Oil supplementation with a special combination of n-3 and n-6 long-chain polyunsaturated fatty acids does not protect for exercise induced asthma: a double-blind placebo-controlled trial.

BACKGROUND: Many patients suffering from exercise-induced asthma (EIA) have normal lung function at rest and show symptoms and a decline in FEV1 when they do sports or during exercise-challenge. It has been described that long-chain polyunsaturated fatty acids (LCPUFA) could exert a protective effect on EIA. METHODS: In this study the protective effect of supplementation with a special combination of n-3 and n-6 LCPUFA (sc-LCPUFA) (total 1.19 g/ day) were investigated in an EIA cold air provocation model. PRIMARY OUTCOME MEASURE: Decrease in FEV1 after exercise challenge and secondary outcome measure: anti-inflammatory effects monitored by exhaled NO (eNO) before and after sc-LCPUFA supplementation versus placebo. RESULTS: Ninety-nine patients with exercise-induced symptoms aged 10 to 45 were screened by a standardized exercise challenge in a cold air chamber at 4 °C. Seventy-three patients fulfilled the inclusion criteria of a FEV1 decrease > 15% and were treated double-blind placebo-controlled for 4 weeks either with sc-LCPUFA or placebo. Thirty-two patients in each group completed the study. Mean FEV1 decrease after cold air exercise challenge and eNO were unchanged after 4 weeks sc-LCPUFA supplementation. CONCLUSION: Supplementation with sc-LCPUFA at a dose of 1.19 g/d did not have any broncho-protective and anti-inflammatory effects on EIA. TRIAL REGISTRATION: Clinical trial registration number: NCT02410096. Registered 7 February 2015 at Clinicaltrial.gov.

Nonpharmacologic Strategies to Manage Exercise-Induced Bronchoconstriction.

Pharmacologic management of exercise-induced bronchoconstriction (EIB) is the mainstay of preventative therapy. There are some nonpharmacologic interventions, however, that may assist the management of EIB. This review discusses these nonpharmacologic interventions and how they may be applied to patients and athletes with EIB.

[Impact of exercise, sport and rehabilitation therapy in asthma and COPD]. / Impact von Bewegung, Sport und Rehabilitation bei Asthma und COPD.

Patients with chronic obstructive pulmonary disease (COPD) and Asthma share increased physical inactivity as a characteristic and risk factor for the aggravation of their symptoms and marker of their health condition, respectively. Physical inactivity may be objectively measured by means of accelerometry superior to questionnaires. Physical inactivity is the reason for a reduced endurance capacity and a reduction of strength with concomitant decrease of skeletal muscle mass aggravating inflammation as a common pathophysiologic soil. Endurance training is recommended in the form of continuous and interval training having similar effects on endurance capacity executed on either a bike or as walking in patients with COPD und Asthma. Walking inherits the potential additional benefit of a reduction of fall risk which needs additional scientific evidence. This holds true especially for elderly subjects. Strength training is important because of the frequently atrophied skeletal musculature, which triggers the increase of the exercise-induced ventilation by early lactate acidosis and thereby aggravates dyspnea during exercise. An important aspect of therapy is the maintenance of the individualized training after discharge from hospital in the domestic environment taking into consideration training facilities, encounter groups and social circumstances. The objective measurement of physical activity has the potential to guide and control therapy. Because of the frequently present cardio-metabolic comorbidities the assessment of the exercise capacity as well an evaluation of nutrition should be included into a holistic therapeutical approach. An optimized bronchospasmolytic and anti-inflammatory therapy is the basis for a sufficient response to exercise training. In patients with asthma, a warm-up phase of at least 15 min prior to exercise is recommended. Redundant fear of exercise-induced attacks of asthma shall be avoided by doing so. If necessary, additional psychological support should be given.

Is yoga training beneficial for exercise-induced bronchoconstriction?

