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     

Efficacy Response of Inhaled HFA-Albuterol Delivered via the Breath-Actuated Autohaler™ Inhalation Device Is Comparable to Dose in Patients with Asthma

Handling difficulties, such as poor coordination of actuation and inhalation, are common in patients using press and breathe (P&Bs) metered-dose inhalers to administer asthma medication. Although spacers can help overcome some difficulties, the cumbersome nature of these devices often detracts from their use for the administration of rescue medications, where portability is important. This randomized, placebo-controlled, multicenter, crossover study investigated the efficacy, dose-response and safety of HFA-albuterol delivered via a breath-actuated Autohaler inhalation device in comparison with the same medication delivered using a conventional P&B device. In total, 39 patients received six study treatments in a random sequence at clinic visits separated by 2-7 days: 2 puffs from a HFA-placebo Autohaler; 1, 2, or 4 puffs from a HFA-albuterol Autohaler; 1 or 2 puffs from a HFA-albuterol P&B. Both active inhalers delivered 90 µg albuterol base equivalent/actuation from the actuator. The change from baseline in forced expiratory volume in 1 s (FEV₁) and the area under the FEV₁ curve (FEV₁ AUC) were significantly greater than placebo for all active treatment groups (p ≤ 0.01) and were suggestive of a dose response for each inhaler. Examination of the pooled slope of the dose responses for the Autohaler and P&B using Finney's Parallel Line Bioassay Methodology found a highly statistically significant relationship indicating the equivalence of the two inhalers on both parameters (p ≤ 0.002). The relative potency of the two inhalers was 0.8 (95% CI: 0.47, 1.46) for the mean change from baseline in FEV₁ and 0.9 (95% CI, 0.56, 1.48) for the change from baseline in FEV₁ AUC. There was also a trend toward an increase in the mean percentage change from baseline in FEV₁ as the number of puffs increased for both inhalers. Furthermore, there were no significant differences between the treatment groups with regard to time to onset of bronchodilator effect and the duration of effect was significantly greater than placebo (p ≤ 0.01) in each of the active groups. Adverse events were generally mild to moderate in nature and were of similar incidence (≤18% of patients) in each group. This study demonstrates a dose-response for HFA-albuterol on bronchodilation using both the Autohaler and P&B devices and illustrates that, in patients with good coordination of inhalation with actuation, the efficacy and safety of the two inhalers is similar at equivalent doses.     

Cardiopulmonary Exercise Testing in Children and Adolescents with Asthma Who Report Symptoms of Exercise-Induced Bronchoconstriction

Patients with asthma often report symptoms of exercise-induced bronchoconstriction. We performed cardiopulmonary exercise testing to establish the cause of exercise limitation in patients with asthma, under treatment, who reported symptoms of exercise-induced bronchoconstriction. Ten of the 42 patients meeting criteria for inclusion in our study (24%) developed exercise-induced bronchoconstriction. Exercise limitation without exercise-induced bronchoconstriction was found in both obese and non-obese patients, suggesting that poor fitness is a problem independent of body habitus. Including cardiopulmonary exercise testing in the management of children with suspected exercise-induced bronchoconstriction would provide a better understanding of the etiology of their symptoms and facilitate more appropriate treatment.     

Cardiopulmonary Exercise Testing in Children and Adolescents with Asthma Who Report Symptoms of Exercise-Induced Bronchoconstriction

Patients with asthma often report symptoms of exercise-induced bronchoconstriction. We performed cardiopulmonary exercise testing to establish the cause of exercise limitation in patients with asthma, under treatment, who reported symptoms of exercise-induced bronchoconstriction. Ten of the 42 patients meeting criteria for inclusion in our study (24%) developed exercise-induced bronchoconstriction. Exercise limitation without exercise-induced bronchoconstriction was found in both obese and non-obese patients, suggesting that poor fitness is a problem independent of body habitus. Including cardiopulmonary exercise testing in the management of children with suspected exercise-induced bronchoconstriction would provide a better understanding of the etiology of their symptoms and facilitate more appropriate treatment.     

