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。     

Effects of montelukast treatment and withdrawal on fractional exhaled nitric oxide and lung function in children with asthma

BACKGROUND: Leukotriene receptor antagonists (LTRAs) reduce fractional exhaled nitric oxide (Feno) concentrations in children with asthma, but the effect of LTRA withdrawal on Feno and lung function is unknown. We aimed to study the effect of treatment and withdrawal of montelukast, a LTRA, on airway inflammation as reflected by Feno and lung function in children with asthma. METHODS: A double-blind, randomized, placebo controlled, parallel group study was undertaken in 14 atopic children with mild persistent asthma who were treated with oral montelukast (5 mg/d for 4 weeks) and 12 atopic children with mild persistent asthma who received matching placebo. A follow-up visit was performed 2 weeks after montelukast or placebo withdrawal. RESULTS: Montelukast reduced Feno concentrations by 17% (p = 0.067), an effect that was more pronounced (35%) [p = 0.0029] when children with seasonal atopy who were exposed to relevant allergens during the treatment phase were excluded from analysis (n = 3). Compared to those at the end of treatment, Feno concentrations were increased 2 weeks after montelukast withdrawal (p = 0.023) concomitant with a reduction in absolute FEV(1) values (p = 0.011), FEV(1) percentage of predicted values (p = 0.006), FEV(1)/FVC ratio (p = 0.002), and forced expiratory flow at 25% to 75% of FVC values (p = 0.021). These changes were not observed in the placebo group. CONCLUSIONS: LTRAs reduce Feno concentrations in children with asthma, and withdrawal can result in increased Feno values and worsening of lung function in children 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.     

Onset and duration of attenuation of exercise-induced bronchoconstriction in children by single-dose of montelukast

Single-dose montelukast attenuates exercise-induced bronchoconstriction (EIB) in adults within 2 hours postdose and lasting through 24 hours. This study evaluated the onset and duration of EIB attenuation in children after a single dose of montelukast. A randomized, double-blind, placebo-controlled, two-period crossover study was performed. Patients (n = 66) aged 4-14 years, with preexercise forced expiratory volume in 1 second of (FEV(1)) ≥70% predicted and maximum percentage fall in FEV(1) of ≥20% at two screening exercise challenges were eligible. Patients were to receive single-dose montelukast (4 or 5 mg) or placebo before performing standardized exercise challenges at 2 and 24 hours postdose. A 3- to-7-day washout separated the two crossover periods. The primary end point was maximum percentage fall in FEV(1) after exercise challenge 2 hours postdose. Secondary end points included maximum percentage fall in FEV(1) after the 24-hour postdose challenge; each of the following at 2 and 24 hours postdose-maximum percentage fall in FEV(1) categorized as <10%, 10-20%, or >20%; area under the curve (AUC) during 60 minutes postchallenge; time to recovery of FEV(1) to within 5% of preexercise baseline; and need for rescue medication. The mean maximum percentage fall in FEV(1) after the 2-hour postdose exercise challenge was significantly attenuated after single-dose montelukast compared with placebo (15.35% versus 20.00%; p = 0.020). Montelukast was also significantly more effective than placebo for maximum percentage fall after the 24-hour challenge (12.92% versus 17.25%; p = 0.005), the categorized maximum percent fall in FEV(1) at 2 hours (p = 0.034), and AUC at 2 hours (p = 0.022) and 24 hours (p = 0.013). Single-dose montelukast provided rapid and sustained EIB attenuation in children. Clinicaltrials.gov identifier: NCT00534976.     

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.     

The effect of montelukast on bronchial hyperreactivity in preschool children

INTRODUCTION: The effect of montelukast therapy on bronchial hyperreactivity (BHR) as measured by the methacholine challenge test in preschool children has not yet been reported. OBJECTIVE: To determine the effect of montelukast (4 mg/d) on BHR as evaluated by a provocative concentration of a substance causing a 20% fall in FEV(1) (PC(20)) values in preschool asthmatic children. PATIENTS: A total of 26 preschool children (8 girls) aged 3.3 to 6.0 years (mean [+/- SD] age, 4.7 +/- 0.8 years) with mild asthma. DESIGN: Double-blind randomized, placebo controlled, crossover study. Each child received 4 weeks of treatment with 4 mg of either montelukast or placebo separated by a 2-week washout period. Primary outcomes were PC(20) values and the stage number (triple dose) at which FEV(1) values dropped by 20%(.) Post-montelukast therapy PC(20) was compared to those for the post-placebo period. RESULTS: Following 4 weeks of montelukast treatment, the mean PC(20) was 4.79 +/- 4.69 mg/mL, while after 4 weeks of placebo the mean PC(20) was 2.07 +/- 2.37 mg/mL (p = 0.001). The montelukast/placebo ratio for PC(20) was 2.56 with a 95% confidence interval (CI) of 1.71 to 3.99. The median difference in stage was one triple dose with a 95% CI of 0.5 to 1.5. CONCLUSIONS: Four weeks of treatment with montelukast resulted in a decreased BHR compared with placebo.     

