β<sub>2</sub>-Agonists and Exercise-Induced Asthma
ABSTRACT Beta2-agonists taken immediately before exercise provide significant protection against exercise- induced asthma (EIA) in most patients. However, when they are taken daily, there are some negative aspects regarding severity, control, and recovery from EIA. First, there is a significant minority (15-20%) of asthmatics whose EIA is not prevented by beta2-agonists, even when inhaled corticosteroids are used concomitantly. Second, with daily use, there is a decline in duration of the protective effect of long-acting beta2-agonists. Third, if breakthrough EIA occurs, recovery of lung function is slower in response to a beta2-agonist, and additional doses are often required to achieve pre-exercise values. If a person who takes a beta2-agonist daily experiences problems with exercise, then the physician should consider changing the treatment regimen to achieve better control of EIA. These problems likely result from desensitization of the beta2-receptor on the mast cell, which enhances mediator release, and on the bronchial smooth muscle, which enhances the bronchoconstrictor response and delays recovery from EIA. These effects are reversed within 72 h after cessation of a beta2-agonists. The important clinical question is: Are we actually compromising the beneficial effects of beta2-agonists on the prevention and recovery from EIA by prescribing them daily? Patients with EIA need to ensure that their doses of inhaled corticosteroid or other anti-inflammatory therapy are optimized so that, if necessary, a beta2-agonist can be used intermittently as prophylactic medication with greater confidence in the outcome.
- SourceAvailable from: Bernd Wolfarth
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- "The development of tolerance to the bronchodilator effects of β2-agonists could influence the success of rescue therapy in severe EIA/EIB.74–76 The increased tolerance is associated with downregulation of peripheral β2-receptors and desensitization of the receptors.75 "
ABSTRACT: Asthma is defined as a chronic inflammatory disorder of the airways with bronchial hyperresponsiveness and variable bronchoconstriction, and is one of the most common diseases in childhood and adolescence. Exercise-induced asthma-like symptoms and asthma are also frequently seen in highly trained athletes. Exercise-induced asthma (EIA) and exercise-induced bronchoconstriction (EIB) are found in 8%-10% of healthy school-aged children and in 35% of children with asthma. Highly increased ventilation, inhalation of cold, dry air and air pollutants (eg, chlorine) are thought to be important triggers for EIA and EIB. EIA is often experienced concurrently with vocal cord dysfunction, which needs to be considered during the differential diagnosis. The pharmacological treatment of EIA is similar to the treatment of asthma in nonexercising adolescents. The therapy is based on anti-inflammatory drugs (eg, inhaled glucocorticosteroids) and bronchodilators (eg, β2-agonists). The treatment of EIB is comparable to the treatment of EIA and leukotriene modifiers offer a new and promising treatment option, particularly in EIB. Generally, athletes may not use β2-agonists according to the prohibited list of the World Anti-Doping Agency (WADA). However, the WADA list contains specific β2-agonistic substances that are permitted to be used by inhalation.Open Access Journal of Sports Medicine 01/2013; 4:1-7. DOI:10.2147/OAJSM.S23438
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- "Pharmacotherapy for the treatment of asthma has also revealed much about the mechanism of indirect AHR. Acute use of β2-agonists demonstrates the most potent protective effect on indirect stimuli, likely due to a combination of non-specific functional antagonism of the released mediators causing bronchoconstriction, as well as via β2-receptor-mediated mast cell stabilization (Anderson et al., 2006). However, regular use of β2-agonists, like their effects on direct stimuli, may increase the airway sensitivity to indirect stimuli, decrease the ability of β2-agonists when used acutely to bronchoprotect, and have decreased efficacy when being used to recover from indirect bronchoconstriction (Hancox et al., 2002; Anderson et al., 2006; Haney and Hancox, 2006). "
ABSTRACT: Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either "direct" or "indirect," referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.Frontiers in Physiology 12/2012; 3:460. DOI:10.3389/fphys.2012.00460 · 3.50 Impact Factor
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- "Perception of respiratory symptoms may vary between individuals—some might feel minor changes more than others . Physical activity is an important release of asthma symptoms, revealing exercise-induced bronchoconstriction  , which is widely believed to be related to either airway inflammation  or smooth muscle dysfunction [5– 8]. The primary treatment strategy in airway inflammation should be inhaled steroid ; whereas smooth muscle dysfunction should be treated primarily with inhaled betaagonist . "
ABSTRACT: Background. Asthma experienced during exercise and during the night is based on the presence of airway hyperresponsiveness (AHR). The aim of the present study was to examine whether AHR is a predictor of exercise-induced asthma (EIA) and nighttime symptoms. Material. We included 793 asthmatics subjects with symptoms and a positive asthma test. Results. Mean (SD) FEV1 was 93% (15), 71% had rhinitis, and 62% had atopy. Both EIA and nighttime symptoms were associated with AHR; however, when including other factors of importance in a multivariate analysis, logRDR was eliminated, whereas FEV1% pred (P < .001), smoking (P < .05), atopy (P < .001), sex (P < .001), and treatment (P < .01) were associated with having EIA while dyspnoea (P < .001), cough (P < .001), and eosinophils (P < .01) were associated with frequent night symptoms. The risk of having nighttime awakenings due to asthma was more than twofold higher among those with EIA symptoms than among those without symptoms (OR (CI95%) 2.77 (2.0–3.8) (P < .001)). In Conclusion. EIA and night symptoms are associated with AHR, but other factors of importance eliminated this close association. Night asthma is more closely associated with airway inflammation than AHR.Journal of Allergy 11/2009; 2009(1):378245. DOI:10.1155/2009/378245