged 6-12 yrs) were enrolled in a double-blinded, randomised, parallel group design to receive a 4-week treatment with MNT (5 mg chewable tablets administered once daily in the evening) or placebo. Exercise challenge was performed at baseline and after 3, 7 and 28 days of treatment, 20-24 h after dosing. MNT was significantly more protective than placebo against EIB at each time. The mean percentage drop of forced expiratory volume in one second (FEV1) was 24.6, 13.6, 12.0 and 11.6 for MNT, and 24.4, 22.4, 21.8 and 21.0 for placebo, at baseline and after 3, 7 and 28 days, respectively. For each drug, no significant difference in the percentage drop of FEV1 was found between different days. Regular treatment with montelukast provided significant protection against exercise-induced bronchoconstriction in asthmatic children over a 4-week period with no tolerance to the bronchoprotective effect.

Topics: Acetates; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchoconstriction; Case-Control Studies; Child; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Quinolines; Sulfides

Leukotriene modifiers have been shown to protect against exercise-induced bronchoconstriction (EIB) with repeated, chronic dosing.. To study the onset and duration of protection against EIB after a single dose of montelukast, a leukotriene receptor antagonist.. In this randomized, crossover, double-blind study, 51 adult asthma patients with EIB (> or = 20% postexercise decrease in forced expiratory volume in 1 second [FEV1]) received a single oral dose of montelukast (10 mg), or placebo followed by exercise challenge 2, 12, and 24 hours after dosing. The primary end point was maximum percentage decrease in FEV1 from preexercise baseline during 60 minutes after the 2-hour challenge.. At 2, 12, and 24 hours after dosing, the maximum decrease in FEV1 was 10.8% +/- 7.9%, 8.4% +/- 7.5%, and 8.3% +/- 7.3% for montelukast and 22.3% +/- 13.1%, 16.1% +/- 10.2%, and 16.9% +/- 11.7% for placebo, respectively (P < or = .001 at each time point). Postexercise recovery was quicker with montelukast than with placebo (P < or = .001); mean (95% confidence interval) differences were -26.8 minutes (-35.1 to -18.4 minutes), -16.0 minutes (-22.9 to -9.2 minutes), and -17.4 minutes (-24.9 to -9.9 minutes) at the 3 time points, respectively. At all time points, area under the curve for percentage decrease in FEV1 during 60 minutes after exercise was smaller after montelukast (P < or = .001); montelukast protected more patients against EIB (P < or = .001). Fewer patients required postexercise beta-agonist rescue at 2 hours after dosing with montelukast (P = .03).. Montelukast provided significant protection against EIB as soon as 2 hours after a single oral dose, with persistent benefit up to 24 hours.

Topics: Acetates; Administration, Oral; Adolescent; Adrenergic beta-Agonists; Adult; Area Under Curve; Asthma, Exercise-Induced; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Exercise Test; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sulfides; Time Factors

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.. To examine the effectiveness of montelukast after exercise and after EVH.. 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.. 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.. 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.

Topics: Acetates; Adolescent; Adult; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchoconstriction; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Exercise; Exercise Test; Female; Forced Expiratory Volume; Humans; Hyperventilation; Leukotriene Antagonists; Male; Quinolines; Sulfides; Temperature; Treatment Outcome; Vital Capacity

