(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Asthma--Exercise-Induced

Topics: Albuterol; Asthma; Asthma, Exercise-Induced; Atropine Derivatives; Beclomethasone; Child; Cromolyn Sodium; Humans; Ipratropium; Male

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

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Beclomethasone; Bronchoconstriction; Child; Child, Preschool; Cross-Over Studies; Exercise Test; Female; Forced Expiratory Volume; Heart Rate; Humans; Male; Posture; Respiratory Function Tests; Spirometry

The aim of this study was to assess whether a single high dose of beclomethasone dipropionate (BDP) could blunt mast cell activation and bronchoconstriction after eucapnic voluntary hyperpnea (EVH).. In this model of exercise-induced bronchoconstriction (EIB), seven athletes with EIB and eight untrained subjects with mild asthma performed two EVH tests 5.5 h apart on the same day; the first challenge after inhalation of a placebo aerosol and the second 4 h after inhalation of BDP (1500 microg). Prechallenge and postchallenge pulmonary function and urinary excretion of the mast cell mediator 9alpha, 11beta-prostaglandin (PG) F2 were followed, as well as urinary excretion of the bronchoconstrictor leukotriene (LT) E4.. The EVH-induced bronchoconstriction was inhibited by BDP in both groups (P < 0.001): in athletes, mean +/- SEM percent fall in forced expiratory volume in 1 s was 22% +/- 4% after placebo versus 13% +/- 3% after BDP; in subjects with asthma, 23% +/- 4% after placebo versus 14 +/- 3% after BDP. This inhibition of airway response was associated with a significant reduction in the urinary excretion of 9alpha,11beta-PGF2 (P = 0.039) and LTE4 (P = 0.003) in both groups. Significant correlations were found between the percent fall in forced expiratory volume in 1 s and the increase in urinary excretion of both mediators 9alpha,11beta-PGF2 (r = 0.544, P = 0.002) and LTE4 (r = 0.380, P = 0.038) after EVH.. We conclude that a single dose of BDP has an acute protective effect on the bronchial response to hyperpnea in both untrained subjects with asthma and athletes with EIB. This effect was associated with decreased excretion of urinary mediators, suggesting that BDP blunted the mast cell activation.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma, Exercise-Induced; Beclomethasone; Dose-Response Relationship, Drug; Female; Humans; Hyperventilation; Male; Mast Cells; Young Adult

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

Topics: Administration, Inhalation; Adolescent; Aerosol Propellants; Aerosols; Analysis of Variance; Anti-Asthmatic Agents; Area Under Curve; Asthma, Exercise-Induced; Beclomethasone; Child; Child, Preschool; Cross-Over Studies; Denmark; Double-Blind Method; Exercise Test; Female; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Nitric Oxide; Respiratory Function Tests; Treatment Outcome

The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma, but tolerance may develop to its bronchoprotective effect. We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily, instead of the usual dose of 50 microg twice daily, in adolescents receiving regular glucocorticoid inhalations. Methods. In a randomized, double-blind, 2x28-day crossover study, we administered salmeterol (50 microg) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance. Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period. The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise.. Fourteen subjects with a mean age of 13.1 years completed the study. The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours. After the 28th consecutive daily dose of salmeterol, the bronchoprotective effect was significantly greater than that of placebo at 1 hour, but not at 9 hours.. We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours, but that this effect may wane during regular once-daily salmeterol treatment, despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Albuterol; Asthma, Exercise-Induced; Beclomethasone; Bronchodilator Agents; Child; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Salmeterol Xinafoate

The role of airway inflammation in the pathogenesis of asthma in childhood is uncertain. In the present study, 27 atopic and nonatopic children aged 7-9 yrs who had > or = 5 episodes of wheeze and symptoms of exercise-induced asthma (EIA) in the previous 12 months, performed a methacholine challenge and exercise test on separate days at monthly intervals. The subjects had not received oral or inhaled corticosteroids for 12 months prior to the study. The dose-response relationship to inhaled methacholine was expressed as the cumulative dose provoking a 20% decrease in forced expiratory volume in one second (PD20). Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were measured prior to the exercise test and at 0, 3, 5, 10, 15 and 20 min following maximal exercise. Following the first methacholine challenge and exercise test, the children were randomized in a double-blind manner to receive inhaled beclomethasone dipropionate (BDP) 200 micrograms b.i.d. or a placebo b.i.d. from a Diskhaler for 3 months. All children were asymptomatic at the time of testing, and there was no significant change in the baseline FEV1 of any subject prior to either challenge throughout the study period. When compared to placebo, the bronchial responsiveness to exercise and methacholine was significantly attenuated in the children who had received inhaled BDP for at least 1 month. There was no relationship between the bronchial responsiveness to methacholine and exercise. There was no significant difference in the bronchial responsiveness to either stimulus in the atopic and nonatopic children. The results of this study suggest that immunoglobulin E (IgE)- and non-IgE-mediated airway inflammation are important in exercise- and methacholine-induced bronchoconstriction in children with recurrent wheeze, although it is probable that different mechanisms are responsible.

