Prevention Of Exercise-induced Asthma Research Articles

Cromoglycate, reproterol, or both—what’s best for exercise-induced asthma?

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

Prevention of Exercise-induced Asthma by a Fixed Combination of Disodium Cromoglycate plus Reproterol Compared with Montelukast in Young Patients

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.

Urinary and Blood Concentrations of β2-Agonists in Trained Subjects: Comparison between Routes of Use

We aimed to assess the plasma and urine concentrations of beta2-agonists and evaluate the difference between three routes of administration in trained adults in order to distinguish doping from prevention of exercise-induced asthma. Ten young healthy Caucasian male subjects received during a four treatment period study: 1) inhaled salbutamol (S(I)) 2 x 100 microg t.i.d. for 3 days, 2) inhaled formoterol (F(I)) 2 x 12 microg b.i.d. for 3 days, 3) a single subcutaneous injection of salbutamol (S(S)) 0.5 mg, and 4) salbutamol 2 x 2 mg t.i.d. orally for 3 days (S(O)). Blood samples were taken during the first and the third day of experimentation at baseline, 30 min, 1 h, 2 h, 4 h and 6 h after administration; additional blood samples were drawn at 15 min for S(I), S(S) and F(I) and at 12 h for F(I). Urinary samples were collected at baseline, 2 h, 4 h, 6 h and 12 h after administration. Urinary concentrations were 20 to almost 50 times higher after S(O) than after S(I). Mean urinary concentration after S(O) increased to above 800 ng.mL(-1) within the two hours and above 1000 ng.mL(-1) at 6 to 12 hours post-drug administration. Urinary concentrations after S(S) were maximal during the first 2 hours (mean: 340 +/- 172 ng.mL(-1)). Plasma concentrations were very low, whatever the routes of administration. Results showed that we could eliminate the use of S(I) (authorized) and S(S) administration when individual urinary concentrations are higher than 230 ng.mL(-1) and 615 ng.mL(-1), respectively. Therefore, at rest, the cut-off value used to discriminate therapeutic from doping salbutamol intake could be fixed at 250 ng.mL(-1) instead of the 1000 ng.mL(-1) still authorized by international committees.

Single-Dose Agents in the Prevention of Exercise-Induced Asthma

Exercise-induced asthma (EIA) refers to the transient narrowing of the airways that occurs after vigorous exercise in 50-60% of patients with asthma. The need to condition the air inspired during exercise causes water to be lost from the airway surface, and this is thought to cause the release of inflammatory mediators (histamine, leukotrienes, and prostaglandins) from mast cells. EIA is associated with airway inflammation and its severity is markedly reduced following treatment with inhaled corticosteroids. Drugs that inhibit the release of mediators and drugs that inhibit their contractile effects are the most successful in inhibiting EIA. Single doses of short-acting beta(2)-adrenoceptor agonists, given as aerosols immediately before exercise, are very effective in the majority of patients with asthma, providing about 80% protection for up to 2 hours. Long-acting beta(2)-adrenoceptor agonists (LABAs) given in single doses can be effective for up to 12 hours when used intermittently, but tolerance to the protective effect occurs if they are taken daily. Drugs such as cromolyn sodium (sodium cromoglicate) and nedocromil given as aerosols are less effective than beta(2)-adrenoceptor agonists (beta(2)-agonists), providing 50-60% protection for only 1-2 hours, but they have some advantages. They do not induce tolerance, the aerosol dosage can be easily titrated for the individual, and the protective effect is immediate. Because they cause no significant adverse effects, multiple doses can be used in a day. Leukotriene receptor antagonists, such as montelukast and zafirlukast, are also used for the prevention of EIA and provide 50-60% protection for up to 24 hours when given as tablets. Tolerance to the protective effect does not develop with regular use. If breakthrough EIA occurs, a beta(2)-agonist can be used effectively for rescue medication. For those patients with more persistent symptoms, the use of a LABA in combination with an inhaled corticosteroid has raised a number of issues with respect to the choice of prophylactic treatment for EIA. The most important issue is the development of tolerance to the protective effect of a LABA such that extra treatment may be needed in the middle of a treatment period. Recommending extra doses of a beta(2)-agonist to control EIA is not advisable on the basis that multiple doses can enhance the severity of EIA, delay spontaneous recovery from bronchoconstriction, and enhance responses to other contractile stimuli. It is time to take into account the advantages and disadvantages of the different drugs available to prevent EIA and to recognize that there are some myths related to their use in EIA.

Salmeterol. A review of its pharmacological properties and clinical efficacy in the management of children with asthma.