A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

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.     

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.     

Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group

The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.     

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.     

3-min step test and treadmill exercise for evaluating exercise-induced asthma.

A simple exercise test would be useful for detecting exercise-induced asthma, a common problem in asthmatic children. The current study compared the 3-min step test with treadmill exercise for evaluating exercise-induced asthma in asthmatic children and assessed whether responses to both tests are influenced by baseline lung function and habitual physical activity. A series of 154 asthmatic children (84 male children; mean age 12.9 +/- 0.9 yrs) underwent a 3-min step-test and treadmill testing on different days within a week at least 24 h apart. Before both tests each subject did spirometry to obtain the baseline forced expiratory volume in one second (FEV1). After both exercise challenges all subjects did serial spirometry and the lowest FEV1 recorded over time was used to calculate the fall in FEV1 expressed as a percentage of the measured pre-exercise (baseline) value (% fall in FEV1) and the area above the FEV1 curve (AAC0-30 min) expressed as a percentage of the pre-exercise value. Changes in both exercise variables were also analysed in percentile subgroups defined by questionnaire answers on habitual physical activity in hours. The mean % fall in FEV1 was significantly higher for treadmill exercise than for the step test (15.0 +/- 7.5 versus 11.7 +/- 5.9); and the AAC0-30 min was larger for treadmill than for the step test (-261.6 +/- 139.9% versus -197.3 +/- 105.0% min). In all subgroups defined by habitual physical activity the mean % fall in FEV1 decreased more after treadmill exercise than after the step test. After step test and treadmill exercise no significant correlation was found between % fall in FEV1 and baseline lung function, or between % fall in FEV1 among groups defined by habitual physical activity. Although the 3-min step test yields a lower % fall in forced expiratory volume in one second (FEV1) and a lower value of the area above the FEV1 curve than treadmill testing, it is a quick, economical, reproducible and portable alternative procedure for identifying exercise-induced asthma in outpatients and epidemiological studies. Baseline lung function and habitual physical activity have no influence on the amount or duration of exercise-induced asthma.     

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.     

Spotlight on montelukast in asthma in children 2 to 14 years of age

Montelukast is a cysteinyl leukotriene receptor antagonist which is used as a preventive treatment for persistent asthma in patients > or =2 years of age. In children aged 6 to 14 years montelukast (5 mg/day) treatment resulted in a significant increase in FEV1 (forced expiratory volume in 1 second, primary clinical outcome) during an 8-week randomized, double-blind trial. Moreover, significant improvements were observed for a range of secondary endpoints assessing symptoms, exacerbation rates, beta-agonist usage and quality of life. Concomitant administration of montelukast (5 mg/day) and inhaled budesonide (200 microg twice daily) resulted in a trend towards an increase in FEV1 (p=0.06, primary endpoint) and a statistically significant reduction in both as-needed beta2-agonist usage and the percentage of days with asthma exacerbations compared with budesonide plus placebo. No significant differences were observed in asthma-related quality of life between the two groups. During clinical trials both improvements in lung function and reductions in as-needed beta2-agonist usage were generally observed within 1 day after initiation of therapy in children 2 to 14 years of age with persistent asthma. Data from a randomized, nonblind trial in 6- to 11-year-old children and a 6-month extension to this trial suggest that both compliance to therapy and patient satisfaction are greater for montelukast than for either inhaled cromolyn sodium (sodium cromoglycate) or inhaled beclomethasone. In addition, patients and parents preferred oral montelukast over cromolyn sodium. In 2- to 5-year-old children with persistent asthma, montelukast (4 mg/day) treatment resulted in significant improvements in a range of outcomes, such as as-needed beta2-agonist usage, symptom scores and percentage of days with asthma symptoms, as assessed during a randomized, double-blind trial primarily designed to assess tolerability. Data from small randomized, double-blind trials suggest that montelukast reduces exercise-induced bronchoconstriction in 6- to 14-year-old children. Montelukast is generally well tolerated. The frequency of adverse events in montelukast-treated children of all ages was comparable to that in patients receiving placebo. CONCLUSION: Oral montelukast has shown efficacy as a preventive treatment for asthma during clinical trials in children aged 2 to 14 years. The drug offers benefits over more standard therapies such as inhaled cromolyn sodium and nedocromil in terms of compliance and convenience. In addition, the drug offers significant benefits when added to inhaled corticosteroids (according to secondary endpoints). Montelukast offers an effective, well tolerated and convenient treatment option for children with asthma.     

