Protection Against Exercise-Induced Bronchoconstriction Two Hours After a Single Oral Dose of Montelukast

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 (FEV₁) ≥ 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 FEV₁ (from pre-exercise FEV₁) 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 ≤ 0.001); numerically greater improvements were seen at 12 hours and 24 hours. A quicker time to recovery after challenge (p ≤ 0.001) and a smaller area under the curve for percent-fall in FEV₁ during 60 minutes after challenge (p ≤ 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.     

An evaluation of levalbuterol HFA in the prevention of exercise-induced bronchospasm.

BACKGROUND: Exercise-induced bronchospasm (EIB) affects up to 90% of all patients with asthma. Objective. This study evaluated the ability of levalbuterol hydrofluoroalkane (HFA) 90 mug (two actuations of 45 microg) administered via metered dose inhaler (MDI) to protect against EIB in mild-to-moderate asthmatics. METHODS: This was a randomized, double-blind, placebo-controlled, two-way cross-over study. Patients with asthma (n = 15) were > or =18 years, had a > or =6-month history of EIB, > or = 70% baseline predicted forced expiratory volume in 1 second (FEV1), and a 20% to 50% decrease in FEV(1) after treadmill exercise challenge using single-blind placebo MDI. Levalbuterol or placebo was self-administered 30 minutes before exercise. Treatment sequences were separated by a 3-to 7-day washout period. Spirometry was performed predose, 20 minutes postdose/pre-exercise, and 5, 10, 15, 30, and 60 minutes post-exercise. The primary endpoint was the maximum percent decrease in FEV1 from baseline (postdose/pre-exercise). The percentage of protected (< or = 20% decrease in post-exercise FEV1) patients was also assessed. RESULTS: Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV1 compared with placebo (LS mean +/- SE; -4.8% +/- 2.8% versus -22.5% +/- 2.8%, respectively). For levalbuterol, 14/15 (93.3%) patients had < 20% decrease in post-exercise FEV1 compared with 8/15 (53.3%) for placebo (p = 0.0143). Treatment was well tolerated. CONCLUSION: Levalbuterol HFA MDI (90 microg) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated. CLINICAL IMPLICATIONS: Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB.     

Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction

BACKGROUND AND OBJECTIVE: It has been previously established that montelukast provides protection against exercise-induced bronchoconstriction (EIB) after a single dose. The present objective was to assess the onset and duration of this protective action in a trial that included both positive and negative controls. METHODS: A randomized, active-controlled and placebo-controlled, double-blind, double-dummy, three-way crossover study was conducted in 47 patients (age range, 15 to 44 years) in whom there was a 20 to 40% fall in FEV(1) following exercise (DeltaFEV(1)). In randomized sequence, patients received oral montelukast (10 mg), placebo, or inhaled salmeterol (50 microg) as a positive control. Dosing was followed by exercise challenges at 2, 8.5, and 24 h. The primary end point was maximum DeltaFEV(1) at 2 h postdose. Secondary end points included maximum DeltaFEV(1) at the two later time points, and other measures (including recovery time and need for beta-agonist rescue) at all time points. RESULTS: The maximum DeltaFEV(1) magnitudes at 2, 8.5, and 24 h were significantly smaller after montelukast administration than after placebo administration (least squares mean [+/- SE], 13.2 +/- 1.2%, 11.7 +/- 1.2%, and 10.0 +/- 1.1% vs 21.8 +/- 1.2%, 16.8 +/- 1.3%, and 14.0 +/- 1.1%, respectively; p 相似文献   

Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction

Accumulating evidence shows that cysteinyl leukotrienes are the most important mediators in exercise-induced bronchoconstriction (EIB). In contrast to several studies in adults, there are few long-term studies of leukotriene receptor antagonists (LTRAs) in children with EIB. The aim of this study was to assess the prolonged clinical and bronchoprotective effects of montelukast in asthmatic children with EIB. We randomly assigned 64 asthmatic children with EIB. Forty subjects received montelukast (5 mg/day), and 24 subjects received placebo once daily for 8 weeks. Exercise challenge was performed before and after 8 weeks of treatment. Of the 40 patients in the montelukast group, 28 patients crossed over after 8 weeks. The response was measured as asthma symptom score, maximum percent fall in forced expiratory volume in 1 sec (FEV(1)) from pre-exercise baseline, and time to recovery of FEV(1) to within 10% of pre-exercise baseline (time to recovery). Following 8 weeks of treatment with montelukast, the montelukast group compared with placebo showed significant improvements in all endpoints, including asthma symptom score, maximum percent fall in FEV(1) after exercise, and time to recovery. In the cross-over group, even 8 weeks after stopping montelukast treatment, all endpoints were significantly and persistently improved. These results indicate that montelukast provides clinical protection from airway hyperresponsiveness in asthmatic children with EIB, and suggest that LTRAs may be useful for the long-term management of asthmatic children with EIB.     

孟鲁司特钠治疗运动诱发性支气管收缩的临床研究

目的　观察孟鲁司特钠治疗轻、中度支气管哮喘(简称哮喘)并发运动诱发支气管收缩(EIB)或运动性哮喘(EIA)的治疗及预防作用。方法　采用前瞻性开放、自身治疗前、后对照的方法。选择轻、中度哮喘并运动激发试验阳性患者30例,给予孟鲁司特钠每晚10mg治疗1个月。分别于治疗前1d、治疗后3d及4周进行运动激发试验。主要观察运动后的前60min一秒钟用力呼气容积(FEV1)自基线下降的百分比时间曲线下面积(AUC0~60min),运动后FEV1最大下降程度(FEV1最低值)及自最低FEV1恢复至运动前基值5%以内所需的时间(FEV1最低值恢复时间)。结果　孟鲁司特钠治疗前1d、治疗后3d和治疗后4周,运动激发试验后AUC0~60min分别为(39±21)、(13±14)、(12±14)%·min,治疗前、后比较差异有统计学意义(P<001);FEV1最低值分别为(18±06)、(21±06)、(23±08)L,治疗前、后比较差异有统计学意义(P<001);FEV1最低值恢复时间分别为(51±36)、(26±28)、(25±33)min,治疗前、后比较恢复时间显著缩短(P<001),并持续1个月。EIB/EIA患者孟鲁司特钠治疗前、后肺功能[FEV1、峰流速(PEFR)]均可维持接近正常且无明显变化。吸入糖皮质激素不能预防EIB/EIA。结论　孟鲁司特钠对轻度哮喘患者并发EIB/EIA疗效和预防作用显著,而且安全、快捷。     

Acute relief of exercise-induced bronchoconstriction by inhaled formoterol in children with persistent asthma

STUDY OBJECTIVE: To compare the acute bronchodilatory effect of the long-acting beta2-agonist formoterol against the short-acting beta2-agonist (SABA) terbutaline during exercise-induced bronchoconstriction (EIB) in children with asthma. DESIGN: A randomized, double-blind, placebo-controlled, crossover study of the immediate effect of formoterol, 9 microg, vs terbutaline, 0.5 mg, and placebo administered as dry powder at different study days. Exercise challenge test was used as a model of acute bronchoconstriction. PATIENTS: Twenty-four 7- to 15-year-old children with persistent asthma. INTERVENTIONS: The children performed standardized treadmill exercise tests, breathing dry air, with a submaximal workload. Study medication was administered 5 min after exercise if FEV1 dropped > or = 15% within 5 min after exercise. FEV1 and forced expiratory flows were measured repeatedly until 60 min after dose. RESULTS: Formoterol and terbutaline offered a significant acute bronchodilatory effect from 3 min after dose compared with placebo (p < 0.001). There was no difference between formoterol and terbutaline in FEV1 5 min after dose (p = 0.15), with a mean increase from each predrug baseline of 62% of the maximum increase for both. Median times to recovery within 5% of baseline FEV1 were 5.0 min and 7.4 min for formoterol and terbutaline, respectively (p = 0.33). CONCLUSION: Single-dose formoterol, 9 microg, via dry powder inhaler provided an acute bronchodilatory effect similar to terbutaline during EIB in schoolchildren with persistent asthma. Formoterol is at least as effective as SABA and may be considered an alternative in the treatment of acute bronchoconstriction in school children.     