Salmeterol xinafoate is a selective beta 2-adrenoceptor agonist indicated for the maintenance treatment of adults and children with asthma. When administered as a dry powder or aerosol, salmeterol produces bronchodilation for at least 12 hours and protects against methacholine and exercise-induced bronchoconstriction. Salmeterol is not recommended for the treatment of acute exacerbations of asthma. Recent clinical studies have demonstrated the efficacy and tolerability of inhaled salmeterol in the management of asthma in children. Salmeterol improved symptom control and lung function more effectively than placebo or regularly administered salbutamol. In children who were symptomatic despite regular inhaled corticosteroid therapy, the addition of salmeterol to treatment produced a significant improvement in morning and evening peak expiratory flow and forced expiratory volume in 1 second, and a significant reduction in the incidence of asthma exacerbations compared with placebo. Notably, the long duration of action of salmeterol makes it particularly suitable for the prevention of nocturnal asthma symptoms and exercise-induced asthma (EIA) in children. Current data suggest that salmeterol should not be used as a substitute for corticosteroid therapy in children, but rather as an adjunct to therapy. Thus, salmeterol may be a suitable adjunct to therapy in children with asthma receiving inhaled corticosteroids. In addition, salmeterol also has a potentially important role in the prevention of EIA and nocturnal asthma symptoms.

Clinical management of asthma in the 1990s. Current therapy and new directions.

Asthma is a serious global health problem affecting nearly 100 million people worldwide. Its rising prevalence and associated morbidity and mortality are of increasing concern. Traditionally, symptomatic control of bronchoconstriction with beta 2 agonists and theophylline has been the mainstay of therapy. However, during recent years, inflammation has been recognised as the predominant cause of reversible airway obstruction and airway hyperreactivity. As a result, the emphasis in treatment has shifted to the early use of inhaled corticosteroids to control airway inflammation. beta 2 agonists are best used on an as-needed basis for the relief of acute bronchoconstriction and for the prevention of exercise-induced asthma. Sustained release theophylline or an inhaled long-acting beta 2 agonist may effectively control nocturnal symptoms. Preliminary studies involving agents active in the 5-lipoxygenase pathway as preventive therapy are encouraging. Further studies are needed to define their role in the management of asthma.

The preventive effect and duration of action of two doses of inhaled furosemide on exercise-induced asthma in children

Background: Exercise-induced asthma can be prevented by treatment with inhaled furosemide. Objective: In this study we evaluated the effect and duration of action of two doses (15 and 30 mg) of inhaled furosemide in prevention of exercise-induced asthma in children. Methods: Ten children with exercise-induced asthma (8 boys and 2 girls, aged 6 to 13 years) were included in the study. Each patient was tested with three treatment regimens (placebo, 15 mg of furosemide, and 30 mg of furosemide) in random order on 3 separate days. Patients performed exercise challenges on a treadmill at 20 minutes and 1, 2, 3, and 6 hours after each treatment. Pulmonary function, urinary output, and fluid intake were monitored. Results: Both doses of furosemide had a significantly greater protective effect than placebo, but there was no significant difference between the two doses of furosemide. The higher dose of furosemide was associated with increased urinary output and had a longer duration of action. Conclusion: A 30 mg dose of furosemide is more effective for treatment of exercise-induced asthma in terms of duration but has a significant diuretic effect. (J A LLERGY C LIN I MMUNOL 1995;96:906-9.)

Inhibition of exercise‐induced‐asthma (EIA) by nedocromil sodium and sodium cromoglycate in children

Nedocromil sodium (Ned) 4 mg, sodium cromoglycate (SCG) 10 mg, and placebo were compared for their efficacy in preventing exercise-induced asthma. Nineteen asthmatic children aged six to 15 years performed a treadmill exercise test before and 20' after a single dose of drug in a double-blind trial. Both active drugs performed significantly better than placebo; in fact the exercise challenge resulted in a mean maximum fall in FEV1 of 26.1 +/- 14.9% after placebo, but only of 14.6 +/- 11.5% after SCG (P < 0.05), and 11.0 +/- 12.4% after Ned (p < 0.01). Measurements of PEFR gave similar results, while the effect of treatment on FEF 25-75 was significant for Ned alone (p < 0.05). Direct comparison between Ned and SCG at different time points demonstrated significant differences in FEV1 at 1 min (p < 0.05) with a better overall performance of Ned. In individual patients, complete protection was provided in 9 patients with SCG, in 14 patients with Ned and in 2 with placebo. No side effects were observed. This study suggests that at the dosages used there are only slight differences between SCG and Ned activity in the prevention of exercise-induced asthma.

Sources of stress in children with asthma.