BACKGROUND: Some studies have shown the beneficial effects of yoga for individuals with bronchial hyperreactivity with regard to (1) a reduction in the use of rescue medication, (2) an increase in exercise capacity, and (3) an improvement in lung function. Despite the fact that yoga is promising as a new treatment for pediatric patients, further studies are needed to assess the use of this training for asthma management. OBJECTIVE: This study was performed to assess the beneficial effects of yoga in exercise-induced bronchoconstriction (EIB) in children. DESIGN: The study was prospective, with no control group. Participants were randomly chosen among the new patients at the unit. SETTING: This study was conducted in the Erciyes University School of Medicine, Pediatric Allergy Unit, in Kayseri, Turkey. PARTICIPANTS: Two groups of asthmatic children aged 6-17 y were enrolled in the study: (1) children with positive responses to an exercise challenge (n = 10), and (2) those with negative responses (n = 10). INTERVENTION: Both groups attended 1-h sessions of yoga training 2 ×/wk for 3 mo. OUTCOME MEASURES: Researchers administered spirometric measurement to all children before and immediately after participating in an exercise challenge. This process was performed at baseline and at the study's end. Age, gender, IgE levels, eosinophil numbers, and spirometric measurement parameters including forced expiratory volume in 1 sec (FEV1), forced expiratory flow 25%-75% (FEF25%-75%), forced vital capacity (FVC), peak expiratory flow percentage (PEF%), and peak expiratory flow rate (PEFR) were compared using the Mann-Whitney U test and the Wilcoxon test. A P value < .05 was considered significant. RESULTS: At baseline, no significant differences were observed between the groups regarding demographics or pre-exercise spirometric measurements (P > .05, Mann-Whitney U test). Likewise, no significant differences in spirometric measurements existed between the groups regarding the change in responses to an exercise challenge after yoga training (P > .05, Wilcoxon test). For the exercise-response-positive group, the research team observed a significant improvement in maximum forced expiratory volume 1% (FEV1%) fall following the exercise challenge after yoga training (P > .05, Wilcoxon test). All exercise-response-positive asthmatics became exerciseresponse-negative asthmatics after yoga training. CONCLUSION: This study showed that training children in the practice of yoga had beneficial effects on EIB. It is the research team's opinion that yoga training can supplement drug therapy to achieve better control of asthma.

Advances in pediatric asthma in 2008: where do we go now?

This year's summary focuses on recent advances in pediatric asthma as reported in Journal publications in 2008. New National Asthma Education and Prevention Program asthma guidelines were released in 2007 with a special emphasis on asthma control. Attention was redirected to methods that could reduce impairment, specifically symptom control, and minimize risk, including exacerbations. Journal theme issues in 2008 focused on several relevant asthma topics including asthma exacerbations, exercise-induced bronchospasm, asthma and obesity, and occupational asthma. This review highlights Journal articles and related articles that reinforce principles of the guidelines and also direct us to new information that will advance asthma care for children. A major step forward will be finding ways to implement the asthma guidelines.

Long-acting beta 2-adrenoceptor agonists and exercise-induced asthma: lessons to guide us in the future.

The safety and efficacy of long-acting beta(2)-adrenoceptor agonists (LABAs) taken intermittently for the prevention of exercise-induced asthma (EIA) in children is well established. However, the safety and efficacy of LABAs taken twice daily, either alone or in combination with inhaled corticosteroids, for the prevention of EIA is not as clear because of issues of tolerance (defined as being less responsive to the influence of LABAs). There have been many observations on short-acting beta(2)-adrenoceptor agonists (SABAs) and EIA that should have alerted us to the potential for tolerance and desensitization to occur with LABAs. For example, we expected that the use of LABAs for EIA would overcome the problem of the short duration of protection of SABAs, and to some extent they have. The protective period of a LABA is two to three times longer in duration than that of a SABA. However, when a LABA is taken daily it is apparent that the duration of its protective effect is reduced and there is a risk of EIA occurring well within the 12-hour administration schedules. Furthermore, daily use of LABAs attenuates the bronchodilator effect of SABAs, an effect that is greater the more severe the bronchoconstriction. This 'tolerance' increases both the time and the amount of therapy that is needed to recover from bronchoconstriction, and thus, could potentially impact on the success of rescue therapy should severe EIA occur. The daily use of LABAs also increases the sensitivity of the bronchial smooth muscle to contractile agents. This increase in sensitivity is almost equivalent to the extent to which inhaled corticosteroids reduce sensitivity to the same contractile agents. The increased sensitivity to contractile agents may occur either by a reduction in the inhibitory effect of beta(2)-adrenoceptor agonists on release of mediators from mast cells or by a direct effect on the bronchial smooth muscle. These unwanted effects of LABAs are not necessarily reduced by concomitant treatment with inhaled corticosteroids. As the number of children being treated with LABAs increases, it is predicted that problems with breakthrough EIA will also increase. We need to know the percentage of children taking a LABA daily who are requiring either extra doses of a beta(2)-adrenoceptor agonist to prevent (or reverse) EIA or other provocative stimuli. If this percentage is significant then we may need to reconsider the position of LABAs in the treatment of children with asthma who regularly perform strenuous physical activity.