The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma.

Effective treatment of respiratory symptoms, airway inflammation and impairment of lung function is the goal of any asthma therapy. Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children, its efficacy in infants and young children is not well known. The aim of this study was to investigate its effect in infants and young children with early childhood asthma. In a prospective randomised double-blind placebo-controlled study, 24 young children (10-26 months) with wheeze, allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were randomised to receive montelukast 4 mg or placebo. The forced expiratory volume in 0.5 seconds (FEV0.5) was measured using the raised volume rapid thoracic compression technique, and fractional exhaled nitric oxide (FeNO) and symptom scores were determined. No change was noted in FEV0.5, FeNO or symptom score in the placebo group following the treatment period. In contrast, significant improvements in mean+/-SD FEV0.5 (189.0+/-37.8 and 214.4+/-44.9 mL before and after treatment, respectively), FeNO (29.8+/-10.0 and 19.0+/-8.5 ppb) and median symptom score (5.5 and 1.5) were noted following treatment with montelukast. In conclusion, montelukast has a positive effect on lung function, airway inflammation and symptom scores in very young children with early childhood asthma.     

Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma

BACKGROUND: Previous research has shown that diet can modify the bronchoconstrictor response to exercise in asthmatic subjects. OBJECTIVE: Determine the effect of ascorbic acid supplementation on pulmonary function and several urinary markers of airway inflammation in asthmatic subjects with exercise-induced bronchoconstriction (EIB). METHODS: Eight asthmatic subjects with documented EIB participated in a randomized, placebo controlled double-blind crossover trial. Subjects entered the study on their usual diet and were placed on either 2 weeks of ascorbic acid supplementation (1500 mg/day) or placebo, followed by a 1-week washout period, before crossing over to the alternative diet. Pre- and post-exercise pulmonary function, asthma symptom scores, fraction of exhaled nitric oxide (FENO), and urinary leukotriene (LT) C4-E4 and 9alpha, 11beta-prostagladin (PG) F2] were assessed at the beginning of the trial (usual diet) and at the end of each treatment period. Results: The ascorbic acid diet significantly reduced (p < 0.05) the maximum fall in post-exercise FEV1 (-6.4 +/- 2.4%) compared to usual (-14.3 +/- 1.6%) and placebo diet (-12.9 +/- 2.4%). Asthma symptoms scores significantly improved (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. Post-exercise FENO, LTC4-E4 and 9alpha, 11beta-PGF2 concentration was significantly lower (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. CONCLUSION: Ascorbic acid supplementation provides a protective effect against exercise-induced airway narrowing in asthmatic subjects.     

Leukotriene receptor antagonists: efficacy and safety in children with asthma

To date, only one study of chronic use of a leukotriene receptor antagonist in children has been published. The efficacy and safety of montelukast in children 6-14 years of age with asthma (n = 336) was studied during an 8-week, double-blind, placebo-controlled trial. There was significantly greater improvement in forced expired volume in 1 sec (FEV(1)) from baseline for the montelukast group (8. 23%) compared to the placebo group (3.58%). There was a significant decrease in use of beta agonists for symptom relief and a significant decrease in the percentage of days and percentage of patients with asthma exacerbations. An asthma-specific quality of life questionnaire revealed significant overall improvement in quality of life and significant improvement in the quality of life domains for symptoms, activity, and emotions. Adverse effects were not significantly different for montelukast than for placebo, with the exception of allergic rhinitis which was more prevalent in the placebo group. A 6-month open follow-up of patients from the above study was undertaken. Effects of montelukast on FEV(1) were consistent over the 6 months, with the increase in FEV(1) not significantly different from a small control group treated with beclomethasone. Quality of life remained significantly improved throughout the open treatment period. In conclusion, leukotriene receptor antagonists are of value for the treatment of children with asthma.     