Evidence of the rapid protective effect of formoterol dry-powder inhalation against exercise-induced bronchospasm in athletes with asthma

BACKGROUND: Although formoterol, a new long-acting beta(2)-adrenergic agonist, has a rapid bronchodilating action, no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm (EIB). Aim: The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes. METHODS: The protective effect of a formoterol (12 microg) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes (13 males, mean age 16.8 years), in a double-blind, placebo-controlled, two-period cross-over study. On each treatment day, the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo. RESULTS: Formoterol induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration (p = 0.007 and p = 0.004); placebo treatment had no effect on EIB, the maximum percent fall in FEV(1) after exercise being 29.3 +/- 14.3% and 22.9 +/- 13. 7% at 15 min and 4 h, respectively. Formoterol offered good protection against EIB in 12 athletes (86%) who experienced a decrease in FEV(1) after exercise <10% both 15 min and 4 h after administration. The mean maximum percent fall in FEV(1) after formoterol was 5.9+/-7.2% at 15 min (p < 0.0001), and 5.8 +/- 6.9% at 4 h (p < 0.0001). There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol, nor was the heart rate at the end of exercise significantly different on the 2 treatment days. No side effect was observed in either group. CONCLUSIONS: This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration.     

Inhaled hyaluronic acid against exercise-induced bronchoconstriction in asthma

Hyaluronic acid (HA) is a polysaccharide that is present in human tissues and body fluids. HA has various functions, including a barrier effect, water homeostasis, stabilizing the extracellular matrix, increased mucociliary clearance and elastin injury prevention. It may therefore exert prophylactic activity in the treatment of asthma. We tested the hypothesis that HA inhalation will prevent exercise-induced bronchoconstriction (EIB) in a randomised double-blinded placebo-controlled crossover study. Sixteen asthmatic patients with EIB were included in the study (mean (SD)) (age 24.5 (7.3) yr, FEV1 88.6 (11.3) %predicted, PC20 methacholine (g-mean (SD in DD)) 0.4 (1.5) mg/ml). On two separate visits an exercise challenge was performed 15 min post-inhalation of either HA (3 ml 0.1% in PBS) or placebo (3 ml PBS). The maximum fall in FEV1 and the AUC 30 min post-exercise were used as outcomes. After inhalation of both HA and placebo, baseline FEV1 decreased significantly (HA 4.1 (3.1)%, placebo 2.9 (4.1)%, P<0.017). The maximum fall in FEV1 following exercise challenge was not significantly different between HA versus placebo (median HA 22.50%, placebo 27.20%, P=0.379), as was the AUC (median HA 379.3 min*%fall, placebo 498.9 min*%fall, P=0.501). We conclude that at the current dose, inhaled HA does not significantly protect against EIB. This suggests that HA is not effective as a prophylaxis for EIB in patients with asthma.     

Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: a pilot study

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.     

Safety of sputum induction with hypertonic saline solution in exercise-induced bronchoconstriction