Children experience stressors related to self-concept and school, family, and peer relationships. This study of children with asthma determined their perceptions of the frequency and severity of stressors they experience other than their asthma. Children with asthma are similar to peers with regard to perceptions of stressors. Teachers, health professionals, and parents should consider children with asthma as normal children who have an additional source of stress--a chronic illness. Results suggest perceptions of most stressors relate more strongly to gender-role development than to asthma. Children with asthma rated feeling left out of the group and not being good enough at sports as serious stressors. School personnel could be instrumental in encouraging management and prevention of exercise-induced asthma and promote all children's full participation in physical activities. Further examination of the relationship between stress and asthma is needed.

Terfenadine and prevention of exercise-induced asthma

Summary The use of terfenadine in the prevention of exercise-induced asthma has already been reported in the literature. This drug was administered to 8 children at doses of 2 mg/kg and to 6 children at a total standardized dose of 120 mg. Three hours following a free run, the results were compared with those obtained with the use of a placebo. There was no significant variation in the fall of FEV1 after administration of placebo (↓ 38 %, ↓ 34 %) and administration of Terfenadine (↓ 32.2 %, ↓ 32 %). However, three children from both groups, were totally protected with the antihistamine preparation. The FEV1 dropped to 41 % after placebo as compared to 10.3 % after terfenadine. The authors emphasize that this evaluation should be extended to larger groups, before confirming the validity of terfenadine in the prevention of EIA.

The Use of Spacers in the Prevention of Exercise-Induced Asthma

Asthmatic children who suffer from exercise-induced bronchoconstriction were administered Terbutaline through a spacer prior to exercise. The spacer was found to improve drug delivery if the patient had difficulty using a metered-dose inhaler properly and protected the patient from exercise-induced asthma.

Rimiterol and the prevention of exercise-induced asthma

The potential for rimiterol to protect athletes from exercise-induced asthma (EIA) has not been fully established. Ten athletes with asthma (15 to 30 years of age) undertook 8 minutes of submaximal exercise (80% of anaerobic threshold) on the treadmill ergometer, once after inhaling rimiterol and once after inhaling a placebo. Treatment with all bronchodilator drugs was stopped for the 12 hours preceding each exercise test. Two puffs (400 μg) of rimiterol or placebo were administered in a double-blind crossover manner 2 minutes before each exercise test. Lung function measurements were made before exercise and immediately, 5, 10, 15, 20, 25, and 30 minutes after completion of exercise. The results of a two-way analysis of variance revealed significant ( p < 0.01) difference in the FEV 1 scores obtained after rimiterol inhalation and placebo inhalation, 5, 10, 15, 20, 25, and 30 minutes after cessation of exercise. After inhalation of rimiterol, there were no significant changes in FEV 1. After inhaling the placebo, significant reductions ( p < 0.01) in FEV 1 occurred after cessation of exercise (5, 10, 15, and 20 minutes). All subjects exhibited EIA after placebo, and none after rimiterol. The mean maximum drop after exercise in FEV 1 after inhalation of rimiterol (2.807 ± 5.55) and placebo (24.54 ± 8.4) was significantly different (t = 6.849). It was concluded that inhalation of rimiterol 2 minutes before exercise afforded significant protection from EIA in all subjects tested.

Efficacy and duration of action of placebo responses in the prevention of exercise-induced asthma in children.

Exercise-induced bronchoconstriction, a common phenomenon in asthmatic children, may be prevented by the administration of appropriate drugs. In this study we evaluated the effect and duration of action of placebo (Freon gasses) administered to the patients as a protective drug. The maximum decrease in forced expiratory volume in 1 second (FEV1) after exercise testing was 40.3% +/- 3.10 at the initial screening session and, on different study days, 23.3% +/- 3.57, 28.8% +/- 3.86, and 33.7% +/- 3.71 30, 120, and 240 minutes, respectively, after the administration of Freon gasses. There was a linear trend indicating a reduction in protection with time. The placebo effect was marked 30-120 minutes after treatment (p less than 0.01) and completely disappeared after 4 hours. The placebo effect should always be considered in the evaluation of any new antiasthmatic drug.