Controlled clinical trials on the effects of leukotriene antagonists on asthma-like symptoms, bronchial hyperresponsiveness and airway inflammation have not been performed in elite athletes.. In 2001, we examined 88 of 102 (86%) players from three junior, national league ice hockey teams in Helsinki. Athletes were included in the intervention if they reported at least two exercise-induced bronchial symptoms (wheeze, cough, shortness of breath) weekly during the previous month on a previously validated respiratory-symptom questionnaire. Sixteen male ice hockey players fulfilled the study criteria. A double-blind, randomized, cross-over, placebo-controlled study included 4-week active treatment (10 mg oral montelukast, bedtime), 1-week washout period, and 4-week placebo treatment. Before entering the study, all patients were clinically examined, skin prick tested, filled in a respiratory symptom questionnaire, performed a spirometry and a histamine challenge test, and gave induced sputum samples. Exhaled NO was measured. These measures were repeated after both treatment periods. During the treatment the athletes kept daily diary on lower respiratory tract symptoms on a scale from 0 (no symptoms) to 10 (most severe symptoms), morning peak expiratory flow (PEF), training amount, and use of study medication. Primary end-point was daily lower respiratory tract symptom score.. Montelukast had no effect on daily lower respiratory symptom scores, spirometry parameters [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, PEF], bronchial hyperresponsiveness, sputum eosinophil or neutrophil cell counts, exhaled NO measurements, or morning PEF. Nine subjects were atopic in skin prick test, but their results did not differ from the nonatopic subjects.. A leukotriene antagonist, montelukast, was of no benefit in the treatment of asthma-like symptoms, increased bronchial hyperresponsiveness or a mixed type of eosinophilic and neutrophilic airway inflammation in highly-trained ice hockey players.

Topics: Acetates; Administration, Oral; Adult; Analysis of Variance; Asthma, Exercise-Induced; Bronchial Hyperreactivity; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Finland; Hockey; Humans; Leukotriene Antagonists; Male; Probability; Quinolines; Reference Values; Risk Assessment; Severity of Illness Index; Spirometry; Statistics, Nonparametric; Sulfides; Treatment Failure

To compare the effect of montelukast and the long-acting beta(2)-agonist salmeterol on cardiopulmonary exercise economy and physical performance in adult patients with asthma during exercise.. Asthmatic patients (n = 18), aged 18 to 35 years with exercise-induced bronchoconstriction (EIB), using a double-blind, double-dummy cross-over design. Montelukast, 10 mg/d, was compared to inhaled salmeterol, 50 microg bid. The study medication was administered for at least 5 days prior to testing, with a washout period of at least 5 days. Treadmill exercise tests (5.3% inclination, -15 degrees C ambient temperature) were performed at work loads of 80% of maximal oxygen uptake (Vo(2)max) [6 min], rest (4 min), 60% of Vo(2)max (6 min), and finally step increments until exhaustion.. We investigated parameters of gas exchange, physical performance, and lung function. After montelukast, the oxygen pulse was higher than after salmeterol, at 80% of Vo(2)max (p = 0.035), and 6 min at 60% of Vo(2)max (p = 0.011). Lung function during exercise, running time to exhaustion, Borg score, lactate levels, Vo(2)max, carbon dioxide elimination, minute ventilation, ventilatory equivalents, respiratory exchange ratio, and heart rate were not significantly different between the two treatments. The maximal postexercise fall in FEV(1) from baseline occurred 2 min after run to exhaustion, and was greater after salmeterol than after montelukast: mean, 16.2% (SD, 11.0) vs 10.0% (SD, 12.2) [p < 0.001].. In adult asthmatics with EIB, montelukast may have a more favorable effect on the oxygen pulse, thus suggesting improved gas exchange during exercise.

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchoconstriction; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Lactates; Male; Pulmonary Gas Exchange; Quinolines; Salmeterol Xinafoate; Sulfides

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.. 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.. 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.. 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.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchodilator Agents; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Fluticasone; Forced Expiratory Volume; Humans; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Outcome

The aim of the study was to evaluate the protective effect of single-dose, combination treatment comprising montelukast (5 mg) and loratadine (10 mg), on exercise-induced bronchoconstriction in asthmatic children. The combination was compared to placebo, loratadine and montelukast alone. Nineteen children were enrolled in a double-blind randomised, single-dose, crossover study. For each treatment patients undertook two treadmill exercise tests, 2 and 12 h respectively after single-dose administration. No significant differences were seen in the maximum fall in forced expiratory volume in one second (FEV1) 2 h after treatment and placebo. Whereas significant differences in maximum fall in FEV1 were observed between treatment groups 12 h after administration. Loratadine alone did not show any significant protection or any additional effect in comparison with montelukast alone. Single doses of montelukast and montelukast plus loratadine were significantly more effective than loratadine at 12 h. The present study, performed using single-dose treatments, demonstrated that maximal protective effect by montelukast was obtained 12 h after dosing and that montelukast plus loratadine did not result in significant additive bronchoprotective effects on exercise-induced bronchoconstriction.