Albuterol HFA is as effective as albuterol CFC in preventing exercise-induced bronchoconstriction.

BACKGROUND: Secondary to the phase-out of chlorofluorocarbons (CFCs), the albuterol (Ventolin, GlaxoSmithKline, Uxbridge, Middlesex, United Kingdom) pressurized metered-dose inhaler (MDI) has been formulated in a non-ozone-depleting propellant, hydrofluoroalkane (HFA) 134a. OBJECTIVE: To compare the efficacy of albuterol HFA to albuterol CFC and placebo HFA in protecting patients from exercise-induced bronchospasm (EIB). METHODS: Randomized, double-blind, placebo-controlled, three-way crossover study in patients with documented EIB. Patients (n = 24) aged 18 to 45 years old received albuterol HFA or albuterol CFC, (total dose of 180 microg ex-actuator), or placebo HFA via an MDI, 30 minutes before a standardized exercise challenge. Serial forced expiratory volume in 1 second (FEV1) measurements were made 5 minutes before exercise and 5, 10, 15, 20, 25, 30, and 60 minutes postexercise. The primary outcome measure was the maximum percentage fall in FEV1 over the 60 minutes after exercise. RESULTS: The adjusted mean maximum percentage falls in FEV1 postexercise for albuterol HFA and CFC groups were 15.4% and 14.9%, respectively. The two formulations were comparable with a treatment difference of -0.5% (P = 0.848; 95% confidence interval, -5.3 to 4.4%). When compared with the fall in FEV1 for placebo (33.7%), both active treatments demonstrated a significantly smaller fall in FEV1 postexercise (P < 0.001). Safety profiles were similar among the three treatment groups. CONCLUSIONS: The results provide assurance to prescribers that the formulation of albuterol in the non-ozone-depleting propellant HFA 134a has not affected its efficacy in the treatment of EIB in asthmatic patients. Single doses of albuterol HFA and CFC from an MDI are comparable in terms of efficacy and safety on a microgram per microgram basis.

The effects of carbon dioxide on exercise-induced asthma: an unlikely explanation for the effects of Buteyko breathing training.

OBJECTIVES: To examine the effect of breathing 3% CO2 on exercise-induced asthma (EIA), as a raised airway CO2 level is suggested to mediate the effects of Buteyko breathing training (BBT). DESIGN: Double-blind crossover study, using a standard laboratory-based exercise challenge, with EIA defined as a fall of 15% or greater in the forced expiratory volume in one second (FEV1) within 30 minutes of completing a standard exercise protocol. SUBJECTS: 10 adults with confirmed EIA. INTERVENTION: Air enriched with 3% CO2 during and for 10 minutes after exercise. OUTCOME MEASURES: Maximum percentage fall in FEV1 after exercise. Area under curve (AUC) of the decrease in FEV1 with time. RESULTS: Mean maximum fall in FEV1 was similar: 19.9% with air, and 26.9% with 3% CO2 (P = 0.12). The mean AUC for the total 30-minute post-exercise period was 355 for air and 520 for 3% CO2 (P = 0.07). After discontinuing the 3% CO2 at 10 minutes after exercise, there was a further and sustained fall in FEV1. Mean AUC for the period 10-30 minutes post-exercise was significantly greater for CO2 than air (275 and 137, respectively [P = 0.02]). Mean minute ventilation was increased when subjects exercised breathing 3% CO2: 77.5 L/min for 3% CO2, compared with 68.7 L/min for air (P = 0.02). CONCLUSION: Breathing 3% CO2 during exercise does not prevent EIA. The shape of the FEV1 response curve after 3% CO2 suggests that a greater degree of EIA (because of increased minute ventilation during exercise) was opposed by a direct relaxant effect of CO2 on the airway. Increased airway CO2 alone is an unlikely mechanism for the reported benefits of BBT; nevertheless, further study of the effects of voluntary hypoventilation in asthma is warranted.