Community Study Using a Polymerase Chain Reaction Panel to Determine the Prevalence of Common Respiratory Viruses in Asthmatic and Nonasthmatic Children

We developed a sensitive polymerase chain reaction (PCR) panel, suitable for the detection of seven common respiratory viruses, to study the prevalence of viruses in nasal swabs obtained from clinically stable asthmatic children (n = 21), non-physician diagnosed asthmatic children with exercise-induced bronchoconstriction (EIB) (n = 16), and nonasthmatic, non-EIB controls (n = 33). The PCR panel detected viruses in 43/70 (61.4%) specimens but there were no significant differences in prevalence of these viruses between the three groups of children. These results indicate that clinically stable asthmatic and nonasthmatic children frequently harbor viruses in the upper respiratory tract.     

运动与运动诱发支气管痉挛的关系

运动与运动诱发支气管痉挛（exerciseinducedbronchoconstriction,EIB）的关系错综复杂,缺乏运动的生活方式有可能是EIB的易患因素,不恰当的过度运动容易导致EIB的发生,低一中等强度的有氧运动及热身运动有可能成为EIB的非药物治疗方法。深入研究不同运动与EIB的关系及其机制,对于EIB的筛查及治疗有重要的意义。     

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.     

间接激发试验诊断运动诱发性支气管痉挛

运动诱发性支气管痉挛（exercise-induced bronchoconstriction,EIB）是由运动诱发的急性短暂的气道缩窄。在运动员中的发病率约3％～13％,诊断EIB需要肺功能下降的客观依据,间接气道激发试验是常用于诊断EIB的肺功能检查,本文就一些国际上认可的间接气道激发试验的方法及判断标准做一综述。     

Determinants of the Severity of Exercise-Induced Bronchoconstriction in Patients with Asthma

Aim. In examining the mechanisms of exercise-induced bronchoconstriction (EIB), it is important to determine which factors most strongly affect the severity of EIB. We determined such factors in patients with asthma by stepwise multiple-regression analysis. Methods. Twenty-three patients with asthma underwent pulmonary function tests, methacholine provocation test, and sputum induction. Eosinophilic inflammatory indices and airway vascular permeability index (ratio of albumin concentrations in induced sputum and serum) were examined in sputum samples, and then an exercise test was performed by all asthmatics. Results. There was a significant correlation between the severity of EIB and degree of eosinophilic inflammation in induced sputum. Moreover, there was a significant correlation between the severity of EIB and airway vascular permeability index. Although we could not find a significant correlation between the severity of EIB and 1-sec forced expired volume, 20% provocation concentration of (PC₂₀) methacholine tended to be correlated with the severity of EIB. By stepwise multiple-regression analysis, we also found that airway vascular permeability index, eosinophil cationic protein levels in sputum, and PC₂₀ methacholine are independent predictors of the severity of EIB. Conclusion. We found that airway vascular hyperpermeability, eosinophilic inflammation, and bronchial hyperreactivity are independent factors predicting the severity of EIB.     

Prevalence Rate of Exercise-Induced Bronchoconstriction in Annaba (Algeria) Schoolchildren

Background. We studied the prevalence rate of exercise-induced bronchoconstriction (EIB) in Annaba schoolchildren. No previous assessment of this syndrome had ever been done in Algeria. Methods. EIB was evaluated using the 6 min free running test (6MFRT) on 286 children, 87.4% of whom were 10–12 years old. They performed the test in the morning, during the autumn–winter season. Peak expiratory flow rate (PEFR) was measured before, and then 5 and 10 min after the 6MFRT, a 15% or more decrease in post-exercise PEFR being defined as significant. Results. EIB was much more frequent in asthmatic than in nonasthmatic children (47.0% vs. 13.9%, p < .001) and the drop in PEFR was more marked among the former. EIB was observed more often in a cool temperature (<8°C). There were relatively more children who were either eutrophic or overweight among those presenting an EIB. Past histories of nocturnal wheezing and rhinoconjunctivitis presented respectively the best specificity (96.7%) and sensitivity (84.8%). Children of unemployed workers presented the highest occurrence of EIB. Passive smoking appeared as the only factor being related to EIB among the indoor pollutants. The prevalence rate of asthma (6.7%) was higher than in a previous cross-sectional epidemiological survey study performed in the Maghreb. The prevalence rate of EIB (13.9%) was situated in the upper range of the results given worldwide. Conclusions. These features of a fairly high bronchial hyperresponsiveness could be facilitated by the polluted environment of the city.     