Topics: Acetates; Adolescent; Age Factors; Asthma; Asthma, Exercise-Induced; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Exercise Test; Female; Forced Expiratory Volume; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Loratadine; Male; Quinolines; Sulfides

Leukotriene antagonists are effective in the treatment of exercise-induced bronchoconstriction. Montelukast is a specific cysteinyl-leukotriene receptor1 antagonist without known effects on the pulmonary vessels, which in theory should be advantageous with respect to gas exchange. In addition to lung function, we investigated the effects of montelukast on parameters of gas exchange and physical performance in 16 asthmatics with exercise-induced bronchoconstriction in a double-blind cross-over placebo-controlled study. Subjects were tested at an ambient temperature of -15 degrees C with a tread mill exercise protocol consisting of consecutive workloads of 80% V'O(2max) (6 min), rest (4 min), 60% V'O(2max) (6 min) and step increments of exercise until exhaustion. Montelukast reduced the maximum post-exercise fall in FEV1 (P < 0.01), improved the running time to exhaustion in 11 of 16 test subjects (one unchanged) (P = 0.03), and reduced the Borg score at exhaustion (P = 0.03) and the breathing frequency after 3 min at 60% V'O(2max) (P = 0.03). V'(O2), V'CO(2), minute ventilation, ventilatory equivalents, respiratory exchange ratio, heart rate and oxygen pulse were not significantly different after montelukast and placebo. We conclude that montelukast has a beneficial effect on physical performance in most adults with exercise-induced asthma without any observed effect on gas-exchange parameters.

Topics: Acetates; Adult; Analysis of Variance; Asthma, Exercise-Induced; Bronchial Provocation Tests; Bronchoconstriction; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Pulmonary Gas Exchange; Quinolines; Respiration; Spirometry; Statistics, Nonparametric; Sulfides

Montelukast, a cysteinyl-leukotriene receptor antagonist, was reported to have a protective effect against exercise-induced bronchoconstriction (EIB). Aspirin-induced asthma (AIA) is characterized by overproduction of cysteinyl-leukotrienes.. The aim of the study was to compare the response to exercise and the effect of montelukast on EIB in AIA as compared to aspirin-tolerant asthma (ATA).. A placebo-controlled, double blind, cross-over randomized study was performed in 19 AIA and 21 ATA patients with stable asthma. A single dose of montelukast (10 mg) or placebo (PL), was given orally one hour prior to exercise challenge. FEV1 was measured before and 5, 10, 15 min after exercise and then at 15-minute intervals for 4 h. Urinary LTE4 excretion and blood eosinophil count were measured at baseline, 2 h and 4 h following exercise challenge.. Positive bronchial response to exercise was observed in 47.5% of all patients studied. Exercise led to almost identical maximal fall in FEV1 in AIA and ATA patients (23.5% +/- 6.8% vs. 21.8% +/- 12.0%, respectively; P = 0.7). Montelukast, as compared to PL, significantly attenuated EIB in 63.2% of 19 patients with positive exercise test preceded by PL. The mean of maximum fall in FEV1 from the pre-exercise value was 10.2% +/- 13.8 after montelukast as compared to 22.5% +/- 10.2 after placebo (P < 0.001). No significant differences between protective effect of montelukast was observed in AIA as compared to ATA patients (P = 0.63, anova). Urinary LTE4 excretion showed no change following exercise, irrespective of the result of the test in all subjects.. Patients with AIA and ATA react similarly to exercise challenge and obtain similar protection against EIB by montelukast.