Topics: Administration, Inhalation; Administration, Topical; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Asthma, Exercise-Induced; Beclomethasone; Bronchial Provocation Tests; Bronchoconstrictor Agents; Child; Double-Blind Method; Exercise; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Methacholine Chloride; Prospective Studies; Recurrence; Respiratory Mechanics; Respiratory Sounds

Daily use of inhaled corticosteroids (ICS) reduces exercise induced bronchoconstriction (EIB) in asthmatic children. A high single dose of ICS also provided acute protection against EIB. Objective of this study is to investigate whether a low single dose of ICS offers protection against EIB in asthmatic children.. 31 Mild asthmatic children not currently treated with inhaled corticosteroids, 5-16 years, with EIB (fall in FEV0.5/1 ≥ 13%) were included in a prospective intervention study. They performed two ECT's within 2 weeks. Four hours before the second test children inhaled 200 μg beclomethasone-dipropionate (BDP) with a breath-actuated inhaler (BAI).. The median fall in FEV0.5/1 after 200 μg BDP was significantly reduced from 30.9% at baseline to 16.0% (P < 0.001). Twenty children (64.5%) showed a good response to 200 μg BDP (≥ 50% decrease in fall of FEV0.5/1), while 8 children showed a moderate response (25-50%), and three children showed no response at all (< 25%).. A low single dose ICS offers acute protection against EIB in the majority of asthmatic children not currently treated with inhaled corticosteroids.

Topics: Adolescent; Asthma, Exercise-Induced; Beclomethasone; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Nebulizers and Vaporizers; Prospective Studies

Inhaled corticosteroids are widely used for the treatment of bronchial asthma, and a long-term treatment with inhaled corticosteroids is effective in preventing exercise-induced bronchoconstriction (EIB). We have previously shown that hyperosmolarity, and cooling and rewarming induced interleukin-8 (IL-8) expression in human bronchial epithelial cells (BEC). However, the effect of inhalant corticosteroids on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production has not been determined. To clarify these issues, we examined the effect of inhalant corticosteroids, beclomethasone dipropionate (BDP), and budesonide (BUD) on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. The results showed that BDP and BUD inhibited hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. Because our previous studies have shown that p38 mitogen-activated protein (MAP) kinase and c-Jun-NH(2)-terminal kinase (JNK) regulate hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production, we examined the effect of BDP and BUD on p38 MAP kinase and JNK activation. The results showed that BDP and BUD did not inhibit hyperosmolarity-induced and cooling-induced p38 MAP kinase and JNK activation. These results indicated that inhalant corticosteroids inhibited hyperosmolarity-, and cooling and rewarming-induced IL-8 and RANTES production; however, the mechanism of inhaled corticosteroid-mediated inhibition of hyperosmolarity-induced, and cooling and rewarming- induced cytokine production remains to be clarified.

Topics: Administration, Inhalation; Administration, Topical; Anti-Inflammatory Agents; Asthma, Exercise-Induced; Beclomethasone; Body Temperature Regulation; Bronchi; Budesonide; Cells, Cultured; Chemokine CCL5; Epithelial Cells; Glucocorticoids; Humans; Interleukin-8; Water-Electrolyte Balance

The effect of medication on peripheral airway obstruction was examined in cases of bronchial asthma. Subjects were 1) patients with exercise-induced asthma, 2) an animal model of hyperventilation-induced asthma and 3) patients with chronic asthma. Peripheral airway obstruction was induced in 30 of 51 patients with exercise-induced asthma. Induction of peripheral airway obstruction was protected significantly by procaterol. Cromoglycate was effective in 12 of 17 patients but ipratropium was not effective against induction of peripheral airway obstruction. In the animal model, humid air inhalation, procaterol and ipratropium completely prevented hyperventilation-induced bronchoconstriction, but cromoglycate caused only partial prevention. In cases of chronic asthma with peripheral airway obstruction, beclomethasone inhalation reduced the symptom rating rapidly, but no changes were observed in pulmonary function and threshold of airway responsiveness. Cromoglycate was started in patients with chronic asthma who had been treated with beclomethasone. After cromoglycate administration, therapeutic rating decreased, but increased again after 8 weeks of cromoglycate therapy. Peripheral airway obstruction induced by exercise or hyperventilation could be prevented by adequate premedication, but chronic peripheral airway obstruction was difficult to treat.

Topics: Administration, Inhalation; Airway Obstruction; Animals; Asthma; Asthma, Exercise-Induced; Beclomethasone; Cromolyn Sodium; Histamine; Humans; Ipratropium; Procaterol; Rabbits

Topics: Adolescent; Adult; Albuterol; Anaphylaxis; Asthma; Asthma, Exercise-Induced; Beclomethasone; Exercise; Humans; Hydroxyzine; Ketotifen; Urticaria

To assess the sport activities and the previous management of asthmatic children with an exercise-induced bronchial obstruction (EIB), we studied 124 children, aged 8-17 years, with a history of EIB, which was confirmed in a free-running exercise test. Participation in school sports was regular in 38% of the children, irregular in 45% and absent in 17%. Participation in sports outside the school was even lower: In 26% regularly, 18% irregularly and absent in 56%. 17% of all children were not active in any sport. EIB had previously been diagnosed in 38 (31%) children, and 20 (16%) of these had received an appropriate prophylactic medication. Children who received prophylaxis participated significantly more often in school sports (p less than 0.01) and in other sports (p less than 0.05), compared with those who had been diagnosed but had not received prophylaxis. After exercise, peak expiratory flow decreased by a mean of 41% of the preexercise values, but following a prophylactic administration of 0.2 mg Salbutamol-aerosol it decreased only by 2%. A complete protection of EIB was achieved in 94% of the children and the mean %-protection was 95%. The protective effect of 2 mg DNCG-aerosol in 21 children was significantly lower (53%, p less than 0.05) than that of salbutamol and a complete protection was achieved in only 71% (p less than 0.025) of the children.

Topics: Airway Resistance; Albuterol; Asthma; Asthma, Exercise-Induced; Beclomethasone; Child; Cromolyn Sodium; Drug Therapy, Combination; Exercise Test; Female; Humans; Male; Sports; Theophylline