fluticasone and Asthma--Exercise-Induced

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Antagonists; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma, Exercise-Induced; Athletes; Bronchodilator Agents; Chemoprevention; Clinical Trials as Topic; Fluticasone; Humans; Tachyphylaxis

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Child; Child, Preschool; Delayed-Action Preparations; Drug Combinations; Fluticasone; Humans; Infant; Leukotriene Antagonists; Nebulizers and Vaporizers; Salmeterol Xinafoate; Severity of Illness Index; Theophylline

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

Exercise-induced bronchoconstriction (EIB) is defined as a transient narrowing of the airways induced by exercise. Repetitive measurements of spirometric parameters, such as FEV(1) and expiratory flows, and forced oscillation technique (FOT) measurements can be used to analyze the dynamics of EIB. A single high dose of fluticasone propionate (FP) protects against EIB. The aim of the study was to analyze the effect of FP on the dynamics of exercise-induced airway narrowing as measured with FOT and spirometry.. Twelve children performed an exercise challenge on 2 separate days, 4 hr after inhalation of 1 mg FP (pressurized metered dose inhaler) or a placebo. Before and after the exercise flow-volume loops as well as the FOT (frequency range: 4-32 Hz) were measured.. The FEV(1) , and FEF(50) fell significantly after exercise within groups; the peak fall in FEV(1) after FP was significantly smaller than after placebo (respectively, 19.3 ± 14.6% and 29.2 ± 14.8%, P = 0.03, 95% CI: 0.9-18.8%). The fall in FEV(1) and FEF(50) peaked 3 min after exercise and showed a subsequent partial recovery. The fall in the FEV(1) /FVC ratio showed a later peak fall (12 min after exercise). The resistance increased while the reactance decreased significantly after exercise. FP significantly decreased the maximal increase in Rrs(6) when compared to the placebo (respectively 176.5 ± 59.1% and 201.0 ± 63.8%, P = 0.05, 95% CI: 0.5-48.7%). The maximal decrease in Xrs(6) was not significantly affected by FP (P = 0.06).. Repetitive spirometric and FOT measurements after exercise show a rapid narrowing and steady recovery of the patency of the conducting airways, and indicate a delayed and prolonged recovery of the smaller airways. A single high dose of inhaled FP seems to employ its effect mainly in the conducting airways.

Topics: Administration, Inhalation; Adolescent; Airway Obstruction; Androstadienes; Asthma, Exercise-Induced; Bronchoconstriction; Bronchodilator Agents; Child; Cross-Over Studies; Female; Fluticasone; Humans; Male; Respiratory Function Tests

The role of mast cells in the airway response to exercise and the benefit of sodium cromoglycate (SCG) in athletes are unclear.. The purpose of this study was to clarify the role of mast cell mediators in the airway response to exercise in athletes and to investigate the effect of SCG.. Eleven athletes with exercise-induced bronchoconstriction (EIB+) and 11 without (EIB-) performed a eucapnic voluntary hyperpnea (EVH) test (a surrogate for exercise) 10 min after inhalation of a placebo or 40 mg of the mast cell stabilizing agent sodium cromoglycate. The urinary concentrations of 9a,11β-PGF2 (a metabolite of PGD2 and a marker of mast cell activation) and leukotriene E4 (LTE4) were measured by enzyme immunoassay 60 min before and for 90 min after the challenge.. In the EIB+ group, the maximum fall in forced expiratory volume in 1 s (FEV1) of 20.3% ± 3% on placebo was reduced to 11.5% ± 1.9% after SCG (P = 0.003). There was an increase in the urinary excretion of 9α,11β-PGF2 on the placebo day after EVH in both groups (P < 0.05) that was abolished by SCG. In the EIB+ group, there was also an increase of urinary LTE4 on the placebo day that was abolished by SCG, whereas the urinary excretion of LTE4 was inconsistent in the EIB- group.. The results support mast cell activation with release of bronchoconstrictive mediators after hyperpnea in athletes with and without EIB and inhibition by SCG. The degree of airway responsiveness to the specific mediator released is likely to determine whether or not bronchoconstriction will occur after EVH.

Topics: Adrenergic Agonists; Adult; Androstadienes; Asthma, Exercise-Induced; Athletes; Bronchodilator Agents; Cromolyn Sodium; Dinoprost; Exercise Test; Female; Fluticasone; Forced Expiratory Volume; Humans; Hyperventilation; Inflammation Mediators; Leukotriene E4; Male; Mast Cells; Young Adult

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 is a common trigger in children with persistent asthma and inhaled corticosteroids have been shown to effectively treat clinical manifestations of persistent asthma, including protection from decrements in lung function caused by exercise. The goal of this study was to evaluate the effectiveness of fluticasone propionate/salmeterol 100/50 mcg compared with fluticasone propionate 100 mcg for the prevention of airflow limitation triggered by standardized exercise challenge in pediatric and adolescent patients with persistent asthma.. Multicenter, randomized, double-blind, parallel group trial of 248 subjects with persistent asthma (age 4-17 years) randomized to receive fluticasone propionate/salmeterol (100/50 mcg twice daily) or fluticasone propionate alone (100 mcg twice daily) via Diskus for 4 weeks. Exercise challenge tests were performed during screening and approximately 8 hr after administration of the blinded study medication on Treatment Day 28.. After 4 weeks of therapy both treatments provided protection following exercise challenge. The protection estimated by the maximal fall in FEV(1) was significantly better for fluticasone propionate/salmeterol (9.5 +/- 0.8% [mean +/- SE]) compared with fluticasone propionate alone (12.7 +/- 1.1%, P = 0.021). Statistically significant differences were not observed for asthma rescue-free days and asthma symptom-free days.. Chronic dosing with fluticasone propionate/salmeterol in a single device provides superior protection compared with an inhaled corticosteroid alone in protecting against exercise-induced asthma in children with persistent asthma.

Topics: Administration, Inhalation; Adolescent; Albuterol; Androstadienes; Asthma, Exercise-Induced; Bronchodilator Agents; Child; Child, Preschool; Drug Combinations; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Salmeterol Xinafoate

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

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Child; Double-Blind Method; Drug Combinations; Exercise Test; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged

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

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

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma, Exercise-Induced; Child; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Treatment Outcome

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

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Bronchoconstriction; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Male; Methacholine Chloride

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Fluticasone; Humans; Male; Salmeterol Xinafoate