Topics: Acetates; Adult; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma, Exercise-Induced; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Hypersensitivity; Exercise Test; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Leukotriene E4; Lung; Male; Middle Aged; Quinolines; Sulfides

The aim of this study was to evaluate the timing of onset and the duration of action of a single oral-dose treatment with montelukast in comparison to placebo on exercise-induced asthma (EIA) in asthmatic children. Nineteen children (7-13 years) with stable asthma were evaluated. Patients undertook three consecutive treadmill exercise tests, respectively, 2, 12 and 24 h after a single-dose administration. A double-blind randomized, single-dose, placebo-controlled, crossover design was used. To assess bronchoconstriction after the exercise challenge, the maximal percentage fall in FEV1 (DeltaFEV1) from the baseline value was considered. Two hours after dosing, DeltaFEV1 was -15.33 +/- 2.93 for placebo and -13.33 +/- 2.03 for montelukast. At 12 h, DeltaFEV1 was -18.69 +/- 2.83 for placebo, -9.78 +/- 1.85 for montelukast (p < 0.005). No difference was observed between placebo (DeltaFEV1-10.21 +/- 2.07) and montelukast (DeltaFEV1-9.10 +/- 2.02) at 24 h. Analysis of the degree of protection showed a significant efficacy of montelukast (p = 0.02) in comparison with placebo only at 12 h. Montelukast showed a significant protective effect 12 h after dosing, but no effect after 2 and 24 h. In mild asthmatics, the timing of administration of single dosage before exercise should be strictly considered in order to obtain the drug protective effects.

Topics: Acetates; Adolescent; Asthma, Exercise-Induced; Child; Child Welfare; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Exercise Test; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides; Time Factors; Treatment Outcome

Montelukast, an oral, once-daily leukotriene receptor antagonist, provides protection against exercise-induced bronchoconstriction.. To evaluate the effect of 8 weeks of therapy with salmeterol aerosol or montelukast on exercise-induced bronchoconstriction in adults with asthma.. 8-week multicenter, randomized, double-blind study.. 17 asthma treatment centers in the United States.. 191 adults with asthma who had documented exercise-induced bronchoconstriction.. Qualified patients were randomly assigned to double-blind treatment with montelukast (10 mg once in the evening) or salmeterol (50 microg [2 puffs] twice daily).. Changes in pre-exercise and postexercise challenge values; percentage inhibition in the maximal percentage decrease in FEV1; the area above the FEV1-time curve; and time to recovery of FEV1 at days 1 to 3, week 4, and week 8 of treatment.. By day 3, similar and statistically significant reductions in maximal percentage decrease in FEV1 were seen with both therapies. Sustained improvement occurred in the montelukast group at weeks 4 and 8; at these time points, the bronchoprotective effect of salmeterol decreased significantly. At week 8, the percentage inhibition in the maximal percentage decrease in FEV1 was 57.2% in the montelukast group and 33.0% in the salmeterol group (P = 0.002). By week 8, 67% of patients receiving montelukast and 46% of patients receiving salmeterol had a maximal percentage decrease in FEV1 of less than 20%.. The bronchoprotective effect of montelukast was maintained throughout 8 weeks of study. In contrast, significant loss of bronchoprotection at weeks 4 and 8 was seen with salmeterol. Long-term administration of montelukast provided consistent inhibition of exercise-induced bronchoconstriction at the end of the 8-week dosing interval without tolerance.