Keeping children with exercise-induced asthma active.

Exercise-induced bronchospasm, exercise-induced bronchoconstriction, and exercise-induced asthma (EIA) are all terms used to describe the phenomenon of transient airflow obstruction associated with physical exertion. It is a prominent finding in children and young adults because of their greater participation in vigorous activities. The symptoms shortness of breath, cough, chest tightness, and wheezing normally follow the brief period of bronchodilation present early in the course of exercise. Bronchospasm typically arises within 10 to 15 minutes of beginning exercise, peaks 8 to 15 minutes after the exertion is concluded, and resolves about 60 minutes later, but it also may appear during sustained exertion. EIA occurs in up to 90% of asthmatics and 40% of patients with allergic rhinitis; among athletes and in the general population its prevalence is between 6% and 13%. EIA frequently goes undiagnosed. Approximately 9% of individuals with EIA have no history of asthma or allergy. Fifty percent of children with asthma who gave a negative history for EIA had a positive response to exercise challenge.6 Among high school athletes, 12% of subjects not considered to be at risk by history or baseline spirometry tested positive. Before the 1984 Olympic games, of 597 members of the US team, 67 (11%) were found to have EIA. Remarkably, only 26 had been previously identified, emphasizing the importance of screening for EIA even in well-conditioned individuals who appear to be in excellent health. The severity of bronchospasm in EIA is related to the level of ventilation, to heat and water loss from the respiratory tree, and also to the rate of airway rewarming and rehydration after the challenge. Postexercise decrease in the peak expiratory flow rate of normal children may be as much as 15%; therefore, only a decrease in excess of 15% should be viewed as diagnostic. EIA is usually provoked by a workload sufficient to produce 80% of maximum oxygen consumption; however, in severe asthmatics even minimal exertion may be enough to produce symptoms. Patients with normal lung function at rest may have severe air flow limitation induced by exercise,10 and as many as 50% of patients who are well-controlled with inhaled corticosteroids still exhibit EIA. A challenge of sufficient magnitude will provoke EIA in all patients with asthma. PHARMACOLOGIC THERAPY: Exercise, unlike exposure to allergens, does not produce a long-term increase in airway reactivity. Accordingly, patients whose symptoms manifest only after strenuous activity may be treated prophylactically and do not require continuous therapy. Most asthma medications, even some unconventional ones such as heparin, furosemide, calcium channel blockers, and terfenadine, given before exercise, suppress EIA. McFadden accounts for the efficacy of these disparate classes of drugs by their potential effect on the bronchial vasculature that modulates the cooling and/or rewarming phases of the reaction. Short-acting -agonists provide protection in 80% to 95% of affected individuals with insignificant side effects and have been regarded for many years as first-line therapy. Two long-acting bronchodilators, salmeterol and formoterol, have been found effective in the prevention of EIA.18-21 A single 50-microg dose of salmeterol protects against EIA for 9 hours; its duration appears to wane in the course of daily therapy. Cromolyn sodium is highly effective in 70% to 87% of those diagnosed with EIA and has minimal side effects. Nedocromil sodium provides protection equal to that of cromolyn in children. Children commonly engage in unplanned physical activity and sometimes are not allowed to carry their own medication. Thus, a simple long-acting regimen given at home is likely to be more effective than short-acting drugs that must be administered in a timely manner. Although the 12-hour protection by salmeterol reported by Bronsky et al may not persist with continued use, the 9-hour duration of action is

Prevention of exercise-induced asthma by a natural isomer mixture of beta-carotene.