Exhaled nitric oxide and exercise-induced bronchospasm assessed by FEV1, FEF25-75% in childhood asthma.

The relationship between exhaled nitric oxide (eNO) and bronchial hyperresponsiveness (BHR) should be clarified. The aim of this study was to determine the relationship between eNO and exercise-induced bronchospasm (EIB) by estimation of the each lung parameter in asthmatic children who performed a bicycle ergometer exercise test. Twenty children with asthma were recruited. eNO concentration was examined by the recommended online method. To evaluate BHR, an exercise stress test was performed on a bicycle ergometer. The mean baseline eNO value was significantly correlated with the mean maximum % fall in forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25% and 75% (FEF25-75%) after exercise (r=0.53, r=0.65, respectively). eNO in the EIB-positive group was significantly higher than that in the EIB-negative group by assessing FEV1, FEF25-75% (p<0.005, p=0.005). We demonstrated that the most important lung parameter assessed the occurrence of EIB by a bicycle ergometer exercise test was not only FEV1 but FEF25-75%, which significantly correlated with eNO. This suggests that not only FEV1 but FEF25-75% can be used to evaluate the correlations between BHR (EIB) and airway inflammation (eNO) in asthmatic children. A low eNO is useful for a negative predictor for EIB.     

NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukast.

Nitric oxide in exhaled air (FENO) is increased in asthmatic children, probably reflecting aspects of airway inflammation. We have studied the effect of the leukotriene receptor antagonist (LTRA) montelukast on FENO with a view to elucidate potential anti-inflammatory properties of LTRAs. Twenty-six asthmatic children 6 to 15 yr of age completed a double-blind crossover trial of 2 wk of treatment with 5 mg montelukast once daily versus placebo. FENO was measured during single-breath exhalation at a constant flow rate of 0.1 to 0.13 L/s against a resistance of 10 kPa/L/s. Eleven children were receiving maintenance treatment with inhaled steroids during the study (mean daily dose, 273 microgram), whereas the other 15 used only inhaled beta(2)-agonists as required. The within-subject coefficient of variation of FENO over a 2-wk interval for the 26 children was 38%. FENO was significantly reduced by 20% after the 2-wk treatment with montelukast as compared with placebo as well as compared with baseline. This effect occurred rapidly with a 15% fall in FENO within 2 d. The effect of montelukast on FENO was independent of concurrent steroid treatment. The effect on FENO is probably not caused by bronchodilatation since FENO increased significantly after inhalation of terbutaline. In conclusion, FENO in asthmatic children was significantly decreased from montelukast, which corroborates anti- inflammatory properties of LTRA.     

Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma

It has been suggested that airway eosinophilic inflammation is associated with the severity of exercise-induced bronchospasm (EIB). Blood eosinophils are known to be an indirect marker of airway inflammation in asthma. The aim of this study is to investigate that a simple and easy blood test for blood eosinphil counts may predict the severity of EIB in asthma. Seventy-seven men with perennial asthma (age range 18-23 years) were included. Lung function test, skin prick test, and blood tests for eosinophils counts and total IgE levels were performed. Methacholine bronchial provocation test and, 24 h later, free running test were carried out. EIB was defined as a 15% reduction or more in post-exercise FEV1 compared with pre-exercise FEV1 value. Atopy score was defined as a sum of mean wheal diameters to allergens. EIB was observed in 60 (78%) of 77 subjects. Asthmatics with EIB showed significantly increased percentages of eosinophils (P<0.01), log eosinophil counts (P<0.001), and atopy scores (P<0.05) and decreased log PC20 values (P < 0.05) compared with asthmatics without EIB. Asthmatics with eosinophils of > 700 microl(-1) (36.9 +/- 12.7%) had significantly greater maximal % fall in FEV1 after exercise than asthmatics with eosinophils of < 350 microl(-1) (24.7 +/- 16.6%, P <0.05). Blood eosinophil counts > 350 microl(-1) yielded the specificity of 88% and positive predictive value of 93% for the presence of EIB.When a multiple regression analysis of maximal % fall in FEV1 according to log eosinophil counts, log PC20, log IgE and atopy score was performed, only blood eosinophil counts were significant factor contributing to the maximal % fall in FEV1 after exercise. These findings not only suggest that a simple blood test for eosinophils may be useful in the prediction of the severity of EIB, but also reinforce the view that airway eosinophilic inflammation may play a major role in EIB in asthma.