Topics: Acetates; Administration, Oral; Adolescent; Adult; Albuterol; Area Under Curve; Asthma, Exercise-Induced; Bronchoconstriction; Bronchodilator Agents; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides

Montelukast, a leukotriene receptor antagonist, and salmeterol, a long-acting beta(2)-receptor agonist, each have demonstrated benefits in the treatment of exercise-induced bronchoconstriction (EIB) in short-term studies. Direct comparisons between these agents in long-term studies are limited.. We sought to compare montelukast and salmeterol in the long-term treatment of EIB.. One hundred ninety-seven patients with mild asthma and a postexercise fall in FEV(1) of at least 18% were randomized (double-blind) to receive montelukast 10 mg once daily or salmeterol 50 microg twice daily for 8 weeks. Exercise challenge was repeated at day 3, week 4, and week 8 after randomization near the end of the dosing interval for both drugs. The primary efficacy endpoint was the maximal percent fall in postexercise FEV(1) at week 8.. Montelukast was effective in treating EIB without inducing tolerance and provided superior (P

Topics: Acetates; Adolescent; Adult; Albuterol; Asthma, Exercise-Induced; Bronchial Diseases; Bronchodilator Agents; Constriction, Pathologic; Cyclopropanes; Double-Blind Method; Female; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Single-Blind Method; Sulfides

Patients with mild asthma frequently have only exercise-induced bronchoconstriction, a symptom of inadequate control of asthma. We evaluated the ability of montelukast, a leukotriene-receptor antagonist, to protect such patients against exercise-induced bronchoconstriction.. We randomly assigned 110 patients (age, 15 to 45 years) with mild asthma and a decrease in the forced expiratory volume in one second (FEV1) of at least 20 percent after exercise on two occasions during a placebo run-in period to receive 10 mg of montelukast (54 patients) or placebo (56 patients) once daily at bedtime for 12 weeks in a double-blind study. Treatment was followed by a two-week, single-blind washout period during which all patients received placebo. Exercise challenges were performed at base line; 20 to 24 hours after dosing at weeks 4, 8, and 12; and at the end of the washout period. The primary end point was the area under the curve for FEV1 (expressed as the percent change from base-line values) in the first 60 minutes after exercise. This measure summarized the extent and duration of bronchoconstriction after exercise.. At 12 weeks, montelukast therapy offered significantly greater protection against exercise-induced bronchoconstriction than placebo therapy (expressed as the percentage of inhibition of the end points), as evidenced by the improvement in the area under the FEV1 curve (degree of inhibition, 47.4 percent; P=0.002). Montelukast therapy was also associated with a significant improvement in the maximal decrease in FEV1 after exercise (P=0.003) and the time from the maximal decrease in FEV1 to the return of lung function to within 5 percent of pre-exercise values (P=0.04). The differences between groups in the various measures of lung function were similar at 4, 8, and 12 weeks; there was no evidence of rebound worsening of lung function in the montelukast group after the washout period. After 12 weeks of treatment, patients in the montelukast group were more likely to rate their asthma control as better and less likely to require rescue therapy with a beta-agonist during or after exercise challenge. The rates of adverse events were similar in the two groups.. As compared with placebo, once-daily treatment with montelukast provided significant protection against exercise-induced asthma over a 12-week period. Tolerance to the medication and rebound worsening of lung function after discontinuation of treatment were not seen.

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchial Provocation Tests; Bronchoconstriction; Cyclopropanes; Double-Blind Method; Exercise; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Methacholine Chloride; Middle Aged; Quinolines; Sulfides