BACKGROUND: The safety of sputum induction (SI) is well described in stable asthma, but the safety of SI in exercise-induced bronchoconstriction (EIB) has not been established. OBJECTIVES: Our goals were to examine the relationship between the severity of EIB and bronchoconstriction during SI, and to determine if SI conducted after exercise challenge increases the risk of excess bronchoconstriction during SI. METHODS: SI was conducted in 32 patients with mild-to-moderate asthma (baseline FEV(1), 86 +/- 9% of predicted [mean +/- SD]) with EIB (15 to 63% reduction in FEV(1) following exercise challenge) following pretreatment with albuterol using 3% saline solution and repeated on a separate day 30-min after exercise challenge. RESULTS: There was a reduction in peak expiratory flow rate (PEFR) during SI without exercise (mean maximum reduction vs baseline, 4.0% at 10 min; 95% confidence interval [CI], 1.0 to 7.1; p = 0.02) and during SI 30 min following exercise (mean maximum reduction vs baseline, 5.2% at 8 min; 95% CI, 1.0 to 7.5; p < or = 0.01); however, there was no difference between the PEFR reductions during SI without or following exercise challenge. The best predictor of reduction in PEFR during SI was the preprocedure FEV(1), while the severity of EIB was not associated with bronchoconstriction during SI. CONCLUSIONS: We conclude that SI can be performed safely following exercise challenge in asthmatics with EIB, and that the severity of EIB prior to SI is not a major determinant of bronchoconstriction during SI.     

An Evaluation of Levalbuterol HFA in the Prevention of Exercise-Induced Bronchospasm

Background. Exercise-induced bronchospasm (EIB) affects up to 90% of all patients with asthma. Objective. This study evaluated the ability of levalbuterol hydrofluoroalkane (HFA) 90 μg (two actuations of 45 μg) administered via metered dose inhaler (MDI) to protect against EIB in mild-to-moderate asthmatics. Methods. This was a randomized, double-blind, placebo-controlled, two-way cross-over study. Patients with asthma (n = 15) were ≥18 years, had a ≥6-month history of EIB, ≥ 70% baseline predicted forced expiratory volume in 1 second (FEV₁), and a 20% to 50% decrease in FEV₁ after treadmill exercise challenge using single-blind placebo MDI. Levalbuterol or placebo was self-administered 30 minutes before exercise. Treatment sequences were separated by a 3-to 7-day washout period. Spirometry was performed predose, 20 minutes postdose/pre-exercise, and 5, 10, 15, 30, and 60 minutes post-exercise. The primary endpoint was the maximum percent decrease in FEV₁ from baseline (postdose/pre-exercise). The percentage of protected (≤ 20% decrease in post-exercise FEV₁) patients was also assessed. Results. Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV₁ compared with placebo (LS mean ± SE; ?4.8% ± 2.8% versus ?22.5% ± 2.8%, respectively). For levalbuterol, 14/15 (93.3%) patients had < 20% decrease in post-exercise FEV₁ compared with 8/15 (53.3%) for placebo (p = 0.0143). Treatment was well tolerated. Conclusion. Levalbuterol HFA MDI (90 μg) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated. Clinical Implications. Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB.     

Bronchodilatation and attenuation of exercise-induced bronchospasm by PY 108-068, a new calcium antagonist

The effect of a new dihydropyridine-derivative calcium antagonist, PY 108-068, on resting and postexercise flow rates was evaluated in 12 adult asthmatic subjects in a double-blind, randomized, placebo-controlled, cross-over study. The study consisted of 2 periods, each lasting for 3 days. For a given period a single dose of PY 108-068 (or placebo) was given orally, 75 mg on the first day and 150 mg on the second and third day. Spirometry was obtained at 30-min intervals thereafter. On Day 3, 75 min after the medication was given, a 6-min treadmill exercise test was performed breathing dry air. The mean maximal FEV1 recorded after 150 mg of PY 108-068 on Day 2 was 15 +/- 4% higher than the daily baseline (p less than 0.05), whereas after placebo the maximal FEV1 value was not different from the daily baseline. Also, the mean FEV1 values, expressed as percent of the daily predrug baseline, were significantly higher at 2 and 3 h after 150 mg of PY 108-068 than the respective values after placebo (110 +/- 4 compared with 95 +/- 1, and 106 +/- 5 compared with 91 +/- 3, respectively). Exercise-induced bronchospasm (EIB), expressed as maximal percent fall in FEV1 from preexercise baseline, was attenuated by PY 108-068 as compared with placebo (% delta FEV1 of 20 +/- 6 and 40 +/- 4, respectively; p less than 0.001). Protection against EIB did not correlate with the resting bronchodilation induced by PY 108-068, but was more likely if the patient had eosinophilia. Thus, PY 108-068 not only attenuates EIB but also causes resting bronchodilation, a unique finding for calcium channel blockers.     