Exercise-Induced Asthma (EIA): Its Prevention with the Combined Use of Ipratropium Bromide and Fenoterol

Until now very few studies have been performed on the prevention of exercise-induced asthma (EIA) in children with ipratropium bromide + fenoterol. This is why we decided to study 30 children aged between 6 and 15 years, whose EIA was confirmed by a test including a 6-min free race on day 1 of the study. The criterion was a decrease of more than 20% of the basal values of forced expiratory volume in 1 s (FEV1) or FMF. Children whose FEV1 or FMF baseline values were under 60% of those expected according to Polgard tables were excluded. Three tests were performed, the first to determine EIA, the second was performed 72 h later after inhalation of placebo. 72 h after day 2 the patients returned in order to repeat the test, but this time, aerosol therapy with the combination ipratropium + fenoterol was applied prior to the race. The dosage of the combination was 1 puff of aerosol per 10 kg body weight, up to a maximum of 4 puffs. Each puff of the combination contains 0.02 mg of ipratropium bromide and 0.05 mg fenoterol. Functional assessment of children was carried out by means of forced spirometry. There were no significant differences between the placebo group and the group which received no medication, but there was a significant difference between the treated group and the other two, not only in the FEV1 and FMF values but also in forced vital capacity TEST.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of exercise-induced asthma by theophylline

Although an association between exercise and provocation of asthma has been recognized for 300 yr, Jones et al., ’ pediatricians at Alder Hey Children’s Hospital in Liverpool, appear to have been the first to attempt to assess the effect of drugs as modulators of the exercise-induced bronchoconstriction phenomenon. Among the drugs they investigated was the choline salt of theophylline, a formulation that contains 64% anhydrous theophylline. In a single-dose study in which the subjects were administered anhydrous theophylline of the equivalent of between 4.5 and 5.8 mg/kg body weight several hours before exercise challenge, the postexercise fall in FEV, was completely or partially prevented in eight of nine subjects, and Jones et al. concluded that theophylline was protective against exercise-induced wheezing. In retrospect, it appears that the FEV, was measured before drug administration and not immediately before exercise and thus one does not know how much of the putative inhibition of exercise-induced asthma (EIA) was due to the bronchodilator effect of theophylline. Anderson et al.’ have emphasized the importance of measuring expiratory flow rate immediately before exercise so that the bronchodilating effect of the drug and its inhibitory effect on EIA can be considered separately. Nonetheless, in the study of Jones et al., the maximal FEV, after exercise was observed at a mean of 90 min after drug administration, which would coincide with the time of the peak serum theophylline concentration after administration of a rapidly absorbed product such as the one used. This was the first suggestion of a pharmacodynamic effect of theophylline in asthma. During the past decade there have been 10 additional studies2-” in which the efficacy of theophylline in the prevention of EIA has been investigated (Table I). While these studies are not strictly comparable because of a number of differences in experimental design and particularly in dose of theophylline, there are some generalizations that can be made. First, the results of these studies have uniformly shown that the-

Comparison of Aerosolized Atropine, Isoproterenol Atropine plus Isoproterenol, Disodium Cromoglycate and Placebo in the Prevention of Exercise-Induced Asthma

Exercise-induced asthma (EIA) has been reported to occur in up to 90% of asthmatic children and in up to 41% of children with only hay fever symptoms. The degree to which pharmacologic agents inhibit post-exercise asthma is not only important therapeutically, but also may provide clues as to the mechanisms of exercise-induced asthma. In the present study, we compared the effects on bronchial physiologic responses to a standard exercise load of no drug pre-treatment and pre-treatment with placebo, a specific blocker of mediator release, a β-adrenergic agonist, and an anticholinergic agent.

Comparison of aerosolized atropine, isoproterenol, atropine plus isoproterenol, disodium cromoglycate and placebo in the prevention of exercise-induced asthma

Comparison of aerosolized atropine, isoproterenol, atropine plus isoproterenol, disodium cromoglycate and placebo in the prevention of exercise-induced asthma

Use of exercise challenge to investigate possible tolerance to beta-adrenoceptor stimulation in asthma

The effect of prolonged salbutamol administration on beta-adrenoceptor function in asthma has been examined. Six adult patients received salbutamol tablets (16 mg daily) for between 4 and 20 weeks and six adolescents received salbutamol aerosol (800 μg daily) for 2–5 weeks. Before and after the treatment period the acute bronchodilator response to inhaled salbutamol and the ability of inhaled salbutamol to protect against exercise-induced asthma were examined. Lymphocyte beta-adrenoceptor function was also measured in the patients on tablet therapy. Inhaled salbutamol was less effective in protecting against exercise-induced asthma at the end of the treatment period in the patients who had received tablet therapy, but otherwise there was no significant change in beta-receptor function of either airways or lymphocytes. This apparent loss of efficacy of inhaled salbutamol in the prevention of exercise-induced asthma in some subjects, even when its acute bronchodilator effect is preserved, might reflect differences in the susceptibility of different beta-adrenoceptors to desensitization after prolonged stimulation: its clinical importance remains uncertain.

Prevention of Exercise-induced Asthma by Indoramin

Prevention of Exercise-induced Asthma by Indoramin

Letter: Prevention of exercise-induced asthma by indoramin.

Letter: Prevention of exercise-induced asthma by indoramin.