A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction was also investigated.. Nineteen non-smoking asthmatic patients with a forced expiratory volume in one second (FEV1) of > or = 65% of the predicted value and a reproducible fall in FEV1 after exercise of at least 20% were enrolled. Subjects received placebo and montelukast 100 mg once daily in the evening or 50 mg twice daily, each for two days, in a three-period, randomised, double blind, crossover design. In the evening, approximately 20-24 hours after the once daily dose or 12 hours after the twice daily dose, a standardised exercise challenge was performed. Data from 14 patients were available for complete analysis.. The mean (SD) maximal percentage decrease in FEV1 after exercise was 29.6 (16.0), 17.1 (8.2), and 14.0 (9.4) for placebo, once daily, and twice daily regimens, respectively. The mean (95% CI) percentage protection was 37 (15 to 59) for the group who received 50 mg twice daily and 50 (31 to 69) for those who received 100 mg once daily. Active treatments were not different from each other. The mean (SD) plasma concentrations of montelukast were higher after the twice daily regimen (1.27 (0.81) microgram/ml) than after the once daily regimen (0.12 (0.09) microgram/ml); there was no correlation between the percentage protection against exercise-induced bronchoconstriction and plasma concentrations. After exercise urinary excretion of LTE4 increased significantly during placebo treatment (from 34.3 to 73.7 pg/mg creatinine; p < 0.05) but did not correlate with the extent of exercise-induced bronchoconstriction.. Montelukast protects similarly against exercise-induced bronchoconstriction between plasma concentrations of 0.12 and 1.27 micrograms/ml. The increase in the urinary excretion of LTE4 after exercise and the protection from exercise-induced bronchoconstriction with a cysteinyl leukotriene receptor antagonist provide further evidence of the role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

Topics: Acetates; Adolescent; Adult; Asthma, Exercise-Induced; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Exercise; Exercise Test; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Leukotriene E4; Male; Middle Aged; Quinolines; Sulfides

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.. 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.

Topics: Acetates; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Sulfides

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.. 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).. 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).. 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.

Topics: Acetates; Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Drug Administration Schedule; Exercise Test; Female; Forced Expiratory Volume; Humans; Male; Mannitol; Quinolines; Sulfides; Treatment Outcome; Young Adult

Topics: Acetates; Adolescent; Adverse Drug Reaction Reporting Systems; Asthma, Exercise-Induced; Child; Cyclopropanes; Drug-Related Side Effects and Adverse Reactions; Humans; Hypersensitivity; Male; Quinolines; Research Report; Sulfides

As previous studies have shown that cysteinyl leukotrienes are important mediators in exercise-induced bronchoconstriction (EIB), and leukotriene receptor antagonists (LTRAs) such as montelukast have been shown to improve post-exercise bronchoconstrictor responses, we herein investigated whether clinical responsiveness to montelukast was associated with polymorphisms in the genes encoding leukotriene C4 synthase (LTC4S) and cysteinyl leukotriene receptor 1 (CysLTR1) and/or clinical parameters in Korean asthmatic children with EIB.. The study population consisted of 100 asthmatic children with EIB. The individuals studied were given exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks. Responders were defined as children showing>10% post-treatment improvement in forced expiratory volume in 1 s (FEV1). The LTC4S A(-444)C and CysLTR1 T(+927)C polymorphisms were genotyped by PCR-restriction fragment length polymorphism analysis.. Of 100 enrolled children, 68 were classified as responders and 32 were classified as non-responders. No significant association was observed between montelukast responsiveness and LTC4S or CysLTR1 genotype, either alone or in combination. In contrast, montelukast-induced improvement in FEV(1) after exercise was correlated with higher pre-treatment PC20 (methacholine) values (r=0.210, P=0.036) and lower total IgE levels (r=-0.216, P=0.031).. The LTC4S A(-444)C and CysLTR1 T(+927)C genotypes do not appear to be useful for predicting clinical responsiveness to montelukast, whereas bronchial hyperresponsiveness and total IgE appear to predict the degree of montelukast responsiveness in Korean asthmatic children with EIB.

Topics: Acetates; Asthma, Exercise-Induced; Bronchial Hyperreactivity; Child; Cyclopropanes; Drug Resistance; Female; Glutathione Transferase; Humans; Immunoglobulin E; Korea; Leukotriene Antagonists; Male; Membrane Proteins; Polymorphism, Genetic; Prognosis; Quinolines; Receptors, Leukotriene; Sulfides; Treatment Outcome