Eosinophils play a major role in the severity of exercise-induced bronchoconstriction in children with asthma

Exercise-induced bronchoconstriction (EIB) was associated with eosinophilic airway inflammation, bronchial hyperresponsiveness (BHR), atopy and airway obstruction. To understand the pathogenesis of EIB, we determine whether eosinophil is more related to the mechanism of EIB than atopy, BHR and airway obstruction. This study comprised 268 asthmatic children who underwent lung function test, methacholine challenge test, exercise challenge test, and blood tests for total IgE levels and total eosinophil counts (TEC). Urine eosinophil protein X (EPX) levels after exercise were measured by using ELISA method. EIB was observed in 195 of 268 asthmatics (72.8%). Asthmatics with EIB showed significantly increased TEC (P < 0.01) and decreased log PC(20) as compared with asthmatics without EIB. Maximal percent fall in FEV(1) after exercise was significantly correlated with TEC, log IgE, FEF(25-75%), log PC(20) (P < 0.001, respectively) and FEV(1) (P = 0.013). When the same study was carried out in nonatopic asthmatics, those with EIB showed significantly increased TEC (P = 0.01) compared with those without EIB; however, log PC(20), FEV(1), and FEF(25-75%) showed no significant differences between the two groups of nonatopic asthmatics. In addition, there was a significant correlation between the severity of EIB and TEC in nonatopic asthmatics. Urine EPX/Cr levels after exercise were correlated with the severity of EIB (r = 0.238, P = 0.014). Blood eosinophils and urine EPX/Cr after exercise correlate significantly with the maximal percent fall in FEV(1) after exercise, therefore EIB may reflect a state of eosinophilic inflammation in the airway of asthmatic children.     

Proventil HFA Prevents Exercise-Induced Bronchoconstriction in Children

Short-acting inhaled beta₂-agonists used just prior to exercise are an effective method for preventing exercise-induced bronchoconstriction (EIB) in children. This was a randomized, single-blind, placebo-controlled, four-period crossover study that compared the effectiveness of albuterol formulated in hydrofluoro-alkane-134a (HFA) to albuterol formulated in chlorofluorocarbons (CFCs) and to placebo in protecting asthmatic children age 6-11 from EIB. Patients self-administered either HFA albuterol, two different CFC albuterol products, or placebo 30 min prior to exercise challenge. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 min after the exercise challenge was completed. The smallest percent change from the predose forced expiratory volume in 1 sec (FEV₁) after exercise challenge was similar for the three active treatments, and each of the active treatments was significantly better than placebo. Each active treatment had significantly fewer patients unprotected from EIB (unprotected defined as having ≥20% fall in FEV, after exercise challenge) than placebo. Changes in heart rate, blood pressure and electrocardiogram     

Montelukast administered in the morning or evening to prevent exercise-induced bronchoconstriction in children

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.     

Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma

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.     

Proventil HFA Prevents Exercise-Induced Bronchoconstriction in Children

Short-acting inhaled beta₂-agonists used just prior to exercise are an effective method for preventing exercise-induced bronchoconstriction (EIB) in children. This was a randomized, single-blind, placebo-controlled, four-period crossover study that compared the effectiveness of albuterol formulated in hydrofluoro-alkane-134a (HFA) to albuterol formulated in chlorofluorocarbons (CFCs) and to placebo in protecting asthmatic children age 6-11 from EIB. Patients self-administered either HFA albuterol, two different CFC albuterol products, or placebo 30 min prior to exercise challenge. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 min after the exercise challenge was completed. The smallest percent change from the predose forced expiratory volume in 1 sec (FEV₁) after exercise challenge was similar for the three active treatments, and each of the active treatments was significantly better than placebo. Each active treatment had significantly fewer patients unprotected from EIB (unprotected defined as having ≥20% fall in FEV, after exercise challenge) than placebo. Changes in heart rate, blood pressure and electrocardiogram     

Lack of tolerance to the protective effect of montelukast in exercise-induced bronchoconstriction in children.

