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.     

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。     

Applicability of interrupter resistance measurements for evaluation of exercise-induced bronchoconstriction in children

The interrupter technique is a noninvasive method for measuring air-flow resistance during tidal breathing. This method requires minimal cooperation, and is therefore promising for use in uncooperative children. The aim of this study was to evaluate applicability interrupter resistance (Rint) measurements in the assessment of exercise-induced bronchoconstriction (EIB). Fifty children aged 5-12 years with mild to moderate asthma were tested by exercise challenge, consisting of free outdoor running for 6 min at 80-90% of maximal predicted heart rate for age. Rint, forced expiratory volume in 1 sec (FEV1), and peak expiratory flow (PEF) were measured before and 10 min after exercise. EIB was defined as a fall of 10% or more in FEV1 after exercise. The repeatability of Rint was assessed, and its response to exercise challenge was compared with current standardized methods. The mean intermeasurement coefficient of variation was 4.6% (SD, +/- 3.0%), and the repeatability coefficient was 0.056 kPa/l/sec. Eighteen (36%) of the 50 children had EIB after exercise challenge test. The area under the receiver-operating characteristic (ROC) curve was 0.953 (95% confidence interval, 0.853-0.992; P < 0.001), and the optimal Rint cutoff value was 15.2%, producing a sensitivity of 88.9% and a specificity of 96.9%. The positive and negative predictive values were 94.1% and 93.9%, respectively. The kappa value between FEV1 and Rint was 0.83. The repeatability of Rint measurements was good, and the results of exercise challenge tests using Rint measurements have excellent agreement with the current standardized methods to detect EIB. Considering that only minimal comprehension and coordination are needed without forced breathing technique, the Rint measurement can provide a useful alternative for assessment of EIB in children unable to perform reliable spirometry.     

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.     

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.     

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     

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     

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.     

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.     

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.     

Mannitol as a challenge test to identify exercise-induced bronchoconstriction in elite athletes

Bronchial provocation tests provide objective criteria for asthma and exercise-induced bronchoconstriction (EIB) and were recommended to justify the use of inhaled beta2-agonists by athletes at the Winter Olympics 2002. Eucapnic voluntary hyperpnea (EVH) was one test recommended to identify EIB. Provocation with EVH requires a special dry gas mixture limiting its availability. Provocation tests with osmotic aerosols require less expensive equipment that is easily portable. We assessed the sensitivity of a challenge with mannitol to identify responsiveness to EVH in 50 elite summer sport athletes who were unselected if they had respiratory symptoms. Asthma was previously diagnosed by a doctor in 27 subjects, and 21 subjects were currently under treatment for EIB or asthma. The mean predicted FEV1 was 103.6 +/- 10.8%, FVC was 99 +/- 13.3%, and mean forced expiratory flow during the middle half of the FVC was 104 +/- 22.7%. A total of 25 subjects were positive to EVH challenge (mean percentage of fall in FEV1 was 25.4 +/- 15% SD), and 26 subjects had a positive mannitol challenge (geometric mean [95% confidence interval] provoking dose causing a 10% fall in forced expiratory volume in one second [PD10] was 202 mg [134, 300], with 24 of the subjects positive to both challenges). Mannitol had a sensitivity of 96% and specificity of 92% to identify a positive response to EVH and, as such, could be used as an alternative to EVH to identify EIB.     

The prevalence of exercise-induced bronchospasm in soccer player children, ages 7 to 16 years

This study represents an attempt to determine the prevalence of exercise-induced bronchospasm among soccer player children. A total of 234 soccer player boys of all soccer schools from Shahr-Rey enrolled in this study. They did not have any history of a recent or chronic respiratory tract disease, a history of allergic diseases, and history of bronchodilator drugs consumption during the 24 hours prior to the study. Pulmonary function test (PFT) was performed for each participant before exercise and 6 and 15 minutes after playing soccer. The diagnosis of EIB was by a decrease in forced expiratory volume in 1 second (FEV1) by at least 10% and in peak expiratory flow rate (PEFR) by at least 15% with exercise challenge. If there was reduction in one parameter alone, the participants were considered as prone to EIB. Considering both FEV1 and PEFR the prevalence of EIB was 2.1% and 18.4% were prone to EIB. If FEV1 or PEFR tests were used as criteria for diagnosis of airway obstruction, the prevalence of EIB would be 6% and 15.8%, respectively. There was no significant difference between the post of players, family history of allergic disease and EIB in soccer players. This study suggests that at least 2.1% of soccer players will develop bronchospasm even if they do not have any history of asthma and allergy.     