It is recognized that airway inflammation has a central role in the pathogenesis of asthma, but how it relates to exercise-induced bronchoconstriction (EIB) is not completely understood.. The aim of our study was to investigate the relationship between EIB and baseline concentrations of cysteinyl leukotrienes (Cys-LTs) and other inflammatory markers in exhaled breath condensate (EBC).. EBC was collected, and the fraction of exhaled nitric oxide (FE NO ) was measured in a group of 19 asthmatic children, after which they performed a treadmill exercise test. Fourteen healthy children were enrolled as control subjects.. The asthmatic children were divided into the EIB group (decrease in FEV 1 , > or =12%) and the non-EIB group. The EBC was analyzed for the presence of Cys-LTs, leukotriene B 4 , and ammonia. Asthmatic patients with EIB (mean FEV 1 decrease, 23% +/- 3%) had higher Cys-LT concentrations than either asthmatic patients without EIB or control subjects (42.2 pg/mL [median] vs 11.7 pg/mL and 5.8 pg/mL; P < .05 and P < .001, respectively). Ammonia concentrations were lower in both the EIB and non-EIB groups than in control subjects (253.2 microM and 334.6 microM vs 798.4 microM; P < .01 and P < .05, respectively). No difference in EBC leukotriene B 4 levels was found among the 3 groups. Both asthmatic groups had higher FE NO levels than control subjects ( P < .001). EBC Cys-LT ( P < .01; r = 0.7) and FE NO ( P < .05; r = 0.5) values both correlated significantly with the postexercise FEV 1 decrease.. this study shows that EBC Cys-LT values are higher in asthmatic children with EIB and correlate with the decrease in FEV 1 after exercise. These findings suggest that the pathways of both Cys-LT and nitric oxide are involved in the pathogenesis of EIB.

Topics: Acetates; Adolescent; Ammonia; Asthma, Exercise-Induced; Biomarkers; Breath Tests; Bronchoconstriction; Child; Cyclopropanes; Cysteine; Exhalation; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Leukotriene B4; Leukotrienes; Nitric Oxide; Quinolines; Respiratory Function Tests; Sulfides

To study the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist, in the treatment and prevention of exercise-induced bronchoconstriction (EIB) in mild asthmatic patients and patients with exercise-induced asthma (EIA).. Thirty mild asthmatic patients with positive standardized exercise challenge test were enrolled. The subjects received montelukast 10 mg once daily in the evening. Standard exercise challenge was performed before, three days and twenty-eight days after the administration of the drug. The end points included: (1) Area under the percent fall in forced expiratory volume in one second (FEV1) versus time curve (AUC0 to approximately 60 min); (2) Time of recovery to within 5% of the pre-exercise baseline FEV1 value; and (3) Maximal percent fall in FEV1 from pre-exercise baseline.. Montelukast caused significant reduction in AUC0 to approximately 60 min, which was (39 +/- 21)%.min before treatment as compared to (13 +/- 14)%.min and (12 +/- 14)%.min three days and twenty-eight days respectively after the treatment with montelukast. Time of recovery to within 5% of the pre-exercise baseline FEV1 value were (51 +/- 36) min, (26 +/- 28) min and (25 +/- 33) min respectively. The mean maximal percentage decrease in FEV1 after exercise was 44.4% before treatment, 26.8% and 18.2% following montelukast. FEV1 and peak expiratory flow rate (PEFR) were maintained to nearly normal during all the study. Inhale corticosteroid did not prevent EIB/EIA.. Montelukast attenuates and protects against EIB/EIA.

Topics: Acetates; Adolescent; Adult; Asthma, Exercise-Induced; Bronchial Provocation Tests; Bronchoconstriction; Cyclopropanes; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Respiratory Function Tests; Sulfides

Topics: Acetates; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Child; Combined Modality Therapy; Cyclopropanes; Humans; Physical Education and Training; Quinolines; Sulfides

Topics: Acetates; Adolescent; Albuterol; Asthma, Exercise-Induced; Child; Cyclopropanes; Drug Administration Schedule; Humans; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Outcome

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.. A crossover study was undertaken to compare the ability of both montelukast and budesonide to protect patients from exercise-induced bronchoconstriction.. 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.. 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.. 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.