Switching Patients with Asthma from Chlorofluorocarbon (CFC) Albuterol to Hydrofluoroalkane-134a (HFA) Albuterol

Chlorofluorocarbon (CFC) propellants deplete stratospheric ozone. Production and use of CFCs, except for certain critical exemptions, has been prohibited by the Montreal Protocol. Use of CFCs as propellants in metered-dose inhalers (MDIs) is still allowed, but the U.S. Food and Drug Administration is planning the transition to alternative propellants for use in MDIs. Hydrofluoroalkane-134a (HFA), a non-ozone-depleting propellant, has been used to reformulate albuterol (HFA albuterol). This study evaluates whether comparable safety and efficacy continues for 12 weeks after patients with asthma are switched from CFC albuterol to HFA albuterol. Patients with asthma stabilized on CFC albuterol during a 12-week safety and efficacy trial were randomized to either continue receiving CFC albuterol or to be switched to receive HFA albuterol in a yearlong safety and efficacy trial. Safety and efficacy were compared over the first 12 weeks of the yearlong trial between patients who had remained on CFC albuterol and those who had been switched to HFA albuterol. Bronchodilator efficacy was evaluated by serial spirometry for 6 hr after the patients self-administered the study drug in the clinic. Safety was assessed by measuring changes in pulse rate, blood pressure, and electrocardiogram (ECG) intervals after dosing with study drug, monitoring adverse events, and performing prestudy and poststudy laboratory testing and physical examinations. No significant differences in bronchodilator efficacy between the patients continuing to receive CFC albuterol and those switched to HFA albuterol were found in the 12 weeks after the switch. No differences between the two products were found for changes in pulse rate, blood pressure, and ECG intervals. Adverse event profiles were similar for the two products, except the patients remaining on CFC albuterol reported increased asthma symptoms and rhinitis significantly more often than the patients switched to HFA albuterol. No clinically meaningful changes in laboratory tests or physical examinations were found in either treatment group. Patients with asthma switched from CFC albuterol to HFA albuterol receive comparable bronchodilation with a similar safety profile as those continuing to receive CFC albuterol.     

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 β₂-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 × 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 × FEV₁) to VEmax. VEmax was 99 ± 11% of predicted MVV (35 × FEV₁) and was positively related (r = 0.85, p ≤ 0.05). TV was 88 ± 9% of VEmax (range: 64-109). For elite athletes, the high variability in 30 × 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.     

Efficacy Response of Inhaled HFA-Albuterol Delivered via the Breath-Actuated Autohaler™ Inhalation Device Is Comparable to Dose in Patients with Asthma

Handling difficulties, such as poor coordination of actuation and inhalation, are common in patients using press and breathe (P&Bs) metered-dose inhalers to administer asthma medication. Although spacers can help overcome some difficulties, the cumbersome nature of these devices often detracts from their use for the administration of rescue medications, where portability is important. This randomized, placebo-controlled, multicenter, crossover study investigated the efficacy, dose-response and safety of HFA-albuterol delivered via a breath-actuated Autohaler inhalation device in comparison with the same medication delivered using a conventional P&B device. In total, 39 patients received six study treatments in a random sequence at clinic visits separated by 2–7 days: 2 puffs from a HFA-placebo Autohaler; 1, 2, or 4 puffs from a HFA-albuterol Autohaler; 1 or 2 puffs from a HFA-albuterol P&B. Both active inhalers delivered 90 µg albuterol base equivalent/actuation from the actuator. The change from baseline in forced expiratory volume in 1 s (FEV₁) and the area under the FEV₁ curve (FEV₁ AUC) were significantly greater than placebo for all active treatment groups (p ≤ 0.01) and were suggestive of a dose response for each inhaler. Examination of the pooled slope of the dose responses for the Autohaler and P&B using Finney's Parallel Line Bioassay Methodology found a highly statistically significant relationship indicating the equivalence of the two inhalers on both parameters (p ≤ 0.002). The relative potency of the two inhalers was 0.8 (95% CI: 0.47, 1.46) for the mean change from baseline in FEV₁ and 0.9 (95% CI, 0.56, 1.48) for the change from baseline in FEV₁ AUC. There was also a trend toward an increase in the mean percentage change from baseline in FEV₁ as the number of puffs increased for both inhalers. Furthermore, there were no significant differences between the treatment groups with regard to time to onset of bronchodilator effect and the duration of effect was significantly greater than placebo (p ≤ 0.01) in each of the active groups. Adverse events were generally mild to moderate in nature and were of similar incidence (≤18% of patients) in each group. This study demonstrates a dose-response for HFA-albuterol on bronchodilation using both the Autohaler and P&B devices and illustrates that, in patients with good coordination of inhalation with actuation, the efficacy and safety of the two inhalers is similar at equivalent doses.     