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.     

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.     

Vascular involvement in exercise-induced airway narrowing in patients with bronchial asthma

STUDY OBJECTIVES: The bronchial microcirculation has the potential to contribute to the pathophysiologic mechanisms of exercise-induced bronchoconstriction (EIB) in asthmatic patients. This study was designed to determine whether increase in airway vascular permeability is associated with the severity of EIB in asthmatic patients. DESIGN: Cross-sectional analysis. SETTING: University hospital. PARTICIPANTS: Twenty-five asthmatic patients and 12 normal control subjects. INTERVENTIONS: All asthmatics performed an exercise test, and the percentage of maximal fall in FEV(1) and the area under the curve of the percentage fall in FEV(1) plotted against time for 30 min (AUC(0-30)) were determined. MEASUREMENTS AND RESULTS: The inflammatory indexes, NO levels, and airway vascular permeability index (ratio of albumin concentrations in induced sputum and serum) were examined in all subjects. The airway vascular permeability index was significantly higher in EIB-positive asthmatics (0.031 +/- 0.009) than in EIB-negative asthmatics (0.020 +/- 0.005, p = 0.0011) and normal control subjects (0.008 +/- 0.003, p < 0.0001). We also found that there was a significant correlation between NO levels in induced sputum and the airway vascular permeability index (r = 0.525, p = 0.0101). Moreover, the airway vascular permeability index was significantly correlated with the severity of EIB (percentage of maximal fall in FEV(1) [r = 0.761, p = 0.0002], AUC(0-30) [r = 0.716, p = 0.0005]). However, this index was not significantly correlated with magnitude of eosinophilic inflammation. CONCLUSION: Our findings suggest that increased airway vascular permeability due to excessive production of NO correlates with the severity of EIB in asthmatics, and that assessment of albumin flux in airway lining fluid stimulated by hypertonic saline solution is a sensitive predictor of the severity of EIB.     

Acceptability, reproducibility, and sensitivity of forced expiratory volumes and peak expiratory flow during bronchial challenge testing in asthmatic children.

OBJECTIVES: To compare the acceptability, reproducibility, and sensitivity of spirometric outcome measures of airway caliber during challenge testing in children. DESIGN: FEV(1), forced expiratory volume in 0.75 s, forced expiratory volume in 0.5 s, and peak expiratory flow (PEF) were recorded during stepwise dosimetric histamine challenge tests. The responses were compared, and the reproducibility at baseline and from duplicate measurements at each challenge step was determined. PATIENTS: One hundred five children with newly diagnosed asthma, aged 5 to 10 years. RESULTS: Compared to PEF, FEV(1) showed better baseline reproducibility (p = 0.002) and higher sensitivity (p < 0.0001) during challenge testing, determined as the change normalized to the baseline variation, while the forced expiratory volumes were not significantly different in these respects. During challenge testing in subjects with acceptable flow-volume tracings, paired recordings of FEV(1) agreed within 0.1 L in 85% and within 0.2 L in 93% of measurements. During challenge testing, the reproducibility of FEV(1) measurements was not better than that of the other indexes. Failure to exhale long enough precluded the use of FEV(1) in 16 of the children, particularly the youngest children. CONCLUSIONS: The results demonstrated that the recently published guidelines for FEV(1) measurements during challenge tests can be applied to children. During challenge tests in asthmatic children, the advantage of the shorter fractions of forced expiratory volume was that they were more often acceptably recorded than FEV(1), while they showed as good reproducibility and were also equally sensitive in assessing changes in airway obstruction.     