Topics: Acetates; Adolescent; Adult; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchoconstriction; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Female; Forced Expiratory Volume; Humans; Male; Quinolines; Spirometry; Sulfides

Topics: Acetates; Adolescent; Asthma, Exercise-Induced; Child; Cyclopropanes; Humans; Physical Fitness; Quinolines; Sports; Sulfides

During the past decade, the inflammatory mechanisms that result in the clinical syndrome we call asthma have been emphasized in research, publications, and the various asthma management guidelines. This information clearly emphasizes the treatment of asthma with maintenance controller therapies early after the onset of symptoms in all but the very mildest of patients. Until the advent of the leukotriene receptor antagonists, nearly all of these maintenance therapies needed to be administered by inhalation through a variety of devices and spacers. Inhalation of medication was necessary to either increase the amount of drug reaching the airways or to increase the therapeutic index of drugs such as corticosteroids. Even under the best circumstances, this route of administration is difficult and expensive for many parents whose children have asthma. Now that oral controller therapies (leukotriene receptor antagonists) are available for children, their role in clinical practice needs to be examined. The latest asthma management guidelines classify asthma into four groups of severity, and base treatment recommendations on the intensity of symptoms, need for rescue medications, and pulmonary function as measured by peak expiratory flow and forced expiratory volume in 1 sec (FEV(1)). The categories of mild intermittent, mild persistent, moderate persistent, and severe asthma in children will be addressed in this presentation by reviewing the available data on the use of the leukotriene receptor antagonist montelukast in children. Mild intermittent asthma can be typified by exercise-induced asthma, a common pediatric condition. In this often troublesome condition, montelukast demonstrated effectiveness at the end of a once a day dose by blocking the effects of this naturally occurring challenge. Drug regulatory approval of a new drug also includes patients with more regular symptoms who are usually classified as having persistent or moderate asthma. In these montelukast pediatric studies, approximately 40% of patients were already taking inhaled corticosteroids. Patients had improvements in FEV(1), symptoms, and rescue medication use, clearly showing an effect with once a day dosing. Pediatric data in severe asthma patients are more limited, but in such patients a therapeutic trial of montelukast would seem preferable to using systemic corticosteroids or increasing inhaled steroids to a level where adverse effects have an increasing potential of occurring. Montelu

Topics: Acetates; Administration, Oral; Asthma; Asthma, Exercise-Induced; Child; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Respiratory Function Tests; Severity of Illness Index; Sulfides

Topics: Acetates; Albuterol; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchodilator Agents; Cyclopropanes; Ethics, Medical; Humans; Quinolines; Salmeterol Xinafoate; Sulfides

Topics: Acetates; Aged; Albuterol; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchodilator Agents; Chemical and Drug Induced Liver Injury; Cyclopropanes; Female; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Salmeterol Xinafoate; Sulfides; Sulfonamides; Tosyl Compounds

Topics: Acetates; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Bronchoconstriction; Cyclopropanes; Drug Tolerance; Humans; Leukotriene Antagonists; Quinolines; Salmeterol Xinafoate; Sulfides

Topics: Acetates; Albuterol; Asthma, Exercise-Induced; Bronchodilator Agents; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Salmeterol Xinafoate; Sulfides

Topics: Acetates; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Cyclopropanes; Double-Blind Method; Humans; Leukotriene Antagonists; Middle Aged; Multicenter Studies as Topic; Quinolines; Randomized Controlled Trials as Topic; Reproducibility of Results; Sulfides; Treatment Outcome

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Child; Cyclopropanes; Forced Expiratory Volume; Humans; Quinolines; Sulfides

Topics: Acetates; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Area Under Curve; Asthma, Exercise-Induced; Cold Temperature; Cyclopropanes; Forced Expiratory Volume; Humans; Humidity; Quinolines; Salmeterol Xinafoate; Sulfides