BACKGROUND: The unicellular alga Dunaliella bardawil was previously shown to contain very high concentrations of beta-carotene composed of equal amounts of the all-trans and 9-cis stereoisomers which differ in their physicochemical features and antioxidative activity. Due to the controversy regarding the beneficial effect of antioxidants on asthma, the acute effects of beta-carotene of Dunaliella was assessed on airway hyperreactivity in patients with exercise-induced asthma (EIA). METHODS: Thirty-eight patients with EIA participated in our study to verify the antioxidative effect. The test was based on the following sequence: baseline pulmonary function, 7 minutes exercise session on a motorized treadmill, 8 minutes rest, 1-week oral random, double-blind supplementation of placebo or 64 mg/day beta-carotene, pulmonary functions at rest, 7 minutes exercise session, 8 minutes rest and again pulmonary functions. RESULTS: All patients given placebo showed a significant postexercise reduction of more than 15% in their forced expiratory volume in one second (FEV1). Of the 38 patients who received a daily dose of 64 mg of beta-carotene for 1 week, 20 (53%) were protected against EIA. CONCLUSIONS: Our results indicate that a daily dose of Dunaliella beta-carotene exerts a protective effect against EIA in some patients most probably through in vivo antioxidative effect.

Proventil HFA provides protection from exercise-induced bronchoconstriction comparable to proventil and ventolin.

INTRODUCTION: During the 1970s, scientists suggested that the growing use of chlorofluorocarbons (CFCs) was contributing to depletion of the stratospheric ozone layer with potentially harmful results. A committee on the ozone layer organized the preparation of the Montreal Protocol. This protocol mandated the cessation of production and use of CFCs by January 1, 1996. The primary exemption to this ban is for the use of CFCs as propellants in metered dose inhalers (MDIs) for the treatment of asthma. Suitable replacement hydrofluoroalkane (HFA) propellants, such as HFA-134a, for use in MDIs have been identified. Albuterol, a selective beta-adrenergic agonist, currently widely available for inhalation asthma therapy, has been reformulated in HFA-134a (Proventil HFA). OBJECTIVE; To compare the efficacy of Proventil HFA to Ventolin, Proventil, and placebo (HFA-134a) MDI in protecting asthmatic patients from exercise-induced bronchoconstriction. METHODS: This was a randomized, single-blind, placebo-controlled, 4-period crossover study of asthmatic patients with documented exercise-induced broncho-constriction. Twenty patients self administered two puffs of either Proventil HFA, Ventolin, Proventil or placebo, from an MDI, 30 minutes prior to performing a standardized exercise challenge at the study site. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 minutes after completion of the exercise challenge. Heart rate and blood pressure were measured just prior to spirometry and a 12-lead ECG was performed 15 minutes after completion of the exercise challenge for measurement of the QT corrected interval. RESULTS: The primary efficacy variable was the smallest percent change from the predose FEV1 following exercise. The smallest percent change from predose FEV1 for Proventil HFA was 2.0 +/- 9.9 SD, similar to the 2.0 +/- 11.4 SD for Ventolin, and the 3.6 +/- 10.2 SD for Proventil. The smallest percent change from predose FEV1 for each of the active treatments was significantly different from placebo, -23.7 +/- 14.5. Twelve of the patients had a > or = 20% fall in FEV1 post-exercise with placebo pretreatment, but only 1, 1, and 0 had > or = 20% FEV1 falls after treatment with Proventil HFA, Ventolin, and Proventil respectively. Changes in heart rate, blood pressure and QT corrected interval were similar for the three active treatments following exercise. CONCLUSIONS: Proventil HFA provides protection against exercise-induced bronchoconstriction comparable to Ventolin and Proventil and protection superior to placebo. Proventil HFA has a safety profile similar to Ventolin when used to prevent exercise-induced bronchoconstriction.

Do voluntary changes in inspiratory-expiratory ratio prevent exercise-induced asthma?

It is often admitted that heat exchange in the airways is a major cause of exercise-induced asthma. Because a decrease in the inspiratory time/expiratory time ratio (TI/TE) decreases these exchanges, we postulated that it might decrease bronchoconstriction as well. Twenty-four asthmatic children, divided into three groups, underwent two exercise provocation tests, 24 hours apart (outdoor running for 6 min). The first test was identical for all the subjects. In the second test, the first group did not receive any instruction concerning breathing pattern. The second group was instructed to adopt equal inspiratory and expiratory times (TI/TE = 1). The third group had to adopt an expiratory time three times longer than inspiratory time (TI/TE = 1/3). The three groups displayed similar pulmonary function tests (FEV1 and FVC), cardiac frequency, and running performances. However, FEV1 significantly improved in the second session. This suggested that familiarization with the task and related psychological factors may influence asthma more than voluntary changes in TI/TE.