Inspiratory stridor in elite athletes

STUDY OBJECTIVES: Diagnosis and medical intervention for exercise-induced bronchospasm (EIB) are often based on self-reported symptoms, without spirometric confirmation. Inspiratory stridor (IS), a symptom of vocal cord dysfunction (VCD), is frequently mistaken for EIB wheeze. Athletes with exercise IS that spontaneously resolves on activity cessation are suspect for VCD and may not have EIB. This study estimated IS prevalence in elite athletes and determined its relationship to EIB. Subjects/methods: Three hundred seventy athletes (174 female and 196 male subjects) provided a medical history, and underwent spirometry before and after exercise challenge. Exercise challenges were conducted in cold, dry ambient conditions. EIB positive (EIB +) was defined as a > or = 10% postexercise fall in FEV(1). Athletes were monitored for IS during exercise; 78.4% of the athletes in this study (n = 290) were tested on multiple occasions. RESULTS: EIB was identified in 30% of 370 athletes tested (58 female and 53 male subjects). IS was observed in 5.1% (18 female and 1 male subjects) during exercise and spontaneously resolved in these subjects within 5 min after exercise cessation. Ten IS-positive (IS +) athletes (52.6%) were EIB +, and 8 of these athletes had a previous EIB diagnosis; however, beta(2)-agonist treatment resolved IS in only 2 subjects. Eight of nine IS +/EIB-negative (EIB -) athletes had a previous EIB diagnosis; seven subjects received beta(2)-agonist treatment with no IS resolution. Resting spirometric measurements did not distinguish IS, but postexercise mid-flow (FEF(50)/FIF(50)) ratio > 1.5 was more frequent (33%, p < 0.05) among IS + athletes. The FEF(50)/FIF(50) ratio was higher for IS +/EIB + athletes than for IS -/EIB + athletes (1.97 +/- 1.69 vs 0.81 +/- 0.39, p < 0.05). The postexercise fall in FVC was greater (p < 0.05) for IS +/EIB - athletes (9.2 +/- 5.0%) than for IS-negative (IS -) /EIB - athletes (5.3 +/- 4.3%). No difference in postexercise FEV(1) was identified between IS + and IS - athletes (within EIB + or EIB - groups). CONCLUSIONS: Five percent of athletes were IS +, with EIB comorbidity observed in 53% of these subjects. Misdiagnosis of IS as EIB is common. The lack of a beta(2)-agonist response in combination with postexercise serial spirometry can be useful in excluding solitary IS and confirming EIB diagnosis.     

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.     

Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline.

The onset of bronchoprotection as obtained by various beta2-agonists has not been examined in a comparitive study. In this study, the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting beta2-agonists formoterol and salmeterol and the short-acting beta2-agonist terbutaline were measured. Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction (mean baseline forced expiratory volume in one second (FEV1): 90% predicted; mean fall in FEV1 after exercise: 31% from baseline) were enrolled in this double-blind, double-dummy, placebo-controlled, randomized, four-period crossover study. Exercise challenges were performed on 12 days at either 5, 30, or 60 min after inhalation of a single dose of formoterol (12 microg Turbuhaler), salmeterol (50 microg Diskus), terbutaline (500 microg Turbuhaler) or placebo. Exercise-induced bronchoconstriction (maximum fall in FEV1 or area under the curve) did not differ significantly between terbutaline, formorerol and salmeterol either 5, 30, or 60 min after inhalation of the study medication. In contrast, the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol (p<0.05, each), which both showed a similar time course. At all time points between 5 and 60 min, formoterol provided significantly greater bronchodilation than salmeterol (p<0.05). These data indicate that equipotent doses of the bronchodilators salmeterol, formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction, despite the fact that the time course of bronchodilation was significantly different between the three beta2-agonists.     

An evaluation of standardizing target ventilation for eucapnic voluntary hyperventilation using FEV1.

Athletes are required to provide objective documentation of exercise-induced bronchoconstriction (EIB) to use beta2-agonists during Olympic competition. A positive response to bronchial provocation by eucapnic voluntary hyperventilation (EVH) is considered acceptable confirmation of EIB. Thirty times forced expiratory volume in the first second (FEV1) is recommended as EVH target ventilation (TV), an intensity intended to estimate 85% of maximal voluntary ventilation (MVV). There is a paucity of data examining the accuracy of predicting MVV from FEV1 in elite athletes. The purpose of this study was to evaluate the efficacy of 30 x FEV1 as standardized EVH TV. Maximal minute ventilation during exercise (VEmax) and pulmonary function of 78 elite winter athletes (25 males, 53 females; 25 EIB positive, 53 normal) were analyzed retrospectively. Adequacy and variability of the equation was ascertained by examining the ratio of EVH TV (30 x FEV1) to VEmax. VEmax was 99+/-11% of predicted MVV (35 x FEV1) and was positively related (r=0.85, p < or = 0.05). TV was 88+/-9% of VEmax (range: 64-109). For elite athletes, the high variability in 30 x FEV1 to standardize TV for EVH may result in under-diagnosis for low-end outliers. Since VEmax of elite endurance athletes is typically known (via maximal aerobic testing) we recommend 85% VEmax as a more accurate and reliable method to establish EVH TV for this group; if VEmax is not available, then 85% of measured MVV may be used.