Effect of Desloratadine on Patients with Allergic Rhinitis and Exercise-Induced Bronchoconstriction: A Placebo Controlled Study

Background. Exercise induced broncho-constriction (EIB) is a significant problem in asthmatic patients. The link between allergic rhinitis and asthma is now well established. Patients with allergic rhinitis may have EIB. Objective. This study compared the effects of desloratadine and placebo on EIB in a group of patients with allergic rhinitis and EIB. Methods. This was a double blind placebo controlled, randomized, crossover study. Exercise challenge tests were performed before and after 7 days of treatment with either 5 mg desloratadine or placebo. Patients then underwent a washout period for 7 days and were crossed over to receive either 5mg desloratadine or placebo. The exercise challenge tests were repeated. Results. Desloratadine had no effect on the reduction in percentage fall in FEV₁, the AUC (0–60 min) and the time to recovery. Conclusions. Desloratadine has no effect in attenuating the broncho-constriction caused by exercise in patients with allergic rhinitis and exercise induced broncho-constriction. Clinical implications. Patients with allergic rhinitis and exercise induced broncho-constriction must be treated with either a ß₂-agonist or LRTA for relief or prophylaxis of their EIB. Capsule Summary. Desloratadine does not have an effect on exercise induced bronchoconstriction. Patients with allergic rhinitis with exercise induced bronchoconstriction who are on desloratadine will still require treatment with ß₂ agonist or leukotriene receptor antagonist for their symptoms.     

Effects of inspired air conditions on catecholamine response to exercise in asthma

The influence of different inspired air conditions on exercise-induced bronchoconstriction (EIB) is well appreciated. However, the mechanism by which this influence is exerted is uncertain. To determine if varied inspired air conditions during exercise could affect the catecholamine response to physical exercise, we had 13 asthmatic and 6 healthy children (aged 10–18 years) undergo two bouts of cycle ergometry tests under different air conditions. One test was done while breathing cold dry (CD) air (temperature, ?20.2°C; relative humidity, 0%) and the other while breathing warm humid (WH) air (temperature, 34.3%; relative humidity, 100%). Forced expiratory volume in 1 second (FEV,) and plasma catecholamine concentrations were recorded before and after exercise. Marked EIB (48 2 5% SEM fall in FEV, from baseline) developed in all asthmatics after the CD exercise, but no EIB was noted after the WH exercise. Normal controls had no EIB under either test conditions. Plasma levels of catecholamines at rest, and the changes that occurred during and after exercise, were comparable within as well as between the groups in both tests. Catecholamines did not rise in asthmatics following development of EIB. These data demonstrate that inspired air conditions do not influence the sympathoadrenal response to exercise, at least as reflected in plasma catecholamine levels. In fact, this response did not differ between asthmatics and normals, irrespective of the development of EIB. These results are consistent with previous reports about impaired catecholamine response of asthmatics to bronchoconstriction. Pediatr Pulmonol. 1994;18:99–103. © 1994 Wiley-Liss, Inc.     

Dietary Omega-3 Polyunsaturated Fatty Acid Supplementation and Airway Hyperresponsiveness in Asthma

Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20-25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.     

Dietary Omega-3 Polyunsaturated Fatty Acid Supplementation and Airway Hyperresponsiveness in Asthma

Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20–25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.     

硫酸沙丁胺醇治疗支气管哮喘疗效观察

目的探讨硫酸沙丁胺醇治疗支气管哮喘的临床疗效。方法选择支气管哮喘患者60例,随机分为观察组和对照组各30例,观察组给予硫酸沙丁胺醇治疗,对照组给予布地奈德治疗,比较两组患者的治疗效果。结果观察组和对照组的总有效率分别为100%和83.33%,观察组疗效明显优于对照组,差异有统计学意义(P<0.05)。结论硫酸沙丁胺醇治疗支气管哮喘,能显著改善哮喘症状,改善肺功能,临床疗效较好,且无明显不良反应,值得临床推广。