Efficacy of laser-acupuncture in the prevention of exercise-induced asthma.

Many asthmatic patients are reluctant to follow the medication schedule prescribed for them and turn to alternative treatment methods. The results of this study indicate that one such method, laser acupuncture, does not prevent exercise-induced asthma.

Effect of yoga training on exercise tolerance in adolescents with childhood asthma.

Forty six young asthmatics with a history of childhood asthma were admitted for yoga training. Effects of training on resting pulmonary functions, exercise capacity, and exercise-induced bronchial lability index were measured. Yoga training resulted in a significant increase in pulmonary function and exercise capacity. A follow-up study spanning two years showed a good response with reduced symptom score and drug requirements in these subjects. It is concluded that yoga training is beneficial for young asthmatics.

Physical conditioning programme for children with bronchial asthma.

Exercise-induced bronchospasm limits physical activity in most asthmatic children. Twelve children with stable chronic asthma were enrolled in a physical conditioning program to improve ventilation mechanics and to promote physical activity. The program consisted of eight weekly sessions of one-and-a-half hours each, followed by three months of weekly swimming lessons. The activities were preceded by a warm-up period and interspersed with rest. Premedication with an aerosol bronchodilator or sodium cromoglycate was allowed before training. Cardiorespiratory status was studied before and after the program. The program was well received by the children with no bronchospasm. Five showed improvement in lung volumes and/or flow rates. Bronchial liability remained the same. The basal heart rate slowed in four children. No significant arrhythmia was detected. With continued practice, cardiorespiratory function might improve further. The program should be incorporated as part of the overall management of bronchial asthma.

Methylxanthines inhibit exercise-induced bronchoconstriction at low serum theophylline concentration and in a dose-dependent fashion.

We studied the relationship between attenuation of exercise-induced bronchoconstriction and serum theophylline concentration in a dose-dependent fashion in 11 patients with mild bronchial asthma. In addition, we investigated the protection of equal amounts of theophylline either dissolved in ethylenediamine or in proxyphylline and diprophylline. At 4 separate study days, the patients received one of the following preparations in a double-blind random order: saline solution, 200 mg of theophylline in 19.9 mg of ethylenediamine (TE200), 351 mg of theophylline in 35 mg of ethylenediamine (TE351), and 200 mg of theophylline in 300 mg of propxyphylline and 300 mg of diprophylline (TPD). Fifteen minutes after the end of infusion, a standardized exercise test during cold air breathing was performed. Before and up to 30 minutes after each test, specific airway resistance and FEV, were determined. Postexertional bronchoconstriction after theophylline was expressed by means of a protection index, a value of 0 or 1 meaning no or full protection, respectively. At mean (SD) serum theophylline concentrations of 6.7 (1.3), 10.1 (1.7), and 6.3 (1.4) mg/L, respectively, TE200, TE351, and TPD for specific airway resistance caused a significant bronchodilation (p less than 0.05) and resulted in mean (SD) protection indices of 0.61 (0.15), 0.82 (0.14), and 0.65 (0.20), respectively, being significantly different from 0 (p less than 0.01). The protective effect of TE200 and TPD was equal and significantly less pronounced as compared to TE351 (p less than 0.01). Therefore, theophylline attenuated exercise-induced bronchoconstriction in a dose-dependent fashion with significant protection at serum concentrations of about 6 mg/L. The effect of intravenous theophylline was independent of the diluents.

Comparison of nifedipine with a new calcium channel blocker, flordipine, in exercise-induced asthma.

Four patients with documented exercise-induced asthma (EIA) were pretreated orally in random, double-blind fashion with the calcium channel blockers nifedipine 20 mg and flordipine 25 and 50 mg and placebo, then subjected to exercise challenge on a cycloergometer. Each patient served as his own control, undergoing exercise challenge with the different pretreatments on 4 separate days. No statistically significant protection from EIA was found with either nifedipine or flordipine.