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.     

Fish oil supplementation reduces severity of exercise-induced bronchoconstriction in elite athletes

In elite athletes, exercise-induced bronchoconstriction (EIB) may respond to dietary modification, thereby reducing the need for pharmacologic treatment. Ten elite athletes with EIB and 10 elite athletes without EIB (control subjects) participated in a randomized, double-blind crossover study. Subjects entered the study on their normal diet, and then received either fish oil capsules containing 3.2 g eicosapentaenoic acid and 2.2 g docohexaenoic acid (n-3 polyunsaturated fatty acid [PUFA] diet; n = 5) or placebo capsules containing olive oil (placebo diet; n = 5) taken daily for 3 weeks. Diet had no effect on preexercise pulmonary function in either group or on postexercise pulmonary function in control subjects. However, in subjects with EIB, the n-3 PUFA diet improved postexercise pulmonary function compared with the normal and placebo diets. FEV1 decreased by 3 +/- 2% on n-3 PUFA diet, 14.5 +/- 5% on placebo diet, and 17.3 +/- 6% on normal diet at 15 minutes postexercise. Leukotriene (LT)E4, 9alpha, 11beta-prostaglandin F2, LTB4, tumor necrosis factor-alpha, and interleukin-1beta, all significantly decreased on the n-3 PUFA diet compared with normal and placebo diets and after the exercise challenge. These data suggest that dietary fish oil supplementation has a markedly protective effect in suppressing EIB in elite athletes, and this may be attributed to their antiinflammatory properties.     

Field exercise vs laboratory eucapnic voluntary hyperventilation to identify airway hyperresponsiveness in elite cold weather athletes

STUDY OBJECTIVE: For the 2002 Winter Olympic Games, athletes were required to submit objective evidence of asthma or exercise-induced bronchoconstriction (EIB) for approval to inhale a beta(2)-agonist. Eucapnic voluntary hyperventilation (EVH) was recommended as a laboratory challenge that would identify airway hyperresponsiveness (AHR) consistent with EIB. The objective was to compare the change in FEV(1) provoked by EVH with that provoked by exercise in cold weather athletes. DESIGN: Spirometry was measured before and for 15 min after challenges. The two challenges were performed in random order at least 24 h apart. SETTING: EVH was performed in the laboratory at 19 degrees C, and exercise took place in the field in the cold (2 degrees C, 45% relative humidity). PARTICIPANTS: Thirty-eight athletes (25 female subjects; median age, 16 years). INTERVENTIONS: For the EVH, athletes inhaled dry air containing 5% carbon dioxide for 6 min at a target ventilation equivalent to 30 times baseline FEV(1). Exercise was performed by cross-country skiing, ice skating, or running for 6 to 8 min. MEASUREMENTS AND RESULTS: AHR consistent with EIB was defined as >or= 10% fall in FEV(1) from baseline after challenge. Eleven athletes were exercise positive (EX+) [FEV(1) fall, 20.5 +/- 7.3%], and 17 athletes were EVH positive (FEV(1) fall, 14.5 +/- 4.5%) [mean +/- SD]. Of 19 subjects with AHR, 58% were identified by exercise and 89% were identified by EVH. EVH identified 9 of 11 subjects who were EX+ and a further 8 subjects with potential for EIB. The average ventilation during EVH was 28 times FEV(1). CONCLUSION: Performing EVH for 6 min in the laboratory had a greater chance of identifying AHR in these athletes compared with 6 to 8 min of field exercise in the cold. The EVH test will be useful to evaluate elite summer sports athletes whose widely different forms of exercise provide an "equipment" challenge